Corticosterone response to acute stress in a mouse model of Fragile X syndrome

Markham, Julie A.; Beckel-Mitchener, Andrea; Estrada, Christina M.; Greenough, William T.

doi:10.1016/j.psyneuen.2006.02.008

Cited by 47 publications

(38 citation statements)

References 14 publications

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“…Our results differ from reports in the literature in which fmr1 KO mice were similarly stressed (Lauterborn, 2004;Markham et al, 2006). Baseline levels of CORT in our mice tended to be lower and effects of restraint greater than those reported in either study.…”

Section: Measurementscontrasting

confidence: 99%

“…Serum corticosterone (CORT) levels were elevated after either 30 min or 2 h of immobilization in both genotypes, but effects were greater in KOs after 2 h of stress. Following immobilization stress, serum CORT concentrations recovered more slowly in KO mice (Markham et al, 2006). In addition, one of the mRNAs bound by FMRP is a glucocorticoid receptor mRNA (Miyashiro et al 2003).…”

Section: Introductionmentioning

confidence: 94%

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Unaltered hormonal response to stress in a mouse model of fragile X syndrome

Qin

Smith

2008

Psychoneuroendocrinology

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SummaryReports in the clinical literature and studies of fmr-1 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 5 min 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 fmr-1 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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Section: Measurementscontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Unaltered hormonal response to stress in a mouse model of fragile X syndrome

Qin

Smith

2008

Psychoneuroendocrinology

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“…For example, Restivo and colleagues 59 found that exposure to an enriched environment can not only reverse some behavioral deficits in the Fmr1-null mouse, but can also fully rescue aberrant dendritic morphology in the FXS model. On the other hand, alterations in function of the hypothalamic-pituitary-adrenal axis, as observed in Fmr1-null mice 334 (see also Ref. 335) and in the mouse model of Rett syndrome, 82,83 suggest that some mutant lines may have abnormal sensitivity to stressful environmental conditions, which could be reflected in measures of anxiety-like responses, activity, social approach and interaction, and other types of behavior.…”

Section: Discussionmentioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

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Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism.

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“…Fragile X individuals (Hessl et al, 2002;Hessl et al, 2006), as well as Fmr1 KO mice (Markham et al, 2006), have also been shown to have an exaggerated stress response.…”

Section: Discussionmentioning

confidence: 99%

“…Both fragile X patients and Fmr1 KO mice have a delayed return to baseline glucocorticoid levels, which was explained by the normal binding of GR mRNA to FMRP (Miyashiro et al, 2003). Fragile X individuals and Fmr1 KO mice do not express FMRP, thus in the absence of FMRP inappropriate transport or translation of GR could lead to altered HPA responsiveness (Markham et al, 2006). Mice with CGG-repeats shorter than 170 trinucleotides have close to normal Fmrp levels (figure 1).…”

Section: Discussionmentioning

confidence: 99%

Altered hypothalamus–pituitary–adrenal gland axis regulation in the expanded CGG-repeat mouse model for fragile X-associated tremor/ataxia syndrome

Brouwer

Severijnen

Jong

et al. 2008

Psychoneuroendocrinology

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The human FMR1 gene contains an unstable CGG-repeat in its 5′ untranslated region. The repeat length in the normal population is polymorphic (5-54 CGG-repeats). Individuals carrying lengths beyond 200 CGGs (i.e. the full mutation) show hypermethylation and as a consequence gene silencing of the FMR1 gene. The absence of the gene product FMRP causes the fragile X syndrome, the most common inherited form of mental retardation. Elderly carriers of the premutation (PM), which is defined as a repeat length between 55-200 CGGs, can develop a progressive neurodegenerative syndrome: fragile X-associated tremor/ataxia syndrome (FXTAS). The high FMR1 mRNA levels observed in cells from PM carriers have led to the hypothesis that FXTAS is caused by a pathogenic RNA gain-of-function mechanism. Apart from tremor/ataxia, specific psychiatric symptoms have been described in PM carriers with or without FXTAS. Since these symptoms could arise from elevated stress hormone levels, we investigated hypothalamicpituitary-adrenal (HPA) axis regulation using a knock-in mouse model with an expanded CGGrepeat in the PM range (>98 repeats) in the Fmr1 gene, which shows repeat instability, and displays biochemical, phenotypic and neuropathological characteristics of FXTAS. We show elevated levels of corticosterone in serum and ubiquitin-positive inclusions in both the pituitary and adrenal gland of 100-week old animals. In addition, we demonstrate ubiquitin-positive © 2008 Elsevier Ltd. All rights reserved. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Financial disclosuresWe declare no conflict of interest. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript inclusions in the amygdala from aged expanded CGG-repeat mice. We hypothesize that altered regulation of the HPA axis and the amygdala and higher stress hormone levels in the mouse model for FXTAS may explain associated psychological symptoms in humans.

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Corticosterone response to acute stress in a mouse model of Fragile X syndrome

Cited by 47 publications

References 14 publications

Unaltered hormonal response to stress in a mouse model of fragile X syndrome

Unaltered hormonal response to stress in a mouse model of fragile X syndrome

Advances in behavioral genetics: mouse models of autism

Altered hypothalamus–pituitary–adrenal gland axis regulation in the expanded CGG-repeat mouse model for fragile X-associated tremor/ataxia syndrome

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