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

Psychoneuroendocrinology
Julie A MarkhamW T Greenough

Abstract

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 30 min of acute restraint; serum corticosterone levels were assayed from unstressed animals and those examined either immediately following stress or after a 15 or 60 min 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).

References

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Citations

Sep 7, 2011·Developmental Neuroscience·Jose Luis Olmos-Serrano, Joshua G Corbin
Sep 7, 2011·Developmental Neuroscience·Dejan B Budimirovic, Walter E Kaufmann
Sep 13, 2007·Molecular Psychiatry·S S Moy, J J Nadler
May 11, 2011·Current Opinion in Neurobiology·Aparna Suvrathan, Sumantra Chattarji
Nov 5, 2008·Journal of the American Academy of Child and Adolescent Psychiatry·Cindy C HaganAllan L Reiss
Apr 9, 2011·Journal of Neurodevelopmental Disorders·Lisa CordeiroDavid Hessl
Jun 26, 2007·Trends in Neurosciences·Charlotte D'Hulst, R Frank Kooy
Aug 2, 2008·Journal of Intellectual Disability Research : JIDR·L Hulbert-Williams, R P Hastings
May 16, 2008·Psychoneuroendocrinology·Mei Qin, Carolyn Beebe Smith
Jan 19, 2013·Behavioural Brain Research·D OddiS Pietropaolo
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·T L RadzyukevichJ A Heiny
Jan 23, 2018·Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology·Stefanny Christie Monteiro TitonFernando Ribeiro Gomes
Jun 12, 2020·Frontiers in Behavioral Neuroscience·Jamshid Faraji, Gerlinde A S Metz
Dec 30, 2020·Journal of Psychiatric Research·Jennifer L BrunoAllan L Reiss

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