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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Depression following traumatic brain injury in mice is associated with down-regulation of hippocampal astrocyte glutamate transporters by thrombin
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Depression following traumatic brain injury in mice is associated with down-regulation of hippocampal astrocyte glutamate transporters by thrombin

机译：小鼠创伤性脑损伤后的抑郁与凝血酶的海马星形胶质细胞谷氨酸转运蛋白的下调有关

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摘要

Depression after traumatic brain injury (TBI) is common but the mechanisms by which TBI causes depression are unknown. TBI decreases glutamate transporters GLT-1 and GLAST and allows extravasation of thrombin. We examined the effects of thrombin on transporter expression in primary hippocampal astrocytes. Application of a PAR-1 agonist caused down-regulation of GLT-1, which was prevented by inhibition of Rho kinase (ROCK). To confirm these mechanisms in vivo, we subjected mice to closed-skull TBI. Thrombin activity in the hippocampus increased one day following TBI. Seven days following TBI, expression of GLT-1 and GLAST was reduced in the hippocampus, and this was prevented by administration of the PAR-1 antagonist SCH79797. Inhibition of ROCK attenuated the decrease in GLT-1, but not GLAST, after TBI. We measured changes in glutamate levels in the hippocampus seven days after TBI using an implanted biosensor. Stress-induced glutamate levels were significantly increased following TBI and this was attenuated by treatment with the ROCK inhibitor fasudil. We quantified depressive behavior following TBI and found that inhibition of PAR-1 or ROCK decreased these behaviors. These results identify a novel mechanism by which TBI results in down-regulation of astrocyte glutamate transporters and implicate astrocyte and glutamate transporter dysfunction in depression following TBI.
机译：创伤性脑损伤（TBI）抑郁症是常见的，但TBI导致抑郁症的机制是未知的。 TBI降低谷氨酸转运蛋白GLT-1和凝血酶渗透并允许外渗。我们检查了凝血酶对原发性海马星形胶质细胞转运蛋白表达的影响。 PAR-1激动剂的应用导致GLT-1的调节，通过抑制Rho激酶（岩石）来防止。为了确认体内体内机制，我们将小鼠与闭合颅骨TBI进行。在TBI之后，海马中的凝血酶活性增加了一天。 TBI后七天，在海马中降低了GLT-1和PLAST的表达，通过施用PAR-1拮抗剂SCH79797预防这一点。抑制岩石减弱了TBI之后的GLT-1的减少，但不会粘滞。我们使用植入的生物传感器在TBI七天七天测量了海马谷氨酸水平的变化。在TBI后，应激诱导的谷氨酸水平显着增加，并且通过用岩石抑制剂Fasudil治疗衰减。我们在TBI后量化抑郁行为，发现抑制PAR-1或岩石降低了这些行为。这些结果鉴定了一种新的机制，使得TBI导致星形胶质细胞谷氨酸转运蛋白的下调，并暗示TBI后抑郁症和谷氨酸转运蛋白功能障碍。

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