ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Mimicking Age-Associated Gadd45γ Dysregulation Results in Memory Impairments in Young Adult Mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Article
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- Dnmt3a1 regulates hippocampus-dependent memory via the downstream target Nrp1.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- VEGFD signaling balances stability and activity-dependent structural plasticity of dendrites.Cellular and molecular life sciences : CMLS · 2024Article
- Biphasic Npas4 expression promotes inhibitory plasticity and suppression of fear memory consolidation in mice.Molecular psychiatry · 2024Article
- Assessing cognitive decline in the aging brain: lessons from rodent and human studies.npj aging · 2023Review
- Sex-specific and opposed effects of FKBP51 in glutamatergic and GABAergic neurons: Implications for stress susceptibility and resilience.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Single-cell transcriptomic atlas of mouse cochlear aging.Protein & cell · 2023Article
- Roles for GADD45 in Development and Cancer.Advances in experimental medicine and biology · 2022Review
- Regulation of neuronal plasticity by the DNA repair associated Gadd45 proteins.Current research in neurobiology · 2022Review
- Gadd45 in Neuronal Development, Function, and Injury.Advances in experimental medicine and biology · 2022Review
- MeCP2 gates spatial learning-induced alternative splicing events in the mouse hippocampus.Molecular brain · 2020Article
- DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer.Signal transduction and targeted therapy · 2020Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Age-related memory loss is observed across multiple mammalian species and preferentially affects hippocampus-dependent memory. Memory impairments are characterized by accelerated decay of spatial memories. Nevertheless, the molecular mechanisms underlying these deficits are still largely unknown. Here, we investigated the expression and function of the growth arrest DNA damage (Gadd45) family during aging and cognition, respectively. We report that aging impairs the expression of Gadd45γ in the hippocampus of cognitively impaired male mice. Mimicking this decrease in young adult male mice led to age-like memory deficits in hippocampus-dependent memory tasks. Gadd45γ reduction impaired the activity of key components of the mitogen-activated protein kinase (MAPK) pathway (p38 and JNK) in mouse hippocampal cultures. Furthermore, we found that activation of downstream targets, such as ATF-2, c-Jun, and CREB (cAMP response element-binding protein), was disrupted. Finally, we showed that Gadd45γ is required for induction of key early- and late-response genes that have been associated with aging. Together, these findings indicate that Gadd45γ expression regulates cognitive abilities and synapse-to-nucleus communication and suggest Gadd45γ dysfunction as a potential mechanism contributing to age-related cognitive impairments.
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