We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Reducing histone acetylation rescues cognitive deficits in a mouse model of Fragile X syndrome.
- Authors
Yue Li; Stockton, Michael E.; Eisinger, Brian E.; Yinghua Zhao; Miller, Jessica L.; Bhuiyan, Ismat; Yu Gao; Zhiping Wu; Junmin Peng; Xinyu Zhao
- Abstract
Fragile X syndrome (FXS) is the most prevalent inherited intellectual disability, resulting from a loss of fragile X mental retardation protein (FMRP). Patients with FXS suffer lifelong cognitive disabilities, but the function of FMRP in the adult brain and the mechanism underlying age-related cognitive decline in FXS is not fully understood. Here, we report that a loss of FMRP results in increased protein synthesis of histone acetyltransferase EP300 and ubiquitination-mediated degradation of histone deacetylase HDAC1 in adult hippocampal neural stem cells (NSCs). Consequently, FMRP-deficient NSCs exhibit elevated histone acetylation and age-related NSC depletion, leading to cognitive impairment in mature adult mice. Reducing histone acetylation rescues both neurogenesis and cognitive deficits in mature adult FMRP-deficient mice. Our work reveals a role for FMRP and histone acetylation in cognition and presents a potential novel therapeutic strategy for treating adult FXS patients.
- Subjects
FRAGILE X syndrome; HISTONE acetylation; ACETYLATION; DEACETYLATION; NEURAL stem cells; HISTONE acetyltransferase; COGNITION disorders; HISTONES
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-04869-3