Department of Neurobiology, Interdisciplinary Centre for Neurosciences (IZN), Heidelberg University, Heidelberg, Germany.
Department of Neurobiology, Interdisciplinary Centre for Neurosciences (IZN), Heidelberg University, Heidelberg, Germany; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Neurobiol Aging. 2020 Oct;94:281-286. doi: 10.1016/j.neurobiolaging.2020.06.021. Epub 2020 Jul 3.
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.
衰老是认知功能逐渐衰退的原因。海马依赖的过程，如空间记忆的形成，特别容易受到衰老的影响。目前，导致与年龄相关的认知能力下降的分子机制在很大程度上尚不清楚。在这里，我们研究了生长停滞 DNA 损伤γ（Gadd45γ）在衰老和认知过程中的表达和功能。我们报告说，Gadd45γ 在衰老人类的海马体中的表达增加，并且在年轻成年小鼠海马体中的 Gadd45γ 过表达会损害认知能力。此外，海马神经元中的 Gadd45γ 过表达会破坏 cAMP 反应元件结合蛋白信号和既定的活性调节基因的表达。这项工作表明，Gadd45γ 的表达在海马体中受到严格控制，其破坏可能是导致人类观察到的与年龄相关的认知障碍的一种机制。
