Neonatal maternal separation (NMS), as an early-life stress (ELS), is a risk factor to develop emotional disorders. However, the exact mechanisms remain to be defined. In the present study, we investigated the mechanisms involved in developing emotional disorders caused by NMS. First, we confirmed that NMS provoked impulsive behavior, orienting and nonselective attention-deficit, abnormal grooming, and depressive-like behaviors in adolescence. Excitatory amino acid carrier 1 (EAAC1) is an excitatory amino acid transporter expressed specifically by neurons and is the route for the neuronal uptake of glutamate/aspartate/cysteine. Compared with that in the normal control group, EAAC1 expression was remarkably reduced in the ventral hippocampus and cerebral cortex in the NMS group. Additionally, EAAC1 expression was reduced in parvalbumin-positive hippocampal GABAergic neurons in the NMS group. We also found that EAAC1-knockout (EAAC1−/−) mice exhibited impulsive-like, nonselective attention-deficit, and depressive-like behaviors compared with WT mice in adolescence, characteristics similar to those of the NMS behavior phenotype. Taken together, our results revealed that ELS induced a reduction in EAAC1 expression, suggesting that reduced EAAC1 expression is involved in the pathophysiology of attention-deficit and depressive behaviors in adolescence caused by NMS.

新生儿母亲分离（NMS）作为一种早期生活压力（ELS），是发生情绪障碍的危险因素。然而，确切的机制仍有待确定。在本研究中，我们研究了 NMS 引起的情绪障碍的机制。首先，我们证实 NMS 会引发青春期的冲动行为、定向性和非选择性注意力缺陷、异常梳理行为和抑郁样行为。兴奋性氨基酸载体 1 (EAAC1) 是神经元特异性表达的兴奋性氨基酸转运蛋白，是神经元摄取谷氨酸/天冬氨酸/半胱氨酸的途径。与正常对照组相比，NMS组腹侧海马和大脑皮层EAAC1表达显着降低。此外，NMS 组小白蛋白阳性海马 GABA 能神经元中 EAAC1 表达降低。我们还发现，与WT小鼠相比，EAAC1敲除（EAAC1−/−）小鼠在青春期表现出冲动样、非选择性注意力缺陷和抑郁样行为，这些特征与NMS行为表型相似。综上所述，我们的结果表明，ELS 诱导 EAAC1 表达减少，表明 EAAC1 表达减少与 NMS 引起的青春期注意力缺陷和抑郁行为的病理生理学有关。