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

Neurobiology of Disease
M GhilanBrian R Christie

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.

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Citations

Jun 28, 2016·Neuroscience and Biobehavioral Reviews·Crystal BostromBrian R Christie
May 1, 2012·Trends in Neurosciences·Rhiannon M MeredithIoannis Kramvis
Mar 31, 2018·Frontiers in Molecular Neuroscience·Regina Dahlhaus
Jun 19, 2017·Neuroscience and Biobehavioral Reviews·Cristina PinarBrian R Christie

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