TY - JOUR
T1 - 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
AU - Ho, Ada Man Choi
AU - Peyton, Mina P.
AU - Scaletty, Samantha J.
AU - Trapp, Sarah
AU - Schreiber, Areonna
AU - Madden, Benjamin J.
AU - Choi, Doo Sup
AU - Matthews, Douglas B.
N1 - Funding Information:
This study was funded by Mayo Clinic ─ UWEC Research Innovation Council. This study was partially supported by the Samuel C. Johnson Genomics of Addiction Program at the Mayo Clinic, the Ulm Foundation, the National Institute on Alcohol Abuse and Alcoholism (AA028968 and AA029258), and the National Institute on Aging (AG072898).
Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/12/20
Y1 - 2022/12/20
N2 - 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.
AB - 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.
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U2 - 10.1021/acsomega.2c04528
DO - 10.1021/acsomega.2c04528
M3 - Article
AN - SCOPUS:85143870217
SN - 2470-1343
VL - 7
SP - 46260
EP - 46276
JO - ACS Omega
JF - ACS Omega
IS - 50
ER -