Faculty Collaboration Database

Integrated Excitatory/Inhibitory Imbalance and Transcriptomic Analysis Reveals the Association between Dysregulated Synaptic Genes and Anesthetic-Induced Cognitive Dysfunction. Cells 2022 Aug 11;11(16)

Date

08/27/2022

Pubmed ID

36010580

Pubmed Central ID

PMC9406780

DOI

10.3390/cells11162497

Scopus ID

2-s2.0-85136592621 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

Emerging evidence from human epidemiologic and animal studies has demonstrated that developmental anesthesia neurotoxicity could cause long-term cognitive deficits and behavioral problems. However, the underlying mechanisms remain largely unknown. We conducted an electrophysiological analysis of synapse activity and a transcriptomic assay of 24,881 mRNA expression on hippocampal tissues from postnatal day 60 (P60) mice receiving propofol exposure at postnatal day 7 (P7). We found that developmentally propofol-exposed P60 mouse hippocampal neurons displayed an E/I imbalance, compared with control mice as evidenced by the decreased excitation and increased inhibition. We found that propofol exposure at P7 led to the abnormal expression of 317 mRNAs in the hippocampus of P60 mice, including 23 synapse-related genes. Various bioinformatic analyses revealed that these abnormally expressed synaptic genes were associated with the function and development of synapse activity and plasticity, E/I balance, behavior, and cognitive impairment. Our findings suggest that the altered E/I balance may constitute a mechanism for propofol-induced long-term impaired learning and memory in mice. The transcriptomic and bioinformatic analysis of these dysregulated genes related to synaptic function paves the way for development of therapeutic strategies against anesthetic neurodegeneration through the restoration of E/I balance and the modification of synaptic gene expression.

Author List

Yan Y, Logan S, Liu X, Chen B, Jiang C, Arzua T, Ramchandran R, Liu QS, Bai X

Authors

Xiaowen Bai PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anesthetics
Animals
Cognitive Dysfunction
Hippocampus
Humans
Mice
Propofol
Transcriptome