{"paper_id":"87bbfc7a-b12c-4dbc-9f02-dbf8045bfa8e","body_text":"Abstract\nEndometriosis is a gynecological disease affecting 6–10% of women of reproductive age. In addition to gynecologic symptoms, endometriosis is associated with various systemic effects, including inflammation, altered body weight, and behavioral changes. Previous murine studies demonstrate that endometriosis is causally inked to increased pain sensitization, behavioral changes, and low body mass index (BMI). One possible cellular target that may mediate some of these findings is the hypocretin/orexin neurons. This neuronal system plays a role in regulating wakefulness/sleep cycles, pain perception, and appetite. We hypothesize that endometriosis alters activity level of the hypocretin/orexin (Hcrt) neuronal system. Mice underwent endometriosis induction surgeries (endo) or sham surgeries (sham) for the development of the experimental model. Immunocytochemistry was performed on harvested samples from the lateral hypothalamus, and activation levels of Hcrt cells were examined by quantifying the expression of phosphorylation of cAMP-responsive element binding protein (CREB) in these cells after an acute stress in sham and endo mice. Mice with endometriosis had greater Hcrt neurons activation than sham mice. Mice with endometriosis fed with high fat diet showed a lower fat/body weight and fat/lean tissue ratio compared to mice without endometriosis. There was no significant difference in food intake between sham and endometriosis mice. These results demonstrate that endometriosis is associated with low body mass and increased hypocretin/orexin activity, which could be implicated in the behavioral changes and to differences in body composition.\nSimilar content being viewed by others\nAvailability of Data and Material\nAvailable with Ramanaiah Mamillapalli and Hugh Taylor.\nReferences\nGiudice LC. Clinical practice. 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Endocrinology. 2016;157(7):2870–82.\nFunding\nThis work was supported by the NIH U54 HD052668 and Endometriosis Foundation of America AWD0003567.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nEthics Approval\nEthics followed is approved by Yale University.\nConsent for Publication\nAll authors gave consent for publication.\nConflict of Interest\nThe authors declare no competing interests.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nAbout this article\nCite this article\nMamillapalli, R., Dang, T., Habata, S. et al. Activation of Hypocretin Neurons in Endometriosis. Reprod. Sci. 29, 243–249 (2022). https://doi.org/10.1007/s43032-021-00682-4\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s43032-021-00682-4","source_license":"CC0","license_restricted":false}