Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China.
Department of Physiology, Shanxi Medical University, Taiyuan 030001, PR China.
Behav Brain Res. 2019 Jun 3;365:150-156. doi: 10.1016/j.bbr.2019.03.010. Epub 2019 Mar 6.
Chronic stressor induces the release of glucocorticoid from the adrenal glands, the subsequent decrease of hippocampal volume, and the development of depression. Brain-derived neurotrophic factor (BDNF), composed of mature BDNF (mBDNF) and proBDNF, plays opposite roles in the structural integrity of the brain. However, the underlying mechanism of glucocorticoid-induced hippocampal atrophy remains unclear. Using the open field test, sucrose preference test, elevated plus maze test, and forced swimming test, we observed that the chronic (3 w) administration of corticosterone (CORT) (50 μg/ml) induced depressive-like behaviors in rats. Next, using Western blot assay, we showed that CORT exposure increased the proBDNF level in the ventral hippocampal dentate gyrus (DG), decreased the mBDNF level in the dorsal and ventral DG, and decreased the mBDNF/proBDNF ratio in the hippocampal DG. Furthermore, CORT administration differentially altered the expression of 11 Bdnf mRNA transcripts in the dorsal and ventral hippocampal DG. Our findings suggest an essential role for the mBDNF-proBDNF system in regulating the hippocampus of CORT-treated rats and present a new therapeutic mechanism for antidepressant treatments by targeting the Bdnf mRNA transcripts.
慢性应激源会导致肾上腺释放糖皮质激素，随后海马体体积减小，发展为抑郁症。脑源性神经营养因子（BDNF）由成熟 BDNF（mBDNF）和前体 BDNF（proBDNF）组成，在大脑结构完整性方面发挥着相反的作用。然而，糖皮质激素诱导海马体萎缩的潜在机制尚不清楚。通过旷场实验、蔗糖偏好实验、高架十字迷宫实验和强迫游泳实验，我们观察到慢性（3 周）给予皮质酮（CORT）（50μg/ml）可诱导大鼠出现抑郁样行为。接下来，通过 Western blot 分析，我们发现 CORT 暴露增加了腹侧海马齿状回（DG）中的 proBDNF 水平，降低了背侧和腹侧 DG 中的 mBDNF 水平，并降低了海马 DG 中的 mBDNF/proBDNF 比值。此外，CORT 给药还改变了背侧和腹侧海马 DG 中 11 种 Bdnf mRNA 转录本的表达。我们的研究结果表明，mBDNF-proBDNF 系统在调节 CORT 处理大鼠的海马体方面起着重要作用，并为针对 Bdnf mRNA 转录本的抗抑郁治疗提供了新的治疗机制。
