{"title":"海马pCREB/BDNF通路参与5-羟色胺再摄取抑制剂对成年雄性大鼠爆炸创伤性脑损伤的治疗作用","authors":"Xiaolin Fan, Hong Wang, Xiaoqiang Lv, Qi Wang, Boya Yu, Xiao Li, Liang Li, Yuhao Zhang, Ning Ma, Qing Lu, Airong Qian, Junhong Gao","doi":"10.3390/brainsci15030236","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Blast traumatic brain injury (bTBI) can result in depression-like behaviors in the acute and chronic phases. SSRIs have been shown to significantly alleviate depression-like behaviors in animal models of traumatic brain injury (TBI) by increasing serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) in the hippocampus. However, the therapeutic effects of SSRIs on depression caused by bTBI remain unclear.</p><p><strong>Objective: </strong>Therefore, this study was aimed at investigating the therapeutic effects of SSRIs on depression-like behaviors in bTBI models.</p><p><strong>Methods: </strong>We created a rat model to study mild TBI by subjecting rats to increased blast overpressures (BOP) and injecting fluoxetine and escitalopram SSRIs intraperitoneally for 28 days.</p><p><strong>Results: </strong>On day 14 post-BOP exposure, rats treated with SSRIs showed decreased depression-like behaviors. This finding was accompanied by higher 5-HT levels in the hippocampus and increased numbers of Nestin-positive cells in the dentate gyrus. Furthermore, rats treated with SSRIs exhibited increased pCREB and BDNF protein expression in the hippocampus on days 7, 14, and 28 after bTBI.</p><p><strong>Conclusions: </strong>Overall, our findings indicate that SSRI-induced recovery from depression-like behaviors after mild bTBI is associated with the upregulation of 5-HT levels, pCREB and BDNF expression, and neurogenesis in the hippocampus.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940387/pdf/","citationCount":"0","resultStr":"{\"title\":\"The pCREB/BDNF Pathway in the Hippocampus Is Involved in the Therapeutic Effect of Selective 5-HT Reuptake Inhibitors in Adult Male Rats Exposed to Blast Traumatic Brain Injury.\",\"authors\":\"Xiaolin Fan, Hong Wang, Xiaoqiang Lv, Qi Wang, Boya Yu, Xiao Li, Liang Li, Yuhao Zhang, Ning Ma, Qing Lu, Airong Qian, Junhong Gao\",\"doi\":\"10.3390/brainsci15030236\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Blast traumatic brain injury (bTBI) can result in depression-like behaviors in the acute and chronic phases. SSRIs have been shown to significantly alleviate depression-like behaviors in animal models of traumatic brain injury (TBI) by increasing serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) in the hippocampus. However, the therapeutic effects of SSRIs on depression caused by bTBI remain unclear.</p><p><strong>Objective: </strong>Therefore, this study was aimed at investigating the therapeutic effects of SSRIs on depression-like behaviors in bTBI models.</p><p><strong>Methods: </strong>We created a rat model to study mild TBI by subjecting rats to increased blast overpressures (BOP) and injecting fluoxetine and escitalopram SSRIs intraperitoneally for 28 days.</p><p><strong>Results: </strong>On day 14 post-BOP exposure, rats treated with SSRIs showed decreased depression-like behaviors. This finding was accompanied by higher 5-HT levels in the hippocampus and increased numbers of Nestin-positive cells in the dentate gyrus. Furthermore, rats treated with SSRIs exhibited increased pCREB and BDNF protein expression in the hippocampus on days 7, 14, and 28 after bTBI.</p><p><strong>Conclusions: </strong>Overall, our findings indicate that SSRI-induced recovery from depression-like behaviors after mild bTBI is associated with the upregulation of 5-HT levels, pCREB and BDNF expression, and neurogenesis in the hippocampus.</p>\",\"PeriodicalId\":9095,\"journal\":{\"name\":\"Brain Sciences\",\"volume\":\"15 3\",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-02-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940387/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/brainsci15030236\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/brainsci15030236","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
The pCREB/BDNF Pathway in the Hippocampus Is Involved in the Therapeutic Effect of Selective 5-HT Reuptake Inhibitors in Adult Male Rats Exposed to Blast Traumatic Brain Injury.
Background: Blast traumatic brain injury (bTBI) can result in depression-like behaviors in the acute and chronic phases. SSRIs have been shown to significantly alleviate depression-like behaviors in animal models of traumatic brain injury (TBI) by increasing serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) in the hippocampus. However, the therapeutic effects of SSRIs on depression caused by bTBI remain unclear.
Objective: Therefore, this study was aimed at investigating the therapeutic effects of SSRIs on depression-like behaviors in bTBI models.
Methods: We created a rat model to study mild TBI by subjecting rats to increased blast overpressures (BOP) and injecting fluoxetine and escitalopram SSRIs intraperitoneally for 28 days.
Results: On day 14 post-BOP exposure, rats treated with SSRIs showed decreased depression-like behaviors. This finding was accompanied by higher 5-HT levels in the hippocampus and increased numbers of Nestin-positive cells in the dentate gyrus. Furthermore, rats treated with SSRIs exhibited increased pCREB and BDNF protein expression in the hippocampus on days 7, 14, and 28 after bTBI.
Conclusions: Overall, our findings indicate that SSRI-induced recovery from depression-like behaviors after mild bTBI is associated with the upregulation of 5-HT levels, pCREB and BDNF expression, and neurogenesis in the hippocampus.
期刊介绍：
Brain Sciences (ISSN 2076-3425) is a peer-reviewed scientific journal that publishes original articles, critical reviews, research notes and short communications in the areas of cognitive neuroscience, developmental neuroscience, molecular and cellular neuroscience, neural engineering, neuroimaging, neurolinguistics, neuropathy, systems neuroscience, and theoretical and computational neuroscience. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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