Effects of physical exercise on adiponectin and BDNF levels in the blood and primary visual cortex: a pilot study

Effects of physical exercise on adiponectin and BDNF levels in the blood and primary visual cortex: a pilot study | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 15 December 2025 V1 Latest version Share on Effects of physical exercise on adiponectin and BDNF levels in the blood and primary visual cortex: a pilot study Authors : Stephen Agadagba , Ying Liang , Kristine Dalton , Suk-yu Yau , and Benjamin Thompson 0000-0002-3902-2712 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176580740.00332606/v1 537 views 96 downloads Contents Abstract Introduction Statistical Analyses Results Discussion Conclusion Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Previous studies have demonstrated that physical exercise can elevate levels of adiponectin and brain-derived neurotrophic factor (BDNF), contributing to enhanced neuroplasticity in the brain, particularly in the hippocampus. However, it remains unclear whether exercise similarly increases these neurotrophic factors in the visual cortex, and whether such changes are detectable in the blood. This pilot study aimed to address this knowledge gap by evaluating whether short-duration exercise protocols can increase adiponectin and BDNF levels in the visual cortex, and whether corresponding changes are reflected in blood. The findings may help identify accessible biomarkers to inform and optimize exercise-based rehabilitation strategies for enhancing visual function. Adolescent wild-type mice were assigned to one of three groups: control (no exercise), intermittent treadmill running (5 min running, 5 min rest, 3 repeats), or continuous running (15 min running) for five consecutive days. Primary visual cortex and serum samples were collected for measurement of adiponectin and BDNF levels using ELISA kits. Continuous exercise significantly increased serum adiponectin levels compared to both the control and intermittent groups, but did not affect adiponectin levels in the primary visual cortex. No significant changes in BDNF levels were observed in either the primary visual cortex or serum across all exercise groups. These preliminary results indicate that continuous exercise enhances serum adiponectin but does not significantly influence BDNF levels in serum or primary visual cortex under these specific conditions. Effects of physical exercise on adiponectin and BDNF levels in the blood and primary visual cortex: a pilot study Stephen K. Agadagba 1 , Ying Liang 1 , Kristine Dalton 1,3 , Suk-Yu Yau 1,2* , and Benjamin Thompson 1,3 1 Centre for Eye and Vision Research Limited, 17W, Hong Kong Science Park, Hong Kong, China 2 Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, China. 3 School of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada. *Correspondence: Suk-Yu Yau [email protected] Keywords: Adiponectin, Brain-derived neurotrophic factor (BDNF), Visual cortex, Blood, Physical Exercise Abstract Previous studies have demonstrated that physical exercise can elevate levels of adiponectin and brain-derived neurotrophic factor (BDNF), contributing to enhanced neuroplasticity in the brain, particularly in the hippocampus. However, it remains unclear whether exercise similarly increases these neurotrophic factors in the visual cortex, and whether such changes are detectable in the blood. This pilot study aimed to address this knowledge gap by evaluating whether short-duration exercise protocols can increase adiponectin and BDNF levels in the visual cortex, and whether corresponding changes are reflected in blood. The findings may help identify accessible biomarkers to inform and optimize exercise-based rehabilitation strategies for enhancing visual function. Adolescent wild-type mice were assigned to one of three groups: control (no exercise), intermittent treadmill running (5 min running, 5 min rest, 3 repeats), or continuous running (15 min running) for five consecutive days. Primary visual cortex and serum samples were collected for measurement of adiponectin and BDNF levels using ELISA kits. Continuous exercise significantly increased serum adiponectin levels compared to both the control and intermittent groups, but did not affect adiponectin levels in the primary visual cortex. No significant changes in BDNF levels were observed in either the primary visual cortex or serum across all exercise groups. These preliminary results indicate that continuous exercise enhances serum adiponectin but does not significantly influence BDNF levels in serum or primary visual cortex under these specific conditions. Introduction Neuroplasticity, the brain’s ability to reorganize its structure and function in response to experience, plays a critical role in neurodevelopment, learning, and memory. Within the visual cortex, this plasticity is particularly robust during early development, a period known as the critical or sensitive period, and diminishes as the brain matures. This decline in neuroplasticity can hinder the recovery of vision following injury or sensory deprivation in adulthood (Frank, 2017). However, recent animal model studies have provided compelling evidence that neuroplasticity in the visual cortex can be modulated beyond the early developmental window. In these models, exercise has emerged as a non-invasive and promising strategy for enhancing visual cortex plasticity (Virathone et al. 2021), suggesting potential applications for improving visual recovery and cognitive function in later life. Exercise-induced benefits for brain health are increasingly well documented, particularly its effects on enhancing cognitive function, emotional well-being, and neuroplasticity (Loprinzi and Frith, 2019). A central mechanism by which exercise promotes brain health is through the upregulation of neurotrophic factors such as brain-derived neurotrophic factor (BDNF). BDNF is critical for neuronal survival, growth, and synaptic plasticity, and its increased expression is associated with enhanced learning, memory, and overall brain plasticity (Marosi and Mattson, 2014;Dinoff et al., 2016). BDNF is synthesized in the brain but can also cross the blood-brain barrier when produced peripherally, particularly after exercise, making it a potent modulator of visual and cognitive function (Marosi and Mattson, 2014). Adiponectin, a hormone predominantly secreted by adipose tissue, also influences brain plasticity. Initially recognized for its role in metabolic regulation, adiponectin has more recently been implicated in brain health due to its anti-inflammatory and neuroprotective properties (Ohashi et al., 2010;Nicolas et al., 2017;Forny-Germano et al., 2018;Kim et al., 2020). The presence of adiponectin receptors in the brain suggests that it may directly affect neuronal function and plasticity (Sun and Liu, 2019). Adiponectin may also work synergistically with BDNF, contributing to exercise-induced enhancements in neuroplasticity, particularly in the visual system (Schön et al., 2019). An important consideration is the mechanism by which generic aerobic exercise, such as treadmill running, can transfer benefits to specific domains like visual cortex plasticity. Unlike task-specific training that combines visual tasks with exercise (Lunghi and Sale, 2015;Zhou et al., 2017), generic aerobic exercise does not provide direct visual input or training. Instead, its effects on the visual cortex are thought to occur through systemic and neurochemical pathways. During aerobic exercise, there is a global increase in cerebral blood flow and enhanced delivery of oxygen and nutrients to the brain, including the