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Research Paper|Volume 12, Issue 3|pp 2471—2484

Sepsis induced cognitive impairments by disrupting hippocampal parvalbumin interneuron-mediated inhibitory network via a D4-receptor mechanism

Muhuo Ji1, Shuming Li2, Ling Zhang2, Yuzhu Gao3, Qiuting Zeng2, Minjie Mao2, Jianjun Yang1
  • 1Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Nanjing, China
  • 2Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
  • 3Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
Received: October 10, 2019Accepted: January 7, 2020Published: February 4, 2020
https://doi.org/10.18632/aging.102755

Copyright: © 2020 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.