Proteome-wide analysis of the hippocampus in adolescent male mice with learning and memory impairment caused by chronic ethanol exposure

Alcohol consumption may cause various impairments in the brain. The hippocampus is particularly vulnerable to alcohol exposure, which may cause learning and memory deficits. Recently, proteomics analysis has become a popular approach to explore the pathogenesis of various diseases. The present study was conducted to investigate protein expression alteration in the hippocampus and to identify the molecular mechanisms underlying ethanol-induced learning and memory impairments. Mouse models of chronic ethanol intoxication were established by intragastrical administration for 28 consecutive days, and hippocampal neuronal damage was assessed by Nissl staining. Recognition memory was evaluated by Novel object recognition and Morris water maze tests, and hippocampus tissues were collected for label-free quantitative proteomics and analyzed using bioinformatics methods. Our study showed that chronic ethanol exposure prompted marked changes in protein expression in the hippocampus. We identified 32 differentially expressed proteins, of which 21 were upregulated and 11 downregulated. Gene Ontology analysis suggested that the identified differentially proteins were mainly involved in cytoskeleton and signal transduction mechanisms. Further verification using Western blotting and real-time quantitative PCR revealed that the hippocampal CTSL (cathepsin L), and PVALB (Parvalbumin) showed strongest expression changes, the latter being specifically expressed in GABAergic interneurons. These two proteins might serve as candidate protein biomarkers, providing new prospects for the diagnosis and treatment of ethanol-induced learning and memory disorders.