Modeling human age-associated increase in Gadd45γ expression leads to spatial recognition memory impairments in young adult mice.
Adult
Aged
Aging
/ genetics
Animals
Cognition
/ physiology
Cognitive Aging
/ psychology
Cyclic AMP Response Element-Binding Protein
/ metabolism
Disease Models, Animal
Female
Gene Expression
Gene Expression Regulation
/ genetics
Hippocampus
/ metabolism
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Male
Memory Disorders
/ genetics
Middle Aged
Spatial Memory
/ physiology
Young Adult
GADD45 Proteins
Activity-regulated gene expression
Age-related cognitive deficits
CREB
Gadd45γ
Object location memory
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
12
01
2020
revised:
22
05
2020
accepted:
27
06
2020
pubmed:
28
7
2020
medline:
30
6
2021
entrez:
26
7
2020
Statut:
ppublish
Résumé
Aging is associated with the progressive decay of cognitive function. Hippocampus-dependent processes, such as the formation of spatial memory, are particularly vulnerable to aging. Currently, the molecular mechanisms responsible for age-dependent cognitive decline are largely unknown. Here, we investigated the expression and function of the growth arrest DNA damage gamma (Gadd45γ) during aging and cognition. We report that Gadd45γ expression is increased in the hippocampus of aged humans and that Gadd45γ overexpression in the young adult mouse hippocampus compromises cognition. Moreover, Gadd45γ overexpression in hippocampal neurons disrupted cAMP response element-binding protein signaling and the expression of well-established activity-regulated genes. This work shows that Gadd45γ expression is tightly controlled in the hippocampus and its disruption may be a mechanism contributing to age-related cognitive impairments observed in humans.
Identifiants
pubmed: 32711258
pii: S0197-4580(20)30214-1
doi: 10.1016/j.neurobiolaging.2020.06.021
pii:
doi:
Substances chimiques
Cyclic AMP Response Element-Binding Protein
0
Intracellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
281-286Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.