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

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

doi:10.1016/j.psyneuen.2006.02.008

« Previous Next »Psychoneuroendocrinology
Volume 31, Issue 6 , Pages 781-785, July 2006

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

Julie A. Markham
- Beckman Institute, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana, IL 61801, USA
- Department of Psychology, University of Illinois at Urbana-Champaign, 603 East Daniel Street, Champaign, IL 61820, USA
- Corresponding author. Address: Beckman Institute, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana, IL 61801, USA. Tel.: +1 217 333 3753; fax: +1 217 244 5180.
Andrea C. Beckel-Mitchener
- Molecular, Cellular, and Genomic Neuroscience Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, Neuroscience Center, 6001 Executive Boulevard, Bethesda, MD 20892-9641, USA
- This work was not written as part of Andrea Beckel-Mitchener's official duties as a Government employee. The views expressed in this article do not necessarily represent the views of the NIMH, NIH, HHS, or the United States Government.
Christina M. Estrada
- Department of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, 393 Morrill Hall, 505 South Goodwin Avenue, Urbana, IL 61801, USA
William T. Greenough
- Beckman Institute, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana, IL 61801, USA
- Department of Psychology, University of Illinois at Urbana-Champaign, 603 East Daniel Street, Champaign, IL 61820, USA
- Department of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, 393 Morrill Hall, 505 South Goodwin Avenue, Urbana, IL 61801, USA
- Neuroscience Program, University of Illinois at Urbana-Champaign, 318B Morrill Hall, 505 South Goodwin Avenue, Urbana, IL 61801, USA

Received 10 October 2005; received in revised form 23 January 2006; accepted 20 February 2006.

Summary

Fragile X syndrome (FXS), the most common form of inherited mental retardation, results from the silencing of the Fmr1 gene that encodes the Fragile X mental retardation protein (FMRP). Because (1) mRNA for the glucocorticoid receptor is bound by FMRP and (2) the response to acute stress is elevated in children with FXS, we examined whether this heightened response is characteristic of a mouse model of FXS. Fmr1 knockout (KO) and wildtype (WT) control mice were exposed to 30min of acute restraint; serum corticosterone levels were assayed from unstressed animals and those examined either immediately following stress or after a 15 or 60min recovery period. Under unstressed conditions, KOs and WTs did not differ in serum corticosterone, although both genotype and sex affected corticosterone levels observed following exposure to acute stress. Similar to FXS patients, serum glucocorticoid levels of KO mice exhibited a protracted return to baseline following acute stress. This suggests that the stress response is misregulated in Fmr1 KO mice as in FXS patients and provides the first evidence for a link between a particular FMRP-binding mRNA and a functional phenotype of FXS (impaired glucocorticoid negative feedback).