Depression is highly comorbid with anxiety disorders and associated with profound cognitive impairment. Moreover, cognitive deficits associated with hippocampal dysfunction are central in depression and anxiety disorders. Furthermore, depression is accompanied by glutamatergic dysfunction which can further impair the functioning of the hippocampus. Recent studies have shown that N-acetyl cysteine (NAC), a glutamate modulator produces an antidepressant-like effect by normalization of the periterminal release of glutamate and/or antioxidant effects. However, the effects of repeated NAC treatment on depression-induced anxiety, cognitive deficits, and associated neurochemical and structural alterations are relatively unknown. Accordingly, we investigated whether chronic NAC treatment could reverse cognitive deficits, and associated hippocampal volume loss and monoaminergic alterations in the neonatal clomipramine (CLI) model of depression. We found that chronic NAC treatment produces antidepressive and antianhedonic-like effects. NAC treatment also reversed CLI-induced anxiety. Interestingly, repeated NAC treatment improved the performance of CLI rats in rewarded alternation task in T-maze. The antidepressive-like and procognitive effects of NAC was associated with normalization of volume loss in CA1, dentate gyrus (DG) and hilar subfields of the hippocampus. Furthermore, NAC restored CLI-induced decrease in levels of monoamines and normalized enhanced metabolism in the hippocampus. Taken together, chronic NAC treatment ameliorates depressive and anxiety-like behavior, spatial learning deficits, and reverses CLI-induced pathological alterations at structural and neurochemical levels in the hippocampus. Our findings might help in evolving NAC as a viable pharmacotherapy for reversal of cognitive deficits in depression and associated disorders.

中文翻译：

---

N-乙酰基半胱氨酸可通过恢复海马亚区的体积和相关的神经化学变化来缓解抑郁症引起的认知功能障碍。

抑郁症与焦虑症高度合并，并伴有严重的认知障碍。此外，与海马功能障碍相关的认知缺陷是抑郁症和焦虑症的中心。此外，抑郁症伴有谷氨酸能功能障碍，其可进一步损害海马的功能。最近的研究表明，谷氨酸调节剂N-乙酰半胱氨酸（NAC）通过使谷氨酸的周围末端释放正常化和/或抗氧化作用来产生抗抑郁样作用。但是，反复进行NAC治疗对抑郁症引起的焦虑，认知缺陷以及相关的神经化学和结构改变的影响相对未知。因此，我们调查了慢性NAC治疗是否可以逆转认知缺陷，以及新生儿抑郁症的氯米帕明（CLI）模型中相关的海马体积减少和单胺能改变。我们发现，慢性NAC治疗会产生抗抑郁和类似antanhedonic的作用。NAC治疗还可以逆转CLI引起的焦虑症。有趣的是，反复的NAC处理提高了CLI大鼠在T型迷宫中有奖交替任务中的表现。NAC的抗抑郁样和认知作用与海马CA1区，齿状回（DG）和肺门亚区体积损失的正常化有关。此外，NAC恢复了CLI诱导的海马中单胺水平的下降和正常化的新陈代谢增强。总而言之，慢性NAC治疗可改善抑郁和焦虑样行为，空间学习障碍，并逆转了CLI诱导的海马结构和神经化学水平的病理改变。我们的发现可能有助于发展NAC作为逆转抑郁症和相关疾病认知缺陷的可行药物疗法。