Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Nanjing, China.
Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
Aging (Albany NY). 2020 Feb 4;12(3):2471-2484. doi: 10.18632/aging.102755.
Patients who suffer sepsis often develop cognitive impairments, yet the underlying mechanisms largely remain to be elucidated. Increasing evidence has suggested that parvalbumin (PV) interneurons are required for the synchronization of neural activities and higher brain processes, whereas its dysfunction is implicated in many psychiatric disorders. In the present study, we examined the role of hippocampal PV interneuron-mediated inhibitory network in a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP) and also explored the underlying mechanism. Here we showed that CLP-induced cognitive impairments, which were accompanied by significantly decreased expressions of PV and dopamine 4 (D4) receptor, decreased slow γ oscillation band, and reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs). Notably, D4 receptor agonist RO-10-5824 treatment was able to reverse most of these abnormities. In summary, our study suggests that sepsis might disrupt PV interneuron-mediated network function that is dependent on the D4 receptor, leading to abnormal γ oscillation and consequent cognitive impairments.
患有败血症的患者常出现认知障碍，但潜在的机制在很大程度上仍未阐明。越来越多的证据表明，钙结合蛋白（PV）中间神经元对于神经活动和高级脑过程的同步至关重要，而其功能障碍与许多精神疾病有关。在本研究中，我们研究了在盲肠结扎和穿孔（CLP）诱导的多微生物败血症大鼠模型中，海马 PV 中间神经元介导的抑制性网络的作用，并探讨了其潜在机制。我们发现，CLP 诱导的认知障碍与 PV 和多巴胺 4（D4）受体的表达显著降低、慢 γ 振荡带减少以及抑制性突触后电流（mIPSCs）频率降低有关。值得注意的是，D4 受体激动剂 RO-10-5824 治疗能够逆转这些异常的大部分。综上所述，我们的研究表明，败血症可能会破坏依赖 D4 受体的 PV 中间神经元介导的网络功能，导致异常的 γ 振荡和随后的认知障碍。
