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.