Journal
HIPPOCAMPUS
Volume 22, Issue 6, Pages 1220-1224Publisher
WILEY-BLACKWELL
DOI: 10.1002/hipo.20989
Keywords
Fragile X Syndrome; Fmr1; neurogenesis; learning and memory; cognition
Categories
Funding
- National Institutes of Health [DC5793]
- NIH/NIA [AG033570]
- Brain Research Foundation
- FRAXA Research Foundation
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Fragile X syndrome (FXS) is the most common form of inherited intellectual disability in humans. Individuals affected with the disorder exhibit a deficiency of the fragile X mental retardation protein (FMRP), due to transcriptional silencing of the Fmr1 gene. It is widely accepted that learning deficits in FXS result from impaired synaptic function and/or plasticity in the brain. Interestingly, recent evidence suggests that conditional knockout of Fmr1 in neural progenitor cells in mice impairs hippocampal neurogenesis, which in turn contributes to learning impairments. To examine the nature of the neurogenic impairments and determine whether they impact the morphology of the dentate gyrus, we assessed the extent of neural progenitor cell proliferation, survival, and differentiation in older adult Fmr1 knockout mice. Here, we show that the number of fast-proliferating cells in the subgranular layer of the dentate gyrus, as well as the subsequent survival of these cells, are dramatically reduced in Fmr1 knockout mice. In addition, the number of mature neurons in the granule layer of the dentate gyrus of these mice is significantly smaller than in wild type littermate controls, suggesting that impaired proliferation and survival of neural progenitor cells compromises the structure of the dentate gyrus. Impaired adult neurogenesis may underlie, at least in part, the learning deficits that characterize fragile X syndrome. (c) 2011 Wiley Periodicals, Inc.
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