RT Journal Article
SR Electronic
T1 Modeling human age-associated increase in Gadd45γ expression leads to spatial recognition memory impairments in young adult mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.12.903112
DO 10.1101/2020.01.12.903112
A1 David V.C. Brito
A1 Kubra Gulmez Karaca
A1 Janina Kupke
A1 Franziska Mudlaff
A1 Benjamin Zeuch
A1 Rui Gomes
A1 Luísa V. Lopes
A1 Ana M.M. Oliveira
YR 2020
UL http://biorxiv.org/content/early/2020/06/29/2020.01.12.903112.abstract
AB 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 CREB 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.Competing Interest StatementThe authors have declared no competing interest.