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抑郁习得无助模型大鼠海马 CA1 和 CA3 区中紧密连接蛋白-5 和水通道蛋白-4 的减少。

Reduction of claudin-5 and aquaporin-4 in the rat hippocampal CA-1 and CA-3 regions of a learned helplessness model of depression.

机构信息

Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba 260-8670, Japan.

Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba 260-8670, Japan.

出版信息

Pharmacol Biochem Behav. 2024 Jan;234:173676. doi: 10.1016/j.pbb.2023.173676. Epub 2023 Nov 21.

Abstract

BACKGROUND

Although findings from both animal and clinical research indicate that the blood-brain barrier (BBB) contributes to the pathogenesis of various psychiatric disorders (including depression), the underlying mechanisms are unknown. We investigated the levels of the tight-junction proteins claudin-5 and aquaporin-4 (AQP-4) in astrocytes of learned helplessness (LH) rats (an animal model of depression) and non-LH rats (a model of resilience).

METHODS

We administered inescapable mild electric shock to rats and then identified the LH and non-LH rats by a post-shock test. The expressions of claudin-5 and AQP-4 in several brain regions of the LH and non-LH rats were then evaluated by a western blot analysis.

RESULTS

The levels of both claudin-5 and AQP-4 in the CA-1 and CA-3 hippocampal areas of the LH group were significantly lower than those of the control group, whereas those of the non-LH rats were not significantly different from those of the control and LH rats.

CONCLUSIONS

These results suggest that LH rats but not non-LH rats experienced down-regulations of claudin-5 and AQP-4 in the CA-1 and CA-3. It is possible that a region-specific modulation of claudin-5 and AQP-4 is involved in the mechanisms of vulnerability but not resilience in depression.

摘要

背景

尽管动物和临床研究的结果表明血脑屏障(BBB)有助于各种精神疾病(包括抑郁症)的发病机制,但潜在的机制尚不清楚。我们研究了习得性无助(LH)大鼠(抑郁症动物模型)和非 LH 大鼠(韧性模型)星形胶质细胞中紧密连接蛋白 claudin-5 和水通道蛋白 4(AQP-4)的水平。

方法

我们对大鼠进行不可避免的轻度电击,然后通过电击后测试来鉴定 LH 和非 LH 大鼠。然后通过 Western blot 分析评估 LH 和非 LH 大鼠几个脑区的 claudin-5 和 AQP-4 表达。

结果

LH 组 CA-1 和 CA-3 海马区的 claudin-5 和 AQP-4 水平明显低于对照组,而非 LH 组则与对照组和 LH 组无明显差异。

结论

这些结果表明,LH 大鼠而非非 LH 大鼠经历了 CA-1 和 CA-3 中 claudin-5 和 AQP-4 的下调。Claudin-5 和 AQP-4 的区域特异性调节可能参与了抑郁症易感性而不是韧性的机制。

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