visual cortex (Kalogeraki et al., 2016). More importantly, exercise triggers the release of neurotrophic factors such as BDNF and metabolic hormones like adiponectin into the circulation, which can cross the blood-brain barrier and modulate synaptic plasticity across multiple brain regions (Marosi and Mattson, 2014). Animal studies have demonstrated that voluntary running alone, without any visual task, can reduce intracortical inhibition in the primary visual cortex, enhance neuronal responsiveness, and promote ocular dominance plasticity (Kalogeraki et al., 2016). These exercise-induced neurochemical and physiological changes create a permissive environment for plasticity, effectively ”priming” the visual cortex to be more responsive to subsequent visual experience or training (Sale et al., 2014) . This priming effect may explain why some studies combining exercise with visual tasks observe enhanced plasticity, while generic exercise alone may require longer durations or higher intensities to produce measurable functional visual improvements (Abuleil et al., 2022). Different exercise schedules, including aerobic exercise, resistance training, and high-intensity interval training (HIIT), have been shown to differentially modulate BDNF and adiponectin levels (Winter et al., 2007;Basso and Suzuki, 2017). Aerobic exercise, such as running or cycling, is known to be particularly effective at increasing BDNF expression both in animal models and in humans (Dinoff et al., 2016). Studies have shown that aerobic exercise enhances neurogenesis and synaptic plasticity in the hippocampus, which is crucial for memory and learning (Yau et al., 2011;Yau et al., 2014;Liu and Nusslock, 2018). Additionally, voluntary physical exercise alone has been shown to enhance neuroplasticity specifically in the primary visual cortex (V1) of mice, promoting ocular dominance plasticity and preserving juvenile-like plasticity into adulthood (Kalogeraki et al., 2014;Greifzu et al., 2016). Studies have demonstrated that running wheel access enables adult mice to maintain visual cortex plasticity that would otherwise be lost with age, suggesting potential benefits for visual function (Kalogeraki et al., 2014;Kalogeraki et al., 2016). In contrast, resistance training, though less studied in the context of neuroplasticity, has also been found to increase BDNF levels, albeit to a lesser degree than aerobic exercise (Heijnen et al., 2015). Evidence suggests that resistance training may also influence adiponectin levels, potentially contributing to its neuroprotective effects (Nascimento et al., 2015). The benefits of resistance training extend to improved cognitive function, particularly in older adults, where it has been shown to improve insulin sensitivity and reduce inflammation, factors critical for maintaining brain plasticity (Cheng et al., 2022). HIIT, a form of exercise involving brief, intense bursts of activity followed by periods of rest, has garnered attention for its time-efficient benefits on physical and brain health (Campbell et al., 2019). Recent studies suggest that HIIT may lead to more significant increases in BDNF levels compared to moderate-intensity continuous exercise (Hugues et al., 2021). Some research indicates that the high intensity of HIIT may also result in more pronounced increases in adiponectin levels, potentially augmenting its effects on neuroplasticity (Hwang et al., 2023;Jacob et al., 2023). HIIT’s ability to induce rapid and substantial changes in BDNF and adiponectin levels makes it a promising candidate for enhancing visual neuroplasticity (Fuchs and Flügge, 2014;Cadwallader et al., 2023). While the relationship between adiponectin and BDNF in exercise-induced neuroplasticity has been studied in other brain regions, particularly in the hippocampus where exercise has been shown to increase BDNF levels and promote neurogenesis (Yau et al., 2014;Liu and Nusslock, 2018), their potential interaction specifically within the visual cortex remains largely unexplored. Animal studies have shown that different types of exercise can differentially regulate BDNF and adiponectin in the brain and periphery (Vaynman et al., 2004;Matthews et al., 2009). For example, aerobic exercise has been shown to increase BDNF levels in the hippocampus, promoting synaptic plasticity and neurogenesis (Cotman et al., 2007;van Praag, 2008;Bathina and Das, 2015;Cefis et al., 2023). In the visual cortex, BDNF expression is known to be regulated by visual experience and neuronal activity, and plays a critical role in ocular dominance plasticity and synaptic maturation (Huang et al., 1999;Castrén and Antila, 2017). However, whether exercise-induced changes in BDNF can similarly modulate visual cortex function and translate into improvements in visual performance remains to be fully elucidated. Additionally, the timing and intensity of exercise appear to be crucial factors in optimizing the neuroplastic effects of BDNF and adiponectin (Schön et al., 2019;Murawska-Ciałowicz et al., 2021;Ceylan et al., 2023). Research suggests that the peak in BDNF levels following exercise may be transient, and levels typically return to baseline within hours, suggesting that the timing of exercise interventions is critical for maximizing its neuroplastic benefits (Griffin É et al., 2011;de Sousa Fernandes et al., 2020). Similarly, exercise intensity is a key factor in regulating adiponectin levels, with more intense exercise showing greater effects on adiponectin expression (García-Hermoso et al., 2016;Zhang et al., 2023). This raises important considerations for designing exercise interventions aimed at enhancing visual neuroplasticity (Lunghi and Sale, 2015;Abuleil et al., 2022). Clinically, enhancing visual neuroplasticity through non-invasive methods like exercise is a promising strategy, particularly for conditions like amblyopia where recovery of vision is thought to be limited by the capacity for neuroplasticity within the visual cortex (Thompson, 2021). Indeed, studies in animal models have shown that voluntary physical exercise can promote ocular dominance plasticity in adult mice (Kalogeraki et al., 2014) and aid in the recovery from experimentally induced amblyopia (Sansevero et al., 2020). While some research has explored the broader effects of physical activity on ocular health (Agadagba et al., 2025), the potential for exercise to directly impact visual function in complex retinal diseases such as glaucoma and age-related macular degeneration (AMD) by enabling enhanced processing of residual retinal input to the brain remains an active area of investigation (Yihong et al., 2025). The current literature on exercise-induced enhancements of human visual cortex plasticity is notably mixed, as highlighted in a recent review (Abuleil et al., 2022). For example, some studies report a positive effect; Lunghi and Sale observed transient enhancements in visual plasticity for up to two hours following a 10-minute cycling routine (Lunghi and Sale, 2015), and Holzschneider et al reported positive effects on spatial learning after a six-month cycling regimen (Holzschneider et al., 2012). Conversely, other studies have found no significant benefit. Zhou et al. (2017) and Baldwin et al. (2022), using different visual tasks and an intermittent cycling protocol, found no significant enhancement in visual plasticity post-exercise (Zhou et al., 2017;Baldwin et al., 2022;Tan et al., 2025). This discrepancy suggests that the effects of exercise may depend heavily on the specific protocol and the methods used for assessment. Therefore, before the therapeutic potential of exercise can be optimized, it is crucial to