Cerebellar Apoptotic Parameters and Circulating MiRNAs in Senile UChB Rats (Voluntary Ethanol Consumers)

Author(s): Martinez M, Rossetto I. M. U, Lizarte F. S. N, Tirapelli L. F, Tirapelli D. P. C, Fioravante V. C, Chuffa L. G. A, Martinez F. E.

Despite the lack of scientific data on the real impact of alcohol consumption in the elderly, excessive drinking is relatively common in this population. Aging is accompanied by reduced water content, diminished hepatic metabolic capacity, and altered brain responsiveness, making older individuals more vulnerable to alcohol-induced neurotoxicity. The cerebellum is particularly sensitive to ethanol, with documented impairments in motor coordination, balance, and cognitive functions. However, the effects of chronic ethanol exposure during senescence remain poorly understood. This study investigated apoptotic and anti-apoptotic signaling in the aged cerebellum of UChB rats, a strain characterized by voluntary ethanol consumption, and evaluated the expression of circulating microRNAs associated with apoptotic pathways. Immunohistochemistry and gene expression analyses revealed no
significant changes in cerebellar caspase-3, XIAP, or IGFR1 expression between ethanol-consuming and control aged rats, although minor differences in protein immunolocalization were observed. Conversely, serum levels of miR-9-3p, miR-15b-5p, miR-16-5p, miR-21, miR-200a, and miR-222-3p were significantly upregulated in the ethanol group. Taken together, the findings suggest that senile UChB rats develop a tolerance to chronic ethanol intake, preventing further activation of apoptotic cascades in the cerebellum. Additionally, the modulation of specific circulating miRNAs indicates a potential regulatory or compensatory role in this adaptive response. These miRNAs may serve as molecular indicators of ethanol exposure in aging and contribute to understanding mechanisms of neurobiological tolerance.