Systemic inflammation induces cognitive impairments via unclear mechanisms. Accumulating evidence has demonstrated that a subset of neurons that express parvalbumin (PV) play a critical role in regulation of cognitive and emotional behavior. Thus, the aim of the present study was to test whether disruption of PV interneuron mediates systemic inflammation-induced depression-like behavior and working memory impairment by lipopolysaccharide (LPS) challenge. Here we showed that LPS induces depression-like behavior and working memory impairment, coinciding with increased PV expression, enhanced GABAergic transmission, and impaired long-term potentiation (LTP) in the hippocampus. Notably, systemic administration of NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was able to interfere with PV expression and reverse depression-like behavior and working memory impairment, which is probably mediated by reversing impaired LTP. In addition, flumazenil, a competitive antagonist acting at the benzodiazepine binding site of the GABAA receptor, also ameliorated these abnormal behaviors. Collectively, our study added growing evidence to the limited studies that overinhibition mediated by PV interneurons might play a critical role in LPS-induced depression-like behavior and working memory impairment.

中文翻译：

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小白蛋白中间神经元介导的过度抑制可能导致脂多糖激发引起的抑郁样行为和工作记忆障碍。

全身性炎症通过不清楚的机制引起认知障碍。越来越多的证据表明，表达小白蛋白（PV）的神经元子集在调节认知和情绪行为中起关键作用。因此，本研究的目的是测试PV中间神经元的破坏是否通过脂多糖（LPS）激发介导系统性炎症诱导的抑郁样行为和工作记忆损害。在这里，我们发现LPS诱发抑郁样行为和工作记忆障碍，与PV表达增加，GABA能传递增强和海马的长期增强（LTP）受损相吻合。值得注意的是 NMDA（N-甲基-D-天冬氨酸）受体（NMDAR）拮抗剂氯胺酮的全身性给药能够干扰PV表达并逆转抑郁样行为和工作记忆障碍，这可能是由逆转LTP受损引起的。此外，作用于GABAA受体的苯二氮卓结合位点的竞争性拮抗剂氟马西尼也改善了这些异常行为。总的来说，我们的研究为有限的研究增加了越来越多的证据，即PV中间神经元介导的过度抑制可能在LPS诱发的抑郁样行为和工作记忆障碍中起关键作用。也改善了这些异常行为。总的来说，我们的研究为有限的研究增加了越来越多的证据，即PV中间神经元介导的过度抑制可能在LPS诱发的抑郁样行为和工作记忆障碍中起关键作用。也改善了这些异常行为。总的来说，我们的研究为有限的研究增加了越来越多的证据，即PV中间神经元介导的过度抑制可能在LPS诱发的抑郁样行为和工作记忆障碍中起关键作用。