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Neurobiol Dis. 2015 May;77:26-34. doi: 10.1016/j.nbd.2015.01.008. Epub 2015 Feb 27.

Enhanced corticosteroid signaling alters synaptic plasticity in the dentate gyrus in mice lacking the fragile X mental retardation protein.

Author information

1
Graduate Program in Neuroscience, University of Victoria, Victoria, BC, Canada; Department of Biology, University of Victoria, Victoria, BC, Canada; Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
2
Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
3
Graduate Program in Neuroscience, University of Victoria, Victoria, BC, Canada; Department of Biology, University of Victoria, Victoria, BC, Canada; Division of Medical Sciences, University of Victoria, Victoria, BC, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada. Electronic address: brain64@uvic.ca.

Abstract

The fragile X mental retardation protein (FMRP) is an important regulator of protein translation, and a lack of FMRP expression leads to a cognitive disorder known as fragile X syndrome (FXS). Clinical symptoms characterizing FXS include learning impairments and heightened anxiety in response to stressful situations. Here, we report that, in response to acute stress, mice lacking FMRP show a faster elevation of corticosterone and a more immediate impairment in N-methyl-d-aspartate receptor (NMDAR) dependent long-term potentiation (LTP) in the dentate gyrus (DG). These stress-induced LTP impairments were rescued by administering the glucocorticoid receptor (GR) antagonist RU38486. Administration of RU38486 also enhanced LTP in Fmr1(-/y) mice in the absence of acute stress to wild-type levels, and this enhancement was blocked by application of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid. These results suggest that a loss of FMPR results in enhanced GR signaling that may adversely affect NMDAR dependent synaptic plasticity in the DG.

KEYWORDS:

Dentate gyrus; FMRP; Fmr1; Fragile X; Hippocampus; LTP; NMDA; Stress; Synaptic plasticity

PMID:
25731748
DOI:
10.1016/j.nbd.2015.01.008
[Indexed for MEDLINE]
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