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