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

• Published in: Psychoneuroendocrinology 2006-07, Vol.31 (6), p.781-785
• Main Authors: Markham, Julie A., Beckel-Mitchener, Andrea C., Estrada, Christina M., Greenough, William T.
• Format: Article
• Language: English
• Subjects: Acute restraint; Adaptation, Physiological; Analysis of Variance; Animals; Behavioral psychophysiology; Biological and medical sciences; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Corticosterone - blood; Disease Models, Animal; Feedback, Physiological; Female; Fmr1; FMRP; Fragile X Mental Retardation Protein - genetics; Fragile X Mental Retardation Protein - metabolism; Fragile X Syndrome - blood; Fundamental and applied biological sciences. Psychology; Glucocorticoid; Hormones and behavior; Male; Medical genetics; Medical sciences; Mice; Mice, Knockout; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptors, Glucocorticoid - metabolism; Restraint, Physical; RNA, Messenger - analysis; Sex difference; Sex Factors; Stress, Psychological - blood
• ISSN: 0306-4530; 1873-3360
• DOI: 10.1016/j.psyneuen.2006.02.008

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).