first establish the foundational effects of different exercise schedules on key underlying biomarkers. This pilot study was designed to provide a preliminary investigation into how two different, short-duration exercise schedules —continuous versus intermittent running—affect adiponectin and BDNF levels in both the serum and the primary visual cortex of adolescent wild-type mice. By comparing these distinct protocols, we sought to gather initial data to determine whether the pattern of exercise influences the expression of these key biomarkers. The goal was to provide foundational insights that can guide the design of more extensive future studies on the mechanisms through which exercise might modulate visual cortex plasticity. Materials and Methods 2.1. Animals and Experimental Design All experimental procedures were approved and followed the Animal Subjects Ethics Sub-Committee’s guidelines at The Hong Kong Polytechnic University. Eight-weeks-old wild-type C57BL/6J mice were group housed (5 per cage) in a holding room with controlled temperature (22 ± 2 °C) and kept under a 12 h light-dark cycle. Mice were fed with standard chow and water ad libitum and were allowed to habituate to the housing conditions for two weeks before experiments started. Before the start of the two weeks exercise protocol, the mice were randomly exposed to a stationary treadmill for 30min/day for two weeks in order to facilitate mice acclimatization to the treadmill. The exercise intervention consisted of 5 consecutive days of treadmill running (Day 1 through Day 5), as depicted in Figure 1. Following the two-week acclimatization period, the mice were divided into 3 groups, namely control group (n = 5, 30 mins rest in treadmill), intermittent exercise group (n = 5, 5 mins run and 5 mins rest for 30mins), and continuous exercise group (n = 5, 15 mins run and 15 mins rest) (Figure 1). This 5-day exercise protocol was selected as a pilot investigation based on previous studies demonstrating that short-term exercise interventions (3-7 days) can produce detectable changes in peripheral adiponectin levels and acute neuroplasticity markers in rodent models (Kalogeraki et al., 2016;Geng et al., 2019). While longer-duration interventions (4-8 weeks) are typically required to observe robust changes in brain BDNF and sustained functional plasticity (Dinoff et al., 2016), our primary aim was to assess whether different exercise schedules could produce differential acute effects on these biomarkers as a foundational step for future dose-response studies. Several methodological choices warrant explicit justification. Female mice were selected for this study based on evidence that female rodents show heightened sensitivity to exercise-induced biomarker changes and exhibit more consistent responses to short-duration interventions compared to males (Massett et al., 2021). Additionally, female mice demonstrate greater voluntary running activity and may be more responsive to moderate-intensity exercise protocols (Massett et al., 2021). Treadmill running was chosen over voluntary wheel running because it allows precise control over exercise intensity, duration, and schedule, which was critical for comparing intermittent versus continuous paradigms (Feng et al., 2019). The 5-day protocol represents an acute intervention designed to capture immediate biomarker responses. While longer interventions (4-8 weeks) are typically required for sustained BDNF elevations and functional plasticity (Dinoff et al., 2016), shorter protocols (3-7 days) have been shown to produce detectable changes in peripheral adiponectin and acute plasticity markers in rodent models (Kalogeraki et al., 2016). This duration was selected to test whether different exercise schedules produce differential acute biomarker signatures before committing resources to longer-term studies. Adolescent mice (8 weeks old) were chosen because this age corresponds to young adulthood when the visual system retains some plasticity but has passed the critical period, making it a relevant model for adult visual rehabilitation (Kalogeraki et al., 2016). 2.2. Serum and V1 collection 2.2.1. Serum collection Immediately following the completion of the final treadmill exercise session (within 10-15 minutes), all mice were anesthetized with isoflurane and 800-1000 µL of whole blood was collected via cardiac puncture with a 25G needle. This timing was chosen to capture acute post-exercise levels of adiponectin and BDNF. Blood samples were transferred to an Eppendorf tube allowed to coagulate for 15-20 minutes at room temperature. Coagulated blood samples were then centrifuged at 3000 – 4000 rpm for 10 min at 4°C. The clear sera were collected in clean Eppendorf tubes and stored at − 80°C. 2.2.2. Primary visual cortex sample collection Immediately after serum collection, surgical craniotomy was performed and the primary visual cortex (V1) was dissected at the following coordinates, AP: -2.18 mm to -5.20 mm; ML: 2.5 mm to 3.5 mm; DV: 0.5 mm to 1.5 mm (Paxinos and Franklin, 2019). V1 tissues from both brain hemispheres were collected and immediately frozen at −80ºC. 2.2.3. V1 Tissue Homogenization and Protein Extraction Complete RIPA lysis buffer was freshly prepared immediately prior to tissue homogenization by supplementing 1× RIPA lysis buffer (Santa Cruz Biotechnology, United States) with 10 μL each of PMSF solution, sodium orthovanadate solution, and protease inhibitor cocktail per 1 mL of buffer. V1 tissue samples were homogenized in complete RIPA buffer at a ratio of 3 mL buffer per gram of tissue. Tissue homogenization was performed using a PRECELLYS Evolution homogenizer (Bertin Technologies, Rockville, MD, USA) equipped with 2 mL tube adapters. The homogenization parameters were set as follows: 5800 rpm, 2 cycles of 30 seconds each, with a 20-second interval between cycles, and temperature maintained at 4°C throughout the process. Following homogenization, samples were centrifuged at 14,000 × g for 30 minutes at 4°C. The supernatant containing total protein lysate was collected and transferred to fresh microcentrifuge tubes. Protein concentration was determined using a BCA Protein Assay Kit (Merck Millipore, Darmstadt, Germany), and samples were aliquoted and stored at −80°C until ELISA analysis. 2.3. Immunoassays for Adiponectin and BDNF The levels of adiponectin and BDNF in serum and V1 tissue lysates were quantified using commercially available ELISA kits (Adiponectin mouse ELISA Kit, AdipoGen® Life Sciences; Total BDNF Immunoassay, Quantikine™ ELISA, R&D Systems, Inc, USA). For V1 samples, protein lysates prepared as described above were diluted to appropriate concentrations (typically 50-100 μg total protein per well) in the diluent buffer provided with each kit. All samples were run in duplicate following the manufacturer’s instructions. Absorbance was measured at 450 nm using a microplate reader, and concentrations were calculated from standard curves generated with recombinant protein standards provided in the kits. Statistical Analyses The statistical analyses were performed using GraphPad Prism software (version 8), SPSS (version 16) and Origin 2021b (9.85). The normality of the data sets was tested using Shapiro–Wilk’s test (data passed normality test when the probability value or p -value was greater than 0.05). One-way ANOVA was used to compare the levels of adiponectin and BDNF in the three mice groups followed by Fisher’s LSD post-hoc test as appropriate. A p -value less than 0.05 was considered as statistically significant. Data were shown as mean ± SEM. Results A one-way ANOVA was conducted to examine the effect of continuous running