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Title: Effects of voluntary exercise on cell proliferation and neurogenesis in the dentate gyrus of adult FMR1 knockout mice
Authors: Pinar, C
Yau, SY 
Sharp, Z
Shamer, A
Fontaine, CJ
Meconi, AL
Lottenberg, CP
Christie, BR
Issue Date: 2018
Source: Brain plasticity, 2018, v. 4, no. 2, p. 185-195
Abstract: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability that can be traced to a single gene mutation. This disorder is caused by the hypermethylation of the Fmr1 gene, which impairs translation of Fragile X Mental Retardation Protein (FMRP). In Fmr1 knockout (KO) mice, the loss of FMRP has been shown to negatively impact adult hippocampal neurogenesis, and to contribute to learning, memory, and emotional deficits. Conversely, physical exercise has been shown to enhance cognitive performance, emotional state, and increase adult hippocampal neurogenesis. In the current experiments, we used two different voluntary running paradigms to examine how exercise impacts adult neurogenesis in the dorsal and ventral hippocampal dentate gyrus (DG) of Fmr1 KO mice. Immunohistochemical analyses showed that short-term (7 day) voluntary running enhanced cell proliferation in both wild-type (WT) and Fmr1 KO mice. In contrast, long-term (28 day) running only enhanced cell proliferation in the whole DG of WT mice, but not in Fmr1 KO mice. Interestingly, cell survival was enhanced in both WT and Fmr1 KO mice following exercise. Interestingly we found that running promoted cell proliferation and survival in the ventral DG of WTs, but promoted cell survival in the dorsal DG of Fmr1 KOs. Our data indicate that long-term exercise has differential effects on adult neurogenesis in ventral and dorsal hippocampi in Fmr1 KO mice. These results suggest that physical training can enhance hippocampal neurogenesis in the absence of FMRP, may be a potential intervention to enhance learning and memory and emotional regulation in FXS.
Keywords: Fragile-x syndrome
Publisher: IOS Press
Journal: Brain plasticity 
ISSN: 2213-6304
EISSN: 2213-6312
DOI: 10.3233/BPL-170052
Rights: © 2018 – IOS Press and the authors. All rights reserved
This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0).
The following publication Pinar, C., Yau, S. Y., Sharp, Z., Shamei, A., Fontaine, C. J., Meconi, A. L., ... & Christie, B. R. (2018). Effects of voluntary exercise on cell proliferation and neurogenesis in the dentate gyrus of adult FMR1 knockout mice. Brain Plasticity, 4(2), 185-195 is available at
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