Age-related memory deficits are associated with changes in protein degradation in brain regions critical for trace fear conditioning.

Autor: Dulka BN; Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA., Pullins SE; Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA., Cullen PK; Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA., Moyer JR Jr; Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA., Helmstetter FJ; Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA. Electronic address: fjh@uwm.edu.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2020 Jul; Vol. 91, pp. 160-166. Date of Electronic Publication: 2020 Mar 07.
DOI: 10.1016/j.neurobiolaging.2020.03.001
Abstrakt: Brain aging is accompanied by an accumulation of damaged proteins, which results from deterioration of cellular quality control mechanisms and decreased protein degradation. The ubiquitin-proteasome system (UPS) is the primary proteolytic mechanism responsible for targeted degradation. Recent work has established a critical role of the UPS in memory and synaptic plasticity, but the role of the UPS in age-related cognitive decline remains poorly understood. Here, we measured markers of UPS function and related them to fear memory in rats. Our results show that age-related memory deficits are associated with reductions in phosphorylation of the Rpt6 proteasome regulatory subunit and corresponding increases in lysine-48 (K48)-linked ubiquitin tagging within the basolateral amygdala. Increases in K48 polyubiquitination were also observed in the medial prefrontal cortex and dorsal hippocampus. These data suggest that protein degradation is a critical component of age-related memory deficits. This extends our understanding of the relationship between the UPS, aging, and memory, which is an important step toward the prevention and treatment of deficits associated with normal cognitive aging and memory-related neurodegenerative diseases.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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