Peritoneal endometriosis induces time-related depressive- and anxiety-like alterations in female rats: involvement of hippocampal pro-oxidative and BDNF alterations

Endometriosis is a gynecological condition affecting 10% of women in reproductive age. High rates of depression and anxiety are observed in these patients. The mechanisms underlying endometriosis-induced behavioral alterations are still elusive. Animal models provide a useful tool to study the temporal sequence and biological pathways involved in this disease and comorbid states. Here, we sought to characterize time-related behavioral alterations in rats submitted to endometriosis model (EM) induced by peritoneal auto-transplantation of uterine tissues weekly for three weeks. Corticosterone stress reactivity, oxidative stress markers – reduced glutathione (GSH), lipid peroxidation, activity of superoxide dismutase (SOD) and myeloperoxidase (MPO) - and brain-derived-neurotrophic factor (BDNF) levels in the hippocampus were also evaluated. We observed a progressive increase in anxiety-like behavior from 14th to 21st days post-EM. Despair-like behavior was observed from the 14th day post-EM on, while anhedonia and apathetic-like behaviors accompanied by increased corticosterone stress response were detected on 21 days post-EM. Increased pain sensitivity was observed from the 7th day post-EM and was accompanied by increased endometrioma weight. The pro-oxidative alterations, decreased GSH and increased SOD activity were observed on 21 days post-EM, except for lipid peroxidation that was altered from the 14th day. Decreased BDNF also occurred on the 21st day. Therefore, this study demonstrates that EM is related to several features of clinical depression and proposes the contribution of hippocampal oxidative state and neurotrophic support for the emergence of these changes. Our results support the use of this model as a useful tool to test new strategies for endometriosis-related neuropsychiatric symptoms. Similar content being viewed by others

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The authors thank Ms. Maria Vilani for technical support. Role of funding source This work was partially supported by CNPq and CAPES. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest for the present investigation. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Paulo Wagner Linhares Lima Filho and Adriano José Maia Chaves Filho should be considered co-first authors Highlights - Endometriosis model (EM) is related to several features of clinical depression; - EM causes progressive increases in anxiety-like behavior; - Behavioral alterations followed the cystic growth of endometriosis lesions; - Hippocampal oxidative and neurotrophic changes underlie EM behavioral alterations Rights and permissions About this article Cite this article Filho, P.W.L.L., Chaves Filho, A.J.M., Vieira, C.F.X. et al. Peritoneal endometriosis induces time-related depressive- and anxiety-like alterations in female rats: involvement of hippocampal pro-oxidative and BDNF alterations. Metab Brain Dis 34, 909–925 (2019). https://doi.org/10.1007/s11011-019-00397-1 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11011-019-00397-1