Proteomics

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Chronic intermittent ethanol exposure selectively impairs behavioral flexibility in aged rats compared to adult rats and modifies protein and protein pathways related to Alzheimer's disease


ABSTRACT: Repeated excessive alcohol consumption increases the risk of developing cognitive decline and dementia. Hazardous drinking among older adults further increases such vulnerabilities. In order to understand the molecular mechanisms underlying alcohol-induced 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 than water-treated rats in the aged group but not in the young adult group. Further proteomic and phosphoproteomic analyses on their hippocampal tissues by tandem mass tag mass spectrometry revealed ethanol-treatment-associated proteomic and phosphoproteomic differences distinct to the aged rats, including the upregulations of Prkcd protein level, several of its phosphosites, and its kinase activity and the same aspects in Camk2a but downregulated, and were enriched in pathways involved in neurotransmission regulation, synaptic plasticity, neuronal apoptosis, and insulin receptor signaling. In conclusion, our behavioral and proteomic results added several candidate proteins and pathways potentially associated with alcohol-induced cognitive decline in aged adults.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Benjamin Madden  

LAB HEAD: Ada Ho

PROVIDER: PXD034443 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications

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.

Ho Ada Man-Choi AM   Peyton Mina P MP   Scaletty Samantha J SJ   Trapp Sarah S   Schreiber Areonna A   Madden Benjamin J BJ   Choi Doo-Sup DS   Matthews Douglas B DB  

ACS omega 20221207 50


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 wate  ...[more]

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