Chronic Intermittent Ethanol Exposure Alters Behavioral Flexibility in Aged Rats Compared to Adult Rats and Modifies Protein and Protein Pathways Related to Alzheimer's Disease

Repeated excessive alcohol consumption increases the risk of developing cognitive decline and dementia. Hazardous drinking among older adults further increases such vulnerabilities. To investigate whether alcohol induces cognitive deficits in older adults, we performed a chronic intermittent ethanol exposure paradigm (ethanol or water gavage every other day 10 times) in 8 week-old young adult and 70-week-old aged rats. While spatial memory retrieval ascertained by probe trials in the Morris water maze was not significantly different between ethanol-treated and water-treated rats in both age groups after the fifth and tenth gavages, behavioral flexibility was impaired in ethanol-treated rats compared to water-treated rats in the aged group but not in the young adult group. We then examined ethanol-treatment-associated hippocampal proteomic and phosphoproteomic differences distinct in the aged rats. We identified several ethanol-treatment-related proteins, including the upregulations of the Prkcd protein level, several of its phosphosites, and its kinase activity and downregulation in the Camk2a protein level. Our bioinformatic analysis revealed notable changes in pathways involved in neurotransmission regulation, synaptic plasticity, neuronal apoptosis, and insulin receptor signaling. In conclusion, our behavioral and proteomic results identified several candidate proteins and pathways potentially associated with alcohol-induced cognitive decline in aged adults.

Automated summary

Repeated excessive alcohol consumption increases the risk of cognitive decline and dementia in older adults. This study found that chronic intermittent ethanol exposure impaired behavioral flexibility in aged rats but not in young adult rats. Proteomic analysis revealed alcohol treatment-related changes in proteins and pathways associated with neural transmission, synaptic plasticity, neuronal apoptosis, and insulin receptor signaling. These findings contribute to understanding the detrimental effects of alcohol on cognitive function in older adults.