exercise on adiponectin levels. The results showed a significant main effect of continuous running exercise, F(2, 12) = 4.11, p = 0.04. Post-hoc pairwise comparisons using Fisher test indicated that serum adiponectin levels significantly increased in the continuous running group compared to the control group, t(12) = 2.25, p = 0.04. Serum adiponectin levels were also significantly higher in the continuous running group compared to the intermittent running group t(12) = 2.66, p = 0.02 (Figure 2 A). The intermittent running group showed no significant change in serum adiponectin levels compared to the control group. All groups showed no significant change ( p > 0.05) in serum BDNF concentration after running. All groups showed no significant change ( p > 0.05) in serum BDNF levels, in primary visual cortex adiponectin levels and BDNF levels, after running (Figure 2 B, Figure 3 A and Figure 3 B). Discussion In this study, we investigated the physiological effects of different exercise schedules on the levels of adiponectin and BDNF in both serum and primary visual cortex using female wild-type C57BL/6J mice model. As a pilot investigation, the goal was to identify whether different exercise schedules (intermittent vs. continuous) produce differential effects on key biomarkers known to modulate neuroplasticity—specifically adiponectin and BDNF—in the primary visual cortex. Understanding the biomarker responses represents a necessary first step before undertaking more resource-intensive studies that directly assess functional visual outcomes such as visual acuity, contrast sensitivity, or behavioural measures of visual plasticity. Our findings indicate that continuous exercise significantly increased serum adiponectin levels compared to control and intermittent exercise groups, while there were no significant alterations in serum or brain BDNF levels across the groups. The significant increase in adiponectin levels observed in the sustained exercise group is consistent with previous findings that sustained physical activity enhances adiponectin secretion (Sallam and Laher, 2016). It is important to emphasize the scope and limitations of this pilot study. While our long-term research goal is to determine whether exercise can enhance visual function, this study focuses exclusively on characterizing biomarker responses—a critical prerequisite for designing future functional studies. Adiponectin and BDNF are well-established mediators of neuroplasticity in other brain regions (Marosi and Mattson, 2014; Nicolas et al., 2017), and our study sought to determine whether exercise modulates these biomarkers specifically in the visual cortex. The finding that continuous exercise increases serum adiponectin—but not visual cortex tissue levels—provides important mechanistic insights that will inform the design of future studies incorporating functional assessments. Direct measurements of visual function (e.g., optomotor response, visual acuity testing, electrophysiological recordings) are essential next steps that were beyond the scope of this foundational biomarker investigation that was conducted using mice with normal vision. 5.1. Physical Exercise and Adiponectin Regulation in Serum and V1 The effect of exercise on serum levels of adiponectin is associated with several factors, including the type and duration of exercise, as well as the physiological state of the individual. Adiponectin is a hormone secreted by adipocytes with anti-inflammatory, insulin-sensitizing, and adipose metabolism-regulating functions (Virathone et al., 2021). Exercise can promote the secretion of adiponectin by enhancing the metabolic activity of adipose tissue and improving the inflammatory state throughout the body (Kalogeraki et al., 2016). While adiponectin has been shown to have neuroprotective effects in brain regions such as the hippocampus (Ohashi et al., 2010;Nicolas et al., 2017;Forny-Germano et al., 2018;Kim et al., 2020), whether changes in adiponectin levels directly impact visual cortex plasticity remains to be determined. Adiponectin receptors (AdipoR1 and AdipoR2) have been implicated in neuronal function and synaptic plasticity in other brain regions (Nicolas et al., 2017;Sun and Liu, 2019). However, the specific role of adiponectin signaling in visual cortex plasticity and visual learning has not been directly demonstrated. Our finding of increased serum adiponectin without corresponding changes in V1 tissue levels suggests that peripheral and central adiponectin regulation may be dissociated, warranting further investigation into the mechanisms by which exercise-induced systemic adiponectin might influence visual function. However, in the present study, physical exercise did not affect adiponectin levels in the primary visual cortex, despite other research showing brain changes from physical activity. This discrepancy may be due to differences in exercise schedules, brain regions, or the specific mechanisms by which adiponectin influences neuroplasticity. While exercise is known to promote neurogenesis and plasticity in areas like the hippocampus (Wagner et al., 2017;El-Sayes et al., 2019), these effects may not extend uniformly across all brain regions, such as the primary visual cortex, where the regulation of adiponectin might be less sensitive to physical activity Interestingly, in the present study, we did not observe significant changes in adiponectin levels in the primary visual centers of the wild-type mice after exercise. This may be due to the fact that adiponectin levels in the cerebrospinal fluid are significantly lower than in serum, and there is no clear correlation between cerebrospinal fluid and serum adiponectin levels (Gao et al., 2014;Wagner et al., 2017;Miranda et al., 2019;Fukuchi et al., 2020;Kaneko and Stryker, 2023;Ceylan et al., 2024). Another explanation is that the complex structure of the brain, may lead to an elevation of adiponectin in certain brain regions, such as the hippocampus (Erickson et al., 2009) or grey matter (Erickson et al., 2010), but not in the primary visual cortex. This suggests that the mechanisms of action of adiponectin in the central nervous system may be more complex and not entirely dependent on serum levels (Thundyil et al., 2012). From the foregoing, physical exercise has potential positive effects on visual acuity and visual plasticity, partly through increasing serum levels of adiponectin. However, the role of adiponectin within the brain, particularly in primary visual centers, is more complex and warrants further investigation. A cautious approach is recommended, focusing on comparing adiponectin levels across different brain regions to assess its potential impact on vision. 