Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reports in the clinical literature and studies of fmr1 knockout mice have led to the hypothesis that, in addition to mental retardation, fragile X syndrome is characterized by a dysregulation of hypothalamic-pituitary-adrenal axis function. We have systematically examined this hypothesis by studying the effects of stress on adrenocorticotrophic hormone and corticosterone levels in adult, male fmr1 knockout mice. Initially we determined the circadian rhythms of the plasma hormone levels in both wild-type and fmr1 knockout mice and established the optimal time to impose the stress. We found no genotypic differences in the circadian rhythms of either hormone. We studied two types of stressors, immobilization and spatial novelty; spatial novelty was 5min in an elevated plus-maze. We varied the duration of immobilization and followed the time course of recovery of hormones to their pre-stress levels. Despite the lower anxiety exhibited by fmr1 knockout mice in the elevated plus-maze, hormonal responses to and recovery from this spatial novelty were similar in both genotypes. Further, we found no genotypic differences in hormonal responses to immobilization stress. The results of our study indicate that, in FVB/NJ mice, the hormonal response to and recovery from acute stress is unaltered by the lack of fragile X mental retardation protein.
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PMID:Unaltered hormonal response to stress in a mouse model of fragile X syndrome. 1847 37

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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PMID:Enhanced corticosteroid signaling alters synaptic plasticity in the dentate gyrus in mice lacking the fragile X mental retardation protein. 2573 48