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
- 1 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Nanjing, China
- 2 Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
- 3 Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
Received: October 10, 2019 Accepted: January 7, 2020 Published: February 4, 2020https://doi.org/10.18632/aging.102755
How to Cite
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.