Neuroscience 2005 Abstract
| Presentation Number: | 115.15 |
|---|---|
| Abstract Title: | Acute stress induces sex-specific changes in serum corticosterone in fragile X knock-out mice. |
| Authors: |
Markham, J. A.*1,2
; Estrada, C. M.3
; Greenough, W. T.1,2,4
1Beckman Inst., Univ. of Illinois, Urbana, IL 2Psychology, Univ. of Illinois, Urbana, IL 3Molecular & Integrative Physiol, Univ. of Illinois, Urbana, IL 4Neuroscience Program, Univ. of Illinois, Urbana, IL |
| Primary Theme and Topics |
Disorders of the Nervous System - Developmental Disorders -- Genetic |
| Session: |
115. Down's and Fragile X Syndromes Poster |
| Presentation Time: | Saturday, November 12, 2005 3:00 PM-4:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # WW13 |
| Keywords: | FMRP, HPA AXIS, GLUCOCORTICOID, SEX DIFFERENCES |
Fragile X Syndrome (FXS) is the most common form of inherited mental retardation and results from the silencing of the Fmr1 gene that encodes the Fragile X Mental Retardation Protein (FMRP). FMRP binds the mRNA for the glucocorticoid receptor, expression of which is reduced in apical dendrites of CA1 pyramidal neurons (Neuron 37:417-31). The hippocampus is involved in the negative feedback loop regulating the stress response, and the response to acute stress is elevated in children with FXS (PNEC 27:855-72;J Dev Behav Pediatr 21:278-82). Here we confirm our preliminary finding that Fmr1 null mice have a prolonged elevation of serum glucocorticoid in response to an acute stressor (SFN’03, #646.5) and report that the stress response of the KO mouse varies according to sex.
Male and female (40-45 days) Fmr1 KO and WT control mice (N13C57Bl/6) were exposed to 30 min. of acute restraint stress. Serum corticosterone levels were assayed from unstressed animals and those examined either immediately following stress or after a 15 or 60 minute recovery period. There were no baseline differences in serum corticosterone levels between genotypes, however females had higher baseline levels than males.
Additionally, there was a significant sex*genotype*treatment interaction (p<.01). Similar to FXS patients, serum glucocorticoid levels of male KO mice exhibited a protracted return to baseline following acute stress, relative to WT males. Both KO and WT females’ serum corticosterone levels were still elevated relative to baseline after 60 minutes of recovery from acute stress, however, levels for WT females were reduced at this time relative to peak levels (evident after 15 minutes of recovery), whereas KO females’ levels were continuing to climb at this latest time point examined. These data suggest that the hypothalamic-pituitary-adrenal axis is misregulated in Fragile X KO mice as in FXS patients, and that the profile of feedback misregulation is sex-dependent.
Male and female (40-45 days) Fmr1 KO and WT control mice (N13C57Bl/6) were exposed to 30 min. of acute restraint stress. Serum corticosterone levels were assayed from unstressed animals and those examined either immediately following stress or after a 15 or 60 minute recovery period. There were no baseline differences in serum corticosterone levels between genotypes, however females had higher baseline levels than males.
Additionally, there was a significant sex*genotype*treatment interaction (p<.01). Similar to FXS patients, serum glucocorticoid levels of male KO mice exhibited a protracted return to baseline following acute stress, relative to WT males. Both KO and WT females’ serum corticosterone levels were still elevated relative to baseline after 60 minutes of recovery from acute stress, however, levels for WT females were reduced at this time relative to peak levels (evident after 15 minutes of recovery), whereas KO females’ levels were continuing to climb at this latest time point examined. These data suggest that the hypothalamic-pituitary-adrenal axis is misregulated in Fragile X KO mice as in FXS patients, and that the profile of feedback misregulation is sex-dependent.
Supported by FRAXA, NIMH
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
Copyright © 2005-2026 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
