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  • Alcohol-drinking during later life by C57BL/6J mice induces sex- and age-dependent changes in hippocampal and prefrontal cortex expression of glutamate receptors and neuropathology markers.

Alcohol-drinking during later life by C57BL/6J mice induces sex- and age-dependent changes in hippocampal and prefrontal cortex expression of glutamate receptors and neuropathology markers.

Addiction neuroscience (2023-07-03)
Karen K Szumlinski, Jessica N Herbert, Brenda Mejia Espinoza, Lauren E Madory, Samantha L Scudder
ABSTRACT

Heavy drinking can induce early-onset dementia and increase the likelihood of the progression and severity of Alzheimer's Disease and related dementias (ADRD). Recently, we showed that alcohol-drinking by mature adult C57BL/6J mice induces more signs of cognitive impairment in females versus males without worsening age-related cognitive decline in aged mice. Here, we immunoblotted for glutamate receptors and protein markers of ADRD-related neuropathology within the hippocampus and prefrontal cortex (PFC) of these mice after three weeks of alcohol withdrawal to determine protein correlates of alcohol-induced cognitive decline. Irrespective of alcohol history, age-related changes in protein expression included a male-specific decline in hippocampal glutamate receptors and an increase in the expression of a beta-site amyloid precursor protein cleaving enzyme (BACE) isoform in the PFC as well as a sex-independent increase in hippocampal amyloid precursor protein. Alcohol-drinking was associated with altered expression of glutamate receptors in the hippocampus in a sex-dependent manner, while all glutamate receptor proteins exhibited significant alcohol-related increases in the PFC of both sexes. Expression of BACE isoforms and phosphorylated tau varied in the PFC and hippocampus based on age, sex, and drinking history. The results of this study indicate that withdrawal from a history of alcohol-drinking during later life induces sex- and age-selective effects on glutamate receptor expression and protein markers of ADRD-related neuropathology within the hippocampus and PFC of potential relevance to the etiology, treatment and prevention of alcohol-induced dementia and Alzheimer's Disease.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-TAU antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-APP Antibody, Upstate®, from rabbit
Sigma-Aldrich
Anti-BACE Antibody, CT, clone 61-3E7, clone 61-3E7, Chemicon®, from mouse
Sigma-Aldrich
Anti-Glutamate receptor 1 Antibody, from rabbit, purified by affinity chromatography
Sigma-Aldrich
Anti-CaM Kinase II Antibody, α subunit, clone 6G9, clone 6G9, Upstate®, from mouse
Sigma-Aldrich
Anti-Metabotropic Glutamate Receptor 5 Antibody, pain, Chemicon®, from rabbit