Language

English

Publication Date

12-1-2025

Journal

eLife

DOI

10.7554/eLife.106273

PMID

41324576

PMCID

PMC12668675

PubMedCentral® Posted Date

12-1-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Age-related neurodegenerative diseases involve reduced cell numbers and impaired behavioral capacity. Neurodegeneration and behavioral deficits also occur during aging, and notably in the absence of disease. The cerebellum, which modulates movement and cognition, is susceptible to cell loss in both aging and disease. Here, we demonstrate that cerebellar Purkinje cell loss in aged mice is not spatially random but rather occurs in a pattern of parasagittal stripes. We also find that aged mice exhibit impaired motor coordination and more severe tremor compared to younger mice. However, the relationship between patterned Purkinje cell loss and motor dysfunction is not straightforward. Examination of postmortem samples of human cerebella from neurologically typical individuals supports the presence of selective loss of Purkinje cells during aging. These data reveal a spatiotemporal cellular substrate for aging in the cerebellum that may inform how neuronal vulnerability leads to neurodegeneration and the ensuing deterioration of behavior.

Keywords

Animals, Purkinje Cells, Aging, Mice, Humans, Cerebellum, Mice, Inbred C57BL, Male, Female

Published Open-Access

yes

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