Inborn differences in environmental reactivity predict divergent diurnal behavioral, endocrine, and gene expression rhythms

PSYCHONEUROENDOCRINOLOGY

卷:37

Article

Kerman, Ilan A.^1,2  Clinton, Sarah M.^1,2  Simpson, Danielle N.¹  Bedrosian, Tracy A.³  Bernard, Rene⁴  Akil, Huda²  Watson, Stanley J.² 

[1] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA

[2] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA

[3] Ohio State Univ, Grad Program Neurosci, Columbus, OH 43210 USA

[4] Charite Hosp, Inst Integrat Neuroanat, Berlin, Germany

关键词: Bred high responder;    Bred low responder;    Circadian;    Clock;    Per1;    Per2;    AVP;    CRH;    Glucocorticoid receptor;    Mineralocorticoid receptor;    Corticosterone;   

DOI  :  10.1016/j.psyneuen.2011.06.010

来源: Elsevier

【 摘 要 】

Circadian dysfunction has long been implicated in the etiology of mood disorders. The gene Clock and related molecules (e.g. Per1, Per2) represent key regulators of circadian rhythmicity, and their targeted disruption in mutant mice produces potentiated reward drive, novelty-seeking, impulsivity, disrupted sleep, reduced depression and anxiety - a behavioral profile highly reminiscent of our selectively bred high responder (bHR) rats compared to bred low responders (bLRs). The current study evaluated potential diurnal bHR-bLR differences in behavior, gene expression, and neuroendocrinology. Relative to bHRs, bLRs showed diminished homecage locomotion during the dark (but not light) phase and a delayed corticosterone peak. In situ hybridizations in hypothalamus, amygdala, and hippocampus at Zeitgeber Time (ZT)2 and ZT14 revealed distinct bHR-bLR-day night gene expression fluctuations. bHRs exhibited altered day-night patterns of corticotrophin releasing hormone (CRH) and arginine vasopression (AVP) mRNA in the hypothalamus, and perturbed hippocampal MR:GR ratios relative to bLR rats. bHR-bLR rats showed disparate day-night Clock expression in the suprachiasmatic nucleus, a master circadian oscillator, with bHRs showing higher levels at ZT14 versus ZT2 and bLRs showing the opposite pattern. Clock, Pen1 and Per2 were assessed in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) since disruption of these genes induces bHR-like behavior in mutant mice. Clock and Pen1 did not differ between strains, but there were robust Per2 differences, with bHRs having reduced Per2 in VTA and SNc. These findings resonate with earlier work demonstrating that perturbation of Clock and related molecules contributes to disturbances of emotional and addictive behaviors. (C) 2011 Published by Elsevier Ltd.

【 授权许可】

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