5.2. Physical Exercise and BDNF Regulation in Serum and V1 Numerous studies have shown that regular exercise training increases BDNF (brain-derived neurotrophic factor) expression in the central nervous system and peripheral tissues (Neeper et al., 1995;Cotman and Berchtold, 2002;Taliaz et al., 2010;Yarrow et al., 2010). However, our study did not observe any significant changes in BDNF levels across different exercise paradigms. As one of the most widespread neurotrophic factors in vivo, BDNF not only acts on neuronal growth, survival, differentiation, and synaptic plasticity (Ploughman et al., 2007;Yarrow et al., 2010), but also promotes the repair of myelin sheaths and the development of adult somatotrophy (Klein et al., 2011). Similarly, BDNF plays a key role in visual cortex development and maturation, visual neuron survival, and axon growth (Pérez-Navarro et al., 2000;Canton-Martínez et al., 2022;Zhang et al., 2022). Studies have shown that BDNF can promote the excitability and synaptic plasticity of visual cortex neurons, thereby enhancing visual function and improving visual sensitivity (Rojas Vega et al., 2006;Mackay et al., 2017). In both animal models and human subjects, there is a positive correlation between physical exercise and BDNF levels (Ferris et al., 2007;Zoladz et al., 2008). Exercise can increase the expression and release of BDNF, which in turn activates related signaling pathways and induces neuronal survival, axonal growth, and synaptic remodeling in the visual cortex, ultimately enhancing visual function and plasticity (Gómez-Pinilla et al., 2002;Seifert et al., 2010;Laske et al., 2011). In addition, exercise may indirectly affect visual function by modulating neurotransmitters, oxidative stress, and neuroinflammation (Vaynman et al., 2004;Erickson et al., 2011). In contrast, our experimental results did not reveal an effect of exercise on BDNF. One possible explanation is that although exercise can increase BDNF levels, the duration and intensity of exercise are critical factors in eliciting these changes, and the intensity and duration of exercise in this experiment may not have been sufficient to induce significant BDNF changes (Soya et al., 2007;Rasmussen et al., 2009). Peripheral BDNF levels are known to peak immediately post-exercise and can return to baseline within 30-60 minutes (Yarrow et al., 2010;Roeh et al., 2021). While we collected samples within 10-15 minutes of exercise cessation to capture acute responses, individual variation in the timing of peak BDNF release and the rapid clearance kinetics may have contributed to our inability to detect significant changes. Future studies should include multiple time-point measurements (immediately post-exercise, 30 minutes, 1 hour, and 24 hours) to fully characterize the temporal dynamics of exercise-induced biomarker changes in both serum and brain tissue. Most notably, studies showing significant increases in BDNF often use either acute, high-intensity exercise protocols (generally over 30 minutes of vigorous activity) or long-term interventions of 4–8 weeks or more with daily or near-daily sessions (Dinoff et al., 2016; Ceylan et al., 2024). Our 5-day intervention with moderate-intensity exercise represents a pilot investigation into acute schedule-dependent effects and was not designed to produce the sustained BDNF elevations typically observed with chronic training. Additionally, BDNF levels are known to peak immediately post-exercise and decline rapidly (Yarrow et al., 2010;Roeh et al., 2021), and the timing of measurement in our study may not have captured this transient peak. Therefore, the limited duration and moderate intensity of our protocol, combined with potential timing issues, likely contributed to the absence of detectable BDNF increases. Future studies should employ longer intervention periods, vary exercise intensity, and include multiple time-point measurements to establish dose-response relationships and temporal dynamics for both adiponectin and BDNF in the visual cortex. Furthermore, although exercise increases BDNF mRNA and protein levels in skeletal muscle, this muscle-derived BDNF is not readily released into the circulation, where the brain contributes 70-80% of BDNF during exercise (Rasmussen et al., 2009). Therefore, BDNF expression in serum may not accurately reflect the changes in BDNF levels. Moreover, the effect of exercise on the concentration of BDNF in the brain is closely related to a variety of complex genetic factors, such as the Val66Met mutation (Ieraci et al., 2016), APOEε4 allele carriers (Allard et al., 2017), and methyl CpG-binding protein 2 (KhorshidAhmad et al., 2016). Thus, neither serum nor BDNF concentrations in the primary visual cortex may accurately reflect changes in the central nervous system (CNS) levels (Ploughman et al., 2007;Klein et al., 2011). Moreover, a significant difference in our study compared to others is the use of normally-sighted animals rather than visually deprived ones. Research has shown that visual experience strongly influences BDNF expression and synaptic plasticity in the visual cortex, particularly during critical periods of development (Gao et al., 2014;Kaneko and Stryker, 2023). In studies where mice were raised in the dark, visual deprivation was found to enhance BDNF expression and delay plasticity closure, leading to increased neuroplastic responses in the visual cortex (Fukuchi et al., 2020). This effect of BDNF is thought to support adaptive plasticity when sensory input is lacking, which may not be as pronounced in normally-sighted animals since their visual circuits already receive regular stimulation (Miranda et al., 2019;Kaneko and Stryker, 2023). Our use of normally-sighted animals, combined with moderate-intensity exercise, could explain the lack of significant BDNF increases, as BDNF levels may already be near baseline for neuroplasticity due to standard sensory input. This contrasts with findings in visually deprived animals, where BDNF levels may increase more readily under similar conditions, likely due to greater neuroplasticity potential when sensory input is restricted (Miranda et al., 2019). 5.3. Future Directions and Limitations We acknowledge several limitations in our study which, in turn, highlight important avenues for future research. The findings presented here are from a pilot study, intended to provide a preliminary investigation into how short-duration exercise affects specific biomarkers. As such, a primary next step is to expand upon this work by including a wider range of novel parameters. For example, future studies should analyze other myokines, inflammatory markers, or growth factors such as IGF-1 and VEGF, which are also known to be modulated by physical activity (Kwon et al., 2020). Crucially, it will be important to investigate the functional consequences of these biochemical changes on visual plasticity itself, for instance by using in-vivo electrophysiology or behavioral measures of visual function, to bridge the gap between molecular changes and functional outcomes. Building on this foundational work, longitudinal studies are needed to assess the chronic effects of different exercise patterns. The continuous treadmill model employed here offers a feasible framework for future investigations aimed at delineating the complex connections between physical activity, adipose tissue signaling, and metabolic regulation. By assessing adipokine profiles and neurotrophic factors in various mouse models over longer periods, we could not only gain a clearer picture of exercise-induced metabolic and cognitive outcomes but also more directly assess the relationship between exercise and visual function. Furthermore, future research should explore other key variables. It would be beneficial to investigate potential sex differences in exercise-induced changes in adiponectin and BDNF, as hormonal variations between male and female mice could significantly influence these outcomes. Lastly, incorporating dietary manipulations alongside exercise regimens may further illuminate the complex interaction between nutrition, physical activity, and plasticity-related health markers such as adiponectin and BDNF. Together, these expanded investigations will be necessary to build upon our initial findings and to determine the optimal exercise protocols for potentially therapeutic applications. Conclusion This study elucidated the differential impact of continuous versus intermittent physical exercise on serum adiponectin levels in a wild-type C57BL/6J mouse model, highlighting continuous exercise as a potent activator of adiponectin