Research Paper Volume 12, Issue 22 pp 23146—23164
pSynGAP1 disturbance-mediated hippocampal oscillation network impairment might contribute to long-term neurobehavioral abnormities in sepsis survivors
- 1 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Received: January 8, 2020 Accepted: August 17, 2020 Published: November 16, 2020https://doi.org/10.18632/aging.104080
How to Cite
Copyright: © 2020 Wang 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.
Although more patients survive sepsis and are increasingly discharged from the hospital, they often experience long-term cognitive and psychological impairment with significant socioeconomic impact. However, the pathophysiological mechanisms have not been fully elucidated. In the present study, we showed that LPS induced long-term neurobehavioral abnormities, as reflected by significantly decreased freezing time to context and sucrose preference. Using a high-throughput quantitative proteomic screen, we showed that phosphorylation of synaptic GTPase-activating protein 1 (pSynGAP1) was identified as the hub of synaptic plasticity and was significantly decreased following LPS exposure. This decreased pSynGAP was associated with significantly lower theta and gamma oscillations in the CA1 of the hippocampus. Notably, restoration of pSynGAP1 by roscovitine was able to reverse most of these abnormities. Taken together, our study suggested that pSynGAP1 disturbance-mediated hippocampal oscillation network impairment might play a critical role in long-term neurobehavioral abnormities of sepsis survivors.