海马体中的pCREB/BDNF信号通路参与了选择性5-羟色胺再摄取抑制剂对遭受爆炸性创伤性脑损伤的成年雄性大鼠的治疗作用。
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.
作者信息
Fan Xiaolin, Wang Hong, Lv Xiaoqiang, Wang Qi, Yu Boya, Li Xiao, Li Liang, Zhang Yuhao, Ma Ning, Lu Qing, Qian Airong, Gao Junhong
机构信息
Laboratory for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, No. 127 Youyi West Road, Beilin District, Xi'an 710072, China.
Xi'an Key Laboratory of Toxicology and Biological Effect, Institute for Hygiene of Ordnance Industry, Xi'an 710065, China.
出版信息
Brain Sci. 2025 Feb 24;15(3):236. doi: 10.3390/brainsci15030236.
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.
背景
爆炸所致创伤性脑损伤（bTBI）可在急性期和慢性期导致类似抑郁的行为。在创伤性脑损伤（TBI）动物模型中，选择性5-羟色胺再摄取抑制剂（SSRIs）已被证明可通过增加海马体中的血清素（5-HT）和脑源性神经营养因子（BDNF）来显著减轻类似抑郁的行为。然而，SSRIs对bTBI所致抑郁的治疗效果仍不清楚。
目的
因此，本研究旨在探讨SSRIs对bTBI模型中类似抑郁行为的治疗效果。
方法
我们通过使大鼠承受增加的爆炸超压（BOP）并腹腔注射氟西汀和艾司西酞普兰这两种SSRIs药物28天，创建了一个研究轻度TBI的大鼠模型。
结果
在BOP暴露后第14天，接受SSRIs治疗的大鼠表现出类似抑郁行为的减少。这一发现伴随着海马体中5-HT水平的升高以及齿状回中巢蛋白阳性细胞数量的增加。此外，在bTBI后的第7天、第14天和第28天，接受SSRIs治疗的大鼠海马体中磷酸化环磷腺苷反应元件结合蛋白（pCREB）和BDNF蛋白表达增加。
结论
总体而言，我们的研究结果表明，轻度bTBI后SSRIs诱导的类似抑郁行为的恢复与5-HT水平、pCREB和BDNF表达的上调以及海马体中的神经发生有关。
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