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bioRxiv · 10.1101/2020.01.12.903112

Modeling human age-associated increase in Gadd45γ expression leads to spatial recognition memory impairments in young adult mice

Brito, D. V.·Gulmez Karaca, K.·Kupke, J.·Mudlaff, F.·Zeuch, B.·Gomes, R.·Lopes, L. V.·Oliveira, A. M. M.
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Abstract

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 (Gadd45{gamma}) during aging and cognition. We report that Gadd45{gamma} expression is increased in the hippocampus of aged humans and that Gadd45{gamma} overexpression in the young adult mouse hippocampus compromises cognition. Moreover, Gadd45{gamma} overexpression in hippocampal neurons disrupted CREB signaling and the expression of well-established activity-regulated genes. This work shows that Gadd45{gamma} expression is tightly controlled in the hippocampus and its disruption may be a mechanism contributing to age-related cognitive impairments observed in humans.

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Brito, D. V., Gulmez Karaca, K., Kupke, J., Mudlaff, F., Zeuch, B., Gomes, R., Lopes, L. V., Oliveira, A. M. M.. 2020-01-14. Modeling human age-associated increase in Gadd45γ expression leads to spatial recognition memory impairments in young adult mice. https://doi.org/10.1101/2020.01.12.903112

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