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Despite its significance, reserpine\u2019s neuroendocrine toxicity remains largely underexplored. Here, we investigated the effects of reserpine on development, locomotion, central nervous system (CNS) neurons, thyroid development, and the expression of genes related to neurodevelopment, endocrine, learning and memory, and depression in zebrafish exposed to different doses of reserpine ranging from 0.5 mg\/L to 16 mg\/L. The results of our study demonstrated that reserpine exerts dose-dependent toxicity on the neuroendocrine system (NES). An investigation into its underlying mechanism suggests that reserpine disrupted the hypothalamic\u2013pituitary\u2013thyroid (HPT) axis via down-regulating hhex, tg, and tsh\u03b2 genes, impairing thyroid hormone synthesis and endocrine balance. Meanwhile, it affected neurodevelopment, as evidenced by the reduced expression of gfap, gap43, mbp, syn2a, and tuba1b genes, which compromised neuronal structure and function, while impaired neurotransmitter release and uptake could occur due to the suppression of crhb and mao genes. To conclude, these findings illustrate the interconnected impact of pathways involved in endocrine and neurodevelopment in reserpine-induced toxicity.<\/jats:p>","DOI":"10.3390\/neurosci6020028","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T11:08:40Z","timestamp":1743505720000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Reserpine Causes Neuroendocrine Toxicity, Inducing Impairments in Cognition via Disturbing Hypothalamic\u2013Pituitary\u2013Thyroid Axis in Zebrafish"],"prefix":"10.3390","volume":"6","author":[{"given":"Fengzhi","family":"Sun","sequence":"first","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji\u2019nan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji\u2019nan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Xia","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji\u2019nan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji\u2019nan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baokun","family":"Wang","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji\u2019nan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji\u2019nan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanao","family":"Liu","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji\u2019nan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji\u2019nan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Cui","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji\u2019nan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji\u2019nan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Kang","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji\u2019nan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji\u2019nan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-2187","authenticated-orcid":false,"given":"Rostyslav","family":"Stoika","sequence":"additional","affiliation":[{"name":"Department of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology, National Academy of Sciences of Ukraine, 16, Drahomanov Street 14, 79005 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kechun","family":"Liu","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji\u2019nan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji\u2019nan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1525-0876","authenticated-orcid":false,"given":"Meng","family":"Jin","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji\u2019nan 250103, China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji\u2019nan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1007\/s11011-021-00789-2","article-title":"Reserpine-induced altered neuro-behavioral, biochemical and histopathological assessments prevent by enhanced antioxidant defence system of thymoquinone in mice","volume":"36","author":"Samad","year":"2021","journal-title":"Metab. 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