Faculty Collaboration Database

Age-related memory deficits are associated with changes in protein degradation in brain regions critical for trace fear conditioning. Neurobiol Aging 2020 Jul;91:160-166

Date

04/14/2020

Pubmed ID

32280031

Pubmed Central ID

PMC7232789

DOI

10.1016/j.neurobiolaging.2020.03.001

Scopus ID

2-s2.0-85083015866 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

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.

Author List

Dulka BN, Pullins SE, Cullen PK, Moyer JR Jr, Helmstetter FJ

Author

Fred Helmstetter PhD Professor in the Psychology / Neuroscience department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Amygdala
Animals
Cognitive Aging
Conditioning, Classical
Fear
Hippocampus
Male
Memory
Memory Disorders
Phosphorylation
Prefrontal Cortex
Proteasome Endopeptidase Complex
Proteolysis
Rats, Inbred F344
Ubiquitin