Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and increasing Vesicular GABA Transporter expression

Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and increasing Vesicular GABA Transporter expression | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and increasing Vesicular GABA Transporter expression Maria Meseguer-Beltrán, Sandra Sánchez-Sarasúa, Nóra Kerekes, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4484766/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Apr, 2025 Read the published version in Journal of Neuroimmune Pharmacology → Version 1 posted 12 You are reading this latest preprint version Abstract Background : Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome influenced by both genetic and environmental factors. While genetic studies have highlighted catecholamine dysfunction, emerging epidemiological evidence suggest neuroinflammation as a significant trigger. However, understanding the relative contributions of these alterations to ADHD symptomatology remains elusive. Method: This study employed 93 female Swiss mice of the ADHD dopamine deficit model. Dopaminergic lesions were induced via 6-hydroxidopamine (6-OHDA) injection on postnatal day 5. The impact of these lesions during development was examined by comparing young and adult mice (at postnatal day 21 and 90, respectively). We sought to mitigate adult symptoms through abscisic acid (ABA) administration during two-months. Postmortem analyses encompassed the evaluation of neuroinflammation (microglia morphology, NLRP3 inflammasome activation, cytokine expression) and excitatory/inhibitory (E/I) ratio in specific brain regions. Results: Neonatal dopaminergic lesions elicited hyperactivity, impulsivity, increased social interaction in both young and adult females and lesion induce impaired memory in adults. ABA exposure significantly ameliorated hyperactivity, impulsivity, anxiety, hypersensitivity, and social interaction alterations, but not cognitive impairment in adults. In the anterior cingulate cortex (ACC) of young mice dopamine-deficit induced microglia morphology alterations, elevated IL-1β and TNFa expression and reduced Arg1 mRNA levels, along with E/I imbalance. ABA intervention restored microglia morphology, IL-1β expression and enhanced vGAT levels. Conclusions: This study strongly suggest that dopamine deficit induced alteration of microglia and E/I ratio underling distinct ADHD symptoms. Reinstating healthy microglia by anti-inflammatory agents in specific areas emerges as a promising strategy for managing ADHD. 6-OHDA lesion vGAT vGluT1 E/I ratio IL-1ß Arg1 Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigures.docx SupplementaryTables.docx Cite Share Download PDF Status: Published Journal Publication published 16 Apr, 2025 Read the published version in Journal of Neuroimmune Pharmacology → Version 1 posted Editorial decision: Revision requested 05 Aug, 2024 Reviews received at journal 26 Jul, 2024 Reviewers agreed at journal 25 Jul, 2024 Reviewers agreed at journal 23 Jul, 2024 Reviewers agreed at journal 23 Jul, 2024 Reviews received at journal 02 Jul, 2024 Reviewers agreed at journal 25 Jun, 2024 Reviewers agreed at journal 14 Jun, 2024 Reviewers invited by journal 12 Jun, 2024 Editor assigned by journal 08 Jun, 2024 Submission checks completed at journal 28 May, 2024 First submitted to journal 27 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4484766","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":312124699,"identity":"2a81de22-a35c-4dff-b805-19cb15211840","order_by":0,"name":"Maria Meseguer-Beltrán","email":"","orcid":"","institution":"Universitat Jaume I","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Meseguer-Beltrán","suffix":""},{"id":312124701,"identity":"6b93bdda-80c2-4621-9a1c-e87381580f15","order_by":1,"name":"Sandra Sánchez-Sarasúa","email":"","orcid":"","institution":"Universitat Jaume 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While genetic studies have highlighted catecholamine dysfunction, emerging epidemiological evidence suggest neuroinflammation as a significant trigger. However, understanding the relative contributions of these alterations to ADHD symptomatology remains elusive.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e This study employed 93 female Swiss mice of the ADHD dopamine deficit model. Dopaminergic lesions were induced via 6-hydroxidopamine (6-OHDA) injection on postnatal day 5. The impact of these lesions during development was examined by comparing young and adult mice (at postnatal day 21 and 90, respectively). We sought to mitigate adult symptoms through abscisic acid (ABA) administration during two-months. 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