concentration. This finding could inform the ideal exercise strategy for improving visual acuity and enhancing visual plasticity, thereby contributing to improved visual health in various populations. While changes in BDNF levels were not observed, it emphasizes the complexity of the exercise-BDNF relationship that merits further scrutiny. Further investigation into the mechanistic pathways underlying these relationships is crucial. Data Availability All data generated during this study are included in this manuscript. Ethics Statement All experimental procedures were approved and followed the Animal Subjects Ethics Sub-Committee’s guidelines at The Hong Kong Polytechnic University and were carried out in compliance with the Animals (Control of Experiments) Ordinance at Department of Health, Hong Kong SAR (22-110 in DH/HT&A/8/2/8 Pt.4). Authors Contributions SKA, YL, SYY and BT conceptualized the study; SKA and YL carried out the study and acquisition of data. SKA and YL carried out data analysis. SYY and BT supervised the study. SKA wrote the manuscript. YL contributed to the writing of the manuscript. SYY, BT and KD reviewed the manuscript. All authors approved the final version of the manuscript. Funding This project was supported by the InnoHK Initiative and the Hong Kong Special Administrative Region Government. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. References Abuleil, D., Thompson, B., and Dalton, K. (2022). Aerobic Exercise and Human Visual Cortex Neuroplasticity: A Narrative Review. Neural Plast 2022 , 6771999.Agadagba, S.K., Yau, S.Y., Liang, Y., Dalton, K., and Thompson, B. (2025). Bidirectional causality of physical exercise in retinal neuroprotection. Neural Regen Res 20 , 3400-3415.Allard, J.S., Ntekim, O., Johnson, S.P., Ngwa, J.S., Bond, V., Pinder, D., Gillum, R.F., Fungwe, T.V., Kwagyan, J., and Obisesan, T.O. (2017). APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study. Exp Gerontol 87 , 129-136.Baldwin, A.S., Finn, A.E., Green, H.M., Gant, N., and Hess, R.F. (2022). Exercise does not enhance short-term deprivation-induced ocular dominance plasticity: evidence from dichoptic surround suppression. Vision Res 201 , 108123.Basso, J.C., and Suzuki, W.A. (2017). The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review. Brain Plast 2 , 127-152.Bathina, S., and Das, U.N. (2015). Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci 11 , 1164-1178.Cadwallader, C.J., Steiniger, J., Cooper, P.S., Zhou, S.-H., Hendrikse, J., Sumner, R.L., Kirk, I.J., Chong, T.T.J., and Coxon, J.P. (2023). Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex. Scientific Reports 13 , 7491.Campbell, W.W., Kraus, W.E., Powell, K.E., Haskell, W.L., Janz, K.F., Jakicic, J.M., Troiano, R.P., Sprow, K., Torres, A., Piercy, K.L., and Bartlett, D.B. (2019). High-Intensity Interval Training for Cardiometabolic Disease Prevention. Med Sci Sports Exerc 51 , 1220-1226.Canton-Martínez, E., Rentería, I., García-Suárez, P.C., Moncada-Jiménez, J., Machado-Parra, J.P., Lira, F.S., Johnson, D.K., and Jiménez-Maldonado, A. (2022). Concurrent Training Increases Serum Brain-Derived Neurotrophic Factor in Older Adults Regardless of the Exercise Frequency. Front Aging Neurosci 14 , 791698.Castrén, E., and Antila, H. (2017). Neuronal plasticity and neurotrophic factors in drug responses. Molecular Psychiatry 22 , 1085-1095.Cefis, M., Chaney, R., Wirtz, J., Méloux, A., Quirié, A., Leger, C., Prigent-Tessier, A., and Garnier, P. (2023). Molecular mechanisms underlying physical exercise-induced brain BDNF overproduction. Front Mol Neurosci 16 , 1275924.Ceylan, H.İ., Öztürk, M.E., Öztürk, D., Silva, A.F., Albayrak, M., Saygın, Ö., Eken, Ö., Clemente, F.M., and Nobari, H. (2023). Acute effect of moderate and high-intensity interval exercises on asprosin and BDNF levels in inactive normal weight and obese individuals. Scientific Reports 13 , 7040.Ceylan, H.İ., Silva, A.F., Ramirez-Campillo, R., and Murawska-Ciałowicz, E. (2024). Exploring the Effect of Acute and Regular Physical Exercise on Circulating Brain-Derived Neurotrophic Factor Levels in Individuals with Obesity: A Comprehensive Systematic Review and Meta-Analysis. Biology 13 , 323.Cheng, A., Zhao, Z., Liu, H., Yang, J., and Luo, J. (2022). The physiological mechanism and effect of resistance exercise on cognitive function in the elderly people. Front Public Health 10 , 1013734.Cotman, C.W., and Berchtold, N.C. (2002). Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 25 , 295-301.Cotman, C.W., Berchtold, N.C., and Christie, L.A. (2007). Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 30 , 464-472.De Sousa Fernandes, M.S., Ordônio, T.F., Santos, G.C.J., Santos, L.E.R., Calazans, C.T., Gomes, D.A., and Santos, T.M. (2020). Effects of Physical Exercise on Neuroplasticity and Brain Function: A Systematic Review in Human and Animal Studies. Neural Plast 2020 , 8856621.Dinoff, A., Herrmann, N., Swardfager, W., Liu, C.S., Sherman, C., Chan, S., and Lanctôt, K.L. (2016). The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF): A Meta-Analysis. PLoS One 11 , e0163037.El-Sayes, J., Harasym, D., Turco, C.V., Locke, M.B., and Nelson, A.J. (2019). Exercise-Induced Neuroplasticity: A Mechanistic Model and Prospects for Promoting Plasticity. The Neuroscientist 25 , 65-85.Erickson, K.I., Prakash, R.S., Voss, M.W., Chaddock, L., Hu, L., Morris, K.S., White, S.M., Wójcicki, T.R., Mcauley, E., and Kramer, A.F. (2009). Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus 19 , 1030-1039.Erickson, K.I., Raji, C.A., Lopez, O.L., Becker, J.T., Rosano, C., Newman, A.B., Gach, H.M., Thompson, P.M., Ho, A.J., and Kuller, L.H. (2010). Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study. Neurology 75 , 1415-1422.Erickson, K.I., Voss, M.W., Prakash, R.S., Basak, C., Szabo, A., Chaddock, L., Kim, J.S., Heo, S., Alves, H., White, S.M., Wojcicki, T.R., Mailey, E., Vieira, V.J., Martin, S.A., Pence, B.D., Woods, J.A., Mcauley, E., and Kramer, A.F. (2011). Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A 108 , 3017-3022.Feng, R., Wang, L., Li, Z., Yang, R., Liang, Y., Sun, Y., Yu, Q., Ghartey-Kwansah, G., Sun, Y., Wu, Y., Zhang, W., Zhou, X., Xu, M., Bryant, J., Yan, G., Isaacs, W., Ma, J., and Xu, X. (2019). A systematic comparison of exercise training protocols on animal models of cardiovascular capacity. Life Sci 217 , 128-140.Ferris, L.T., Williams, J.S., and Shen, C.L. (2007). The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc 39 , 728-734.Forny-Germano, L., De Felice, F.G., and Vieira, M. (2018). The Role of Leptin and Adiponectin in Obesity-Associated Cognitive Decline and Alzheimer’s Disease. Front Neurosci 12 , 1027.Frank, M.G. (2017). Sleep and plasticity in the visual cortex: more than meets the eye. Curr Opin Neurobiol 44 , 8-12.Fuchs, E., and Flügge, G. (2014). Adult neuroplasticity: more than 40 years of research. Neural Plast 2014 , 541870.Fukuchi, M., Saito, R., Maki, S., Hagiwara, N., Nakajima, Y., Mitazaki, S., Izumi, H., and Mori, H. (2020). Visualization of activity-regulated BDNF expression in the living mouse brain using non-invasive near-infrared bioluminescence imaging. Molecular Brain 13 , 122.Gao, M., Maynard, K.R., Chokshi, V., Song, L., Jacobs, C., Wang, H., Tran, T., Martinowich, K., and Lee, H.-K. (2014). Rebound Potentiation of Inhibition in Juvenile Visual Cortex Requires Vision-Induced BDNF Expression. The Journal of Neuroscience 34 , 10770-10779.García-Hermoso, A., Ceballos-Ceballos, R.J.M., Poblete-Aro, C.E., Hackney, A.C., Mota, J., and Ramírez-Vélez, R. (2016). Exercise, adipokines and pediatric obesity: a meta-analysis of randomized controlled trials. Geng, L., Liao, B., Jin, L., Huang, Z., Triggle, C.R., Ding, H., Zhang, J., Huang, Y., Lin, Z., and Xu, A. (2019). Exercise Alleviates Obesity-Induced Metabolic Dysfunction via Enhancing FGF21 Sensitivity in Adipose Tissues. Cell Rep 26 , 2738-2752.e2734.Gómez-Pinilla, F., Ying, Z., Roy, R.R., Molteni, R., and Edgerton, V.R. (2002). Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol 88 , 2187-2195.Greifzu, F., Kalogeraki, E., and Löwel, S. (2016). Environmental enrichment preserved lifelong ocular dominance plasticity, but did not improve visual abilities. Neurobiol Aging 41 , 130-137.Griffin É, W., Mullally, S., Foley, C., Warmington, S.A., O’mara, S.M., and Kelly, A.M. (2011). Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males. Physiol Behav 104 , 934-941.Heijnen, S., Hommel, B., Kibele, A., and Colzato, L.S. (2015). Neuromodulation of Aerobic Exercise-A Review. Front Psychol 6 , 1890.Holzschneider, K., Wolbers, T., Röder, B., and Hötting, K. (2012). Cardiovascular fitness modulates brain activation associated with spatial learning. Neuroimage 59 , 3003-3014.Huang, Z.J., Kirkwood, A., Pizzorusso, T., Porciatti, V., Morales, B., Bear, M.F., Maffei, L., and Tonegawa, S. (1999). BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell 98 , 739-755.Hugues, N., Pellegrino, C., Rivera, C., Berton, E., Pin-Barre, C., and Laurin, J. (2021). Is High-Intensity Interval Training Suitable to Promote Neuroplasticity and Cognitive Functions after Stroke? Int J Mol Sci 22.Hwang, D.-J., Um, H.-S., Choi, D.-H., and Cho, J.-Y. (2023). Neuroprotective Effects of High-Intensity Interval Training through Neuroplastic Changes in a Restraint Stress-Induced Depression Model. Applied Sciences 13 , 7680.Ieraci, A., Madaio, A.I., Mallei, A., Lee, F.S., and Popoli, M. (2016). Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice. Neuropsychopharmacology 41 , 3070-3079.Jacob, N., So, I., Sharma, B., Marzolini, S., Tartaglia, M.C., Oh, P., and Green, R. (2023). Effects of High-Intensity Interval Training Protocols on Blood Lactate Levels and Cognition in Healthy Adults: Systematic Review and Meta-Regression. Sports Med 53 , 977-991.Kalogeraki, E., Greifzu, F., Haack, F., and Löwel, S. (2014). Voluntary physical exercise promotes ocular dominance plasticity in adult mouse primary visual cortex. J Neurosci 34 , 15476-15481.Kalogeraki, E., Pielecka-Fortuna, J., Hüppe, J.M., and Löwel, S. (2016). Physical Exercise Preserves Adult Visual Plasticity in Mice and Restores it after a Stroke in the Somatosensory Cortex. Front Aging Neurosci 8 , 212.Kaneko, M., and Stryker, M.P. (2023). Production of brain-derived neurotrophic factor gates plasticity in developing visual cortex. Proc Natl Acad Sci U S A 120 , e2214833120.Khorshidahmad, T., Acosta, C., Cortes, C., Lakowski, T.M., Gangadaran, S., and Namaka, M. (2016). Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS). Mol Neurobiol 53 , 1092-1107.Kim, J.Y., Barua, S., Jeong, Y.J., and Lee, J.E. (2020). Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer’s Disease. International Journal of Molecular Sciences 21 , 6419.Klein, A.B., Williamson, R., Santini, M.A., Clemmensen, C., Ettrup, A., Rios, M., Knudsen, G.M., and Aznar, S. (2011). Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol 14 , 347-353.Kwon, J.H., Moon, K.M., and Min, K.W. (2020). Exercise-Induced Myokines can Explain the Importance of Physical Activity in the Elderly: An Overview. Healthcare (Basel) 8.Laske, C., Stellos, K., Hoffmann, N., Stransky, E., Straten, G., Eschweiler, G.W., and Leyhe, T. (2011). Higher BDNF serum levels predict slower cognitive decline in Alzheimer’s disease patients. Int J Neuropsychopharmacol 14 , 399-404.Liu, P.Z., and Nusslock, R. (2018). Exercise-Mediated Neurogenesis in the Hippocampus via BDNF. Front Neurosci 12 , 52.Loprinzi, P.D., and Frith, E. (2019). A brief primer on the mediational role of BDNF in the exercise-memory link. Clin Physiol Funct Imaging 39 , 9-14.Lunghi, C., and Sale, A. (2015). A cycling lane for brain rewiring. Curr Biol 25 , R1122-1123.Mackay, C.P., Kuys, S.S., and Brauer, S.G. (2017). The Effect of Aerobic Exercise on Brain-Derived Neurotrophic Factor in People with Neurological Disorders: A Systematic Review and Meta-Analysis. Neural Plast 2017 , 4716197.Marosi, K., and Mattson, M.P. (2014). BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab 25 , 89-98.Massett, M.P., Matejka, C., and Kim, H. (2021). Systematic Review and Meta-Analysis of Endurance Exercise Training Protocols for Mice. Front Physiol 12 , 782695.Matthews, V.B., Aström, M.B., Chan, M.H., Bruce, C.R., Krabbe, K.S., Prelovsek, O., Akerström, T., Yfanti, C., Broholm, C., Mortensen, O.H., Penkowa, M., Hojman, P., Zankari, A., Watt, M.J., Bruunsgaard, H., Pedersen, B.K., and Febbraio, M.A. (2009). Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia 52 , 1409-1418.Miranda, M., Morici, J.F., Zanoni, M.B., and Bekinschtein, P. (2019). Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain. Front Cell Neurosci 13 , 363.Murawska-Ciałowicz, E., De Assis, G.G., Clemente, F.M., Feito, Y., Stastny, P., Zuwała-Jagiełło, J., Bibrowicz, B., and Wolański, P. (2021). Effect of four different forms of high intensity training on BDNF response to Wingate and Graded Exercise Test. Sci Rep 11 , 8599.Nascimento, C.M., Pereira, J.R., Pires De Andrade, L., Garuffi, M., Ayan, C., Kerr, D.S., Talib, L.L., Cominetti, M.R., and Stella, F. (2015). Physical exercise improves peripheral BDNF levels and cognitive functions in mild cognitive impairment elderly with different bdnf Val66Met genotypes. J Alzheimers Dis 43 , 81-91.Neeper, S.A., Gómez-Pinilla, F., Choi, J., and Cotman, C. (1995). Exercise and brain neurotrophins. Nature 373 , 109.Nicolas, S., Cazareth, J., Zarif, H., Guyon, A., Heurteaux, C., Chabry, J., and Petit-Paitel, A. (2017). Globular Adiponectin Limits Microglia Pro-Inflammatory Phenotype through an AdipoR1/NF-κB Signaling Pathway. Front Cell Neurosci 11 , 352.Ohashi, K., Parker, J.L., Ouchi, N., Higuchi, A., Vita, J.A., Gokce, N., Pedersen, A.A., Kalthoff, C., Tullin, S., Sams, A., Summer, R., and Walsh, K. (2010). Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem 285 , 6153-6160.Paxinos, G., and Franklin, K.B. (2019). Paxinos and Franklin’s the mouse brain in stereotaxic coordinates. Academic press.Pérez-Navarro, E., Canudas, A.M., Akerund, P., Alberch, J., and Arenas, E. (2000). Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 prevent the death of striatal projection neurons in a rodent model of Huntington’s disease. J Neurochem 75 , 2190-2199.Ploughman, M., Granter-Button, S., Chernenko, G., Attwood, Z., Tucker, B.A., Mearow, K.M., and Corbett, D. (2007). Exercise intensity influences the temporal profile of growth factors involved in neuronal plasticity following focal ischemia. Brain Res 1150 , 207-216.Rasmussen, P., Brassard, P., Adser, H., Pedersen, M.V., Leick, L., Hart, E., Secher, N.H., Pedersen, B.K., and Pilegaard, H. (2009). Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 94 , 1062-1069.Roeh, A., Holdenrieder, S., Schoenfeld, J., Haeckert, J., Halle, M., Falkai, P., Scherr, J., and Hasan, A. (2021). Decreased Serum Brain-Derived Neurotrophic Factor Concentrations 72 Hours Following Marathon Running. Front Physiol 12 , 668454.Rojas Vega, S., Strüder, H.K., Vera Wahrmann, B., Schmidt, A., Bloch, W., and Hollmann, W. (2006). Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans. Brain Res 1121 , 59-65.Sale, A., Berardi, N., and Maffei, L. (2014). Environment and brain plasticity: towards an endogenous pharmacotherapy. Physiol Rev 94 , 189-234.Sallam, N., and Laher, I. (2016). Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases. Oxidative Medicine and Cellular Longevity 2016 , 7239639.Sansevero, G., Torelli, C., Mazziotti, R., Consorti, A., Pizzorusso, T., Berardi, N., and Sale, A. (2020). Running towards amblyopia recovery. Scientific Reports 10 , 12661.Schön, M., Kovaničová, Z., Košutzká, Z., Nemec, M., Tomková, M., Jacková, L., Máderová, D., Slobodová, L., Valkovič, P., Ukropec, J., and Ukropcová, B. (2019). Effects of running on adiponectin, insulin and cytokines in cerebrospinal fluid in healthy young individuals. Scientific Reports 9 , 1959.Seifert, T., Brassard, P., Wissenberg, M., Rasmussen, P., Nordby, P., Stallknecht, B., Adser, H., Jakobsen, A.H., Pilegaard, H., Nielsen, H.B., and Secher, N.H. (2010). Endurance training enhances BDNF release from the human brain. Am J Physiol Regul Integr Comp Physiol 298 , R372-377.Soya, H., Nakamura, T., Deocaris, C.C., Kimpara, A., Iimura, M., Fujikawa, T., Chang, H., Mcewen, B.S., and Nishijima, T. (2007). BDNF induction with mild exercise in the rat hippocampus. Biochem Biophys Res Commun 358 , 961-967.Sun, L.N., and Liu, X.L. (2019). Functions of adiponectin signaling in regulating neural plasticity and its application as the therapeutic target to neurological and psychiatric diseases. Rev Neurosci 30 , 485-495.Taliaz, D., Stall, N., Dar, D.E., and Zangen, A. (2010). Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol Psychiatry 15 , 80-92.Tan, K.W.S., Stalin, A., Park, A.S.Y., Dalton, K., and Thompson, B. (2025). Interleaved periods of exercise do not enhance visual perceptual learning. J Vis 25 , 5.Thompson, B. (2021). ”Neural Plasticity in Amblyopia”. Oxford University Press).Thundyil, J., Pavlovski, D., Sobey, C.G., and Arumugam, T.V. (2012). Adiponectin receptor signalling in the brain. Br J Pharmacol 165 , 313-327.Van Praag, H. (2008). Neurogenesis and exercise: past and future directions. Neuromolecular Med 10 , 128-140.Vaynman, S., Ying, Z., and Gomez-Pinilla, F. (2004). Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20 , 2580-2590.Virathone, L., Nguyen, B.N., Dobson, F., Carter, O.L., and Mckendrick, A.M. (2021). Exercise alone impacts short-term adult visual neuroplasticity in a monocular deprivation paradigm. J Vis 21 , 12.Wagner, G., Herbsleb, M., De La Cruz, F., Schumann, A., Köhler, S., Puta, C., Gabriel, H.W., Reichenbach, J.R., and Bär, K.J. (2017). Changes in fMRI activation in anterior hippocampus and motor cortex during memory retrieval after an intense exercise intervention. Biol Psychol 124 , 65-78.Winter, B., Breitenstein, C., Mooren, F.C., Voelker, K., Fobker, M., Lechtermann, A., Krueger, K., Fromme, A., Korsukewitz, C., Floel, A., and Knecht, S. (2007). High impact running improves learning. Neurobiol Learn Mem 87 , 597-609.Yarrow, J.F., White, L.J., Mccoy, S.C., and Borst, S.E. (2010). Training augments resistance exercise induced elevation of circulating brain derived neurotrophic factor (BDNF). Neurosci Lett 479 , 161-165.Yau, S.Y., Lau, B.W., Tong, J.B., Wong, R., Ching, Y.P., Qiu, G., Tang, S.W., Lee, T.M., and So, K.F. (2011). Hippocampal neurogenesis and dendritic plasticity support running-improved spatial learning and depression-like behaviour in stressed rats. PLoS One 6 , e24263.Yau, S.Y., Li, A., Hoo, R.L., Ching, Y.P., Christie, B.R., Lee, T.M., Xu, A., and So, K.F. (2014). Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin. Proc Natl Acad Sci U S A 111 , 15810-15815.Yihong, P., Thompson, B., Winser, S., Lau, I., Suen, V., Cheung, M., and Cheong, A.M.Y. (2025). Glaucoma rehabilitation with action video games and exercise: study protocol of an active-controlled trial (GRADE). BMJ Open 15 , e105971.Zhang, S., Zhen, K., Su, Q., Chen, Y., Lv, Y., and Yu, L. (2022). The Effect of Aerobic Exercise on Cognitive Function in People with Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Environ Res Public Health 19.Zhang, Y., Wu, Y., Fei, X., Li, Y., Li, Y., and Yan, X. (2023). Effects of Aerobic Exercise on Serum Adiponectin Concentrations in Children and Adolescents with Obesity: A Systematic Review and Meta-Analysis. Life 13 , 1772.Zhou, J., Reynaud, A., and Hess, R.F. (2017). Aerobic Exercise Effects on Ocular Dominance Plasticity with a Phase Combination Task in Human Adults. Neural Plast 2017 , 4780876.Zoladz, J.A., Pilc, A., Majerczak, J., Grandys, M., Zapart-Bukowska, J., and Duda, K. (2008). Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men. J Physiol Pharmacol 59 Suppl 7 , 119-132. Figure Captions Figure 1: Experimental timeline. After a 14-day acclimatization, each mouse was exposed to the treadmill for 30 mins daily for 14 days. The treadmill running protocol (18 m/min, 5 days) was then initiated with 15 female C57BL/6J mice were randomly divided into three groups: control (n=5, rested on the treadmill for 30 mins), intermittent exercise (n=5, ran for 5 mins and rested for 5 mins over 30 mins), and continuous exercise (n=5, ran for 15 mins and rested for 15 mins). Figure 2: Adiponectin concentration in the serum and primary visual cortex. (A). The continuous running group showed a significant increase in serum adiponectin levels compared to the control group (* P = 0.04). Serum adiponectin levels were also significantly higher in the continuous running group compared to the intermittent running group (**P= 0.02). The intermittent running group showed no significant change in serum adiponectin levels compared to the control group. (Control group: rested on the treadmill for 30 mins; Intermittent running group: ran for 5 mins and rested for 5 mins for 3 rounds, totalling 30 mins; Continuous running group: ran for 15 mins and rested for 15 mins). (B). All groups showed no significant change (P > 0.05) in primary visual cortex adiponectin levels after running. (Control group: rested on the treadmill for 30 mins; Intermittent running group: ran for 5 mins and rested for 5 mins for 3 rounds, totaling 30 mins; Continuous running group: ran for 15 mins and rested for 15 mins). Figure 3: The BDNF concentration in the serum and primary visual cortex. (A). All groups showed no significant change (P > 0.05) in serum BDNF concentration after running. (Control group: rested on the treadmill for 30 mins; Intermittent running group: ran for 5 mins and rested for 5 mins for 3 rounds, totaling 30 mins; Continuous running group: ran for 15 mins and rested for 15 mins). (B). All groups showed no significant change ( P > 0.05) in primary visual cortex BDNF concentration after running. (Control group: rested on the treadmill for 30 mins; Intermittent running group: ran for 5 mins and rested for 5 mins for 3 rounds, totaling 30 mins; Continuous running group: ran for 15 mins and rested for 15 mins). Information & Authors Information Version history V1 Version 1 15 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords neuroplasticity neurotransmitter rodent models vision Authors Affiliations Stephen Agadagba Centre for Eye and Vision Research Limited View all articles by this author Ying Liang Centre for Eye and Vision Research Limited View all articles by this author Kristine Dalton University of Waterloo View all articles by this author Suk-yu Yau Centre for Eye and Vision Research Limited View all articles by this author Benjamin Thompson 0000-0002-3902-2712 [email protected] The University of Waterloo View all articles by this author Metrics & Citations Metrics Article Usage 537 views 96 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Stephen Agadagba, Ying Liang, Kristine Dalton, et al. Effects of physical exercise on adiponectin and BDNF levels in the blood and primary visual cortex: a pilot study. Authorea . 15 December 2025. 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