Neuroinflammation plays a key role in the progression of many neurodegenerative diseases, yet the underlying mechanism remains largely unexplored. Using an animal model of neuroinflammation induced by repeated lipopolysaccharide (LPS) injections, we found selectively reduced expression of parvalbumin (PV) but not somatostatin (SST) in the medial prefrontal cortex (mPFC). The reduced PV expression resulted in decreased intensities of vesicular GABA transporter and PV buttons, suggesting disinhibition in the mPFC. These further induced abnormal mPFC neural activities and consequently contributed to cognitive impairments. In addition, gamma oscillations supported by PV interneuron function were positively associated with time spent with the novel object in the novel object recognition test. Notably, down-regulation of neuroinflammation by microglia inhibitor minocycline or boosting gamma oscillations by dopamine 4 receptor agonist RO-10-5824 improved cognitive performance. In conclusion, our study proposes neural network disturbance as a likely mechanistic linker between neuroinflammation and cognitive impairments in neurodegeneration and possibly other psychiatric disorders.

中文翻译：

---

内侧前额叶皮层的神经网络障碍可能导致神经炎症引起的认知障碍

神经炎症在许多神经退行性疾病的进展中起着关键作用，但其潜在机制在很大程度上仍未得到探索。使用重复脂多糖 (LPS) 注射诱导的神经炎症动物模型，我们发现内侧前额叶皮层 (mPFC) 中小清蛋白 (PV) 而非生长抑素 (SST) 的表达选择性降低。PV 表达的减少导致囊泡 GABA 转运蛋白和 PV 按钮的强度降低，表明 mPFC 的去抑制作用。这些进一步诱导了异常的 mPFC 神经活动，从而导致认知障碍。此外，PV 中间神经元功能支持的伽马振荡与在新物体识别测试中与新物体花费的时间呈正相关。尤其，通过小胶质细胞抑制剂米诺环素下调神经炎症或通过多巴胺 4 受体激动剂 RO-10-5824 增强伽马振荡改善认知能力。总之，我们的研究提出神经网络障碍可能是神经炎症与神经退行性疾病和可能的其他精神疾病中的认知障碍之间的机械连接器。