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童年期创伤是引发与压力有关的精神病的最重要风险因素之一,例如创伤后压力障碍或抑郁.尽管已证实星形胶质细胞在调节递质释放和突触可塑性中发挥作用,然而目前尚不清楚星形胶质递质代谢在这种应激诱导的精神病理学中所起的作用.在啮齿动物,可以通过青少年应激暴露来模拟童年逆境,从而导致焦虑加剧以及成年后应对压力的能力下降.我们描述了这种幼年应激大鼠,无论成年期是否有其他应激,都会导致腹侧CA1(vCA1)Schaffer侧支的突触效力降低,而高频刺激后突触传递的长时程增强(LTP)增加.我们通过阻断星形胶质谷氨酸降解酶谷氨酰胺合成酶(GS)测试谷氨酸-谷氨酰胺循环是否引起青少年应激后可塑性的持久变化.用蛋氨酸亚砜亚胺对正常大鼠的切片中GS的药理抑制的确模仿青少年应激对vCA1-LTP的影响,而提供谷氨酰胺足以使LTP正常化.评估在青少年、成年期或青少年/成年联合应激后, vCA1辐射层中的稳态mRNA水平揭示了GS、星形细胞谷氨酸和谷氨酰胺转运蛋白表达的明显变化.尽管青少年应激后GS mRNA表达水平持续降低,但GS蛋白水平保持稳定.本研究结果表明,星形胶质细胞和谷氨酸-谷氨酰胺循环在介导青少年应激对vCA1(与焦虑和情绪记忆处理有关的区域)的可塑性的长期影响中起关键作用.“,”A traumatic childhood is among the most important risk factors for developing stress-related psycho-pathologies such as posttraumatic stress disorder or depression later in life. However, despite the proven role of astrocytes in regulating transmitter release and synaptic plasticity, the contribution of astrocytic transmitter metab-olism to such stress-induced psychopathologies is currently not understood. In rodents, childhood adversity can be modeled by juvenile stress exposure, resulting in increased anxiety, and impaired coping with stress in adult-hood. We describe that such juvenile stress in rats, regardless of additional stress in adulthood, leads to reduced synaptic efficacy in the ventral CA1 (vCA1) Schaffer collaterals, but increased long-term potentiation (LTP) of synaptic transmission after high-frequency stimulation. We tested whether the glutamate-glutamine-cycle guides the lasting changes on plasticity observed after juvenile stress by blocking the astrocytic glutamate-degrading en-zyme, glutamine synthetase (GS). Indeed, the pharmacological inhibition of GS by methionine sulfoximine in slices from na?ve rats mimics the effect of juvenile stress on vCA1-LTP, while supplying glutamine is sufficient to normalize the LTP. Assessing steady-state mRNA levels in the vCA1 stratum radiatum reveals distinct shifts in the expression of GS, astrocytic glutamate, and glutamine transporters after stress in juvenility, adulthood, or com-bined juvenile/adult stress. While GS mRNA expression levels are lastingly reduced after juvenile stress, GS pro-tein levels are maintained stable. Together our results suggest a critical role for astrocytes and the glutamate-gluta-mine cycle in mediating long-term effects of juvenile stress on plasticity in the vCA1, a region associated with anxiety and emotional memory processing.