PT  - JOURNAL ARTICLE
AU  - David V.C. Brito
AU  - Kubra Gulmez Karaca
AU  - Janina Kupke
AU  - Franziska Mudlaff
AU  - Benjamin Zeuch
AU  - Rui Gomes
AU  - Luísa V. Lopes
AU  - Ana M.M. Oliveira
TI  - Modeling human age-associated increase in Gadd45γ expression leads to spatial recognition memory impairments in young adult mice
AID  - 10.1101/2020.01.12.903112
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.12.903112
4099  - http://biorxiv.org/content/early/2020/01/14/2020.01.12.903112.short
4100  - http://biorxiv.org/content/early/2020/01/14/2020.01.12.903112.full
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.