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Alcohol ; 107: 108-118, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36155778

RESUMEN

Chronic alcohol consumption, Alzheimer's disease (AD), and vascular dementia are all associated with cognitive decline later in life, raising questions about whether their underlying neuropathology may share some common features. Indeed, recent evidence suggests that ethanol exposure during adolescence or intermittent drinking in young adulthood increased neuropathological markers of AD, including both tau phosphorylation and beta-amyloid (Aß) accumulation. The goal of the present study was to determine whether alcohol consumption later in life, a time when microglia and other neuroimmune processes tend to become overactive, would influence microglial clearance of Aß(1-42), focusing specifically on microglia in close proximity to the neurovasculature. To do this, male and female Fischer 344 rats were exposed to a combination of voluntary and involuntary ethanol consumption from ∼10 months of age through ∼14 months of age. Immunofluorescence revealed profound sex differences in microglial co-localization, with Aß(1-42) showing that aged female rats with a history of ethanol consumption had a higher number of iba1+ cells and marginally reduced expression of Aß(1-42), suggesting greater phagocytic activity of Aß(1-42) among females after chronic ethanol consumption later in life. Interestingly, these effects were most prominent in Iba1+ cells near neurovasculature that was stained with tomato lectin. In contrast, no significant effects of ethanol consumption were observed on any markers in males. These findings are among the first reports of a sex-specific increase in microglia-mediated phagocytosis of Aß(1-42) by perivascular microglia in aged, ethanol-consuming rats, and may have important implications for understanding mechanisms of cognitive decline associated with chronic drinking.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Disfunción Cognitiva , Etanol , Microglía , Animales , Femenino , Masculino , Ratas , Factores de Edad , Consumo de Bebidas Alcohólicas/efectos adversos , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides/metabolismo , Enfermedad Crónica , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Etanol/toxicidad , Ratones Transgénicos , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/fisiología , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiología , Factores Sexuales
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