title: Stress and vitamin D: altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats.
abstract: Exposure to stressful life events is associated with the onset of major depression and increases the risk of cardiac morbidity and mortality. While recent evidence has indicated the existence of an interrelationship between local vitamin D (VD) metabolism and many aspects of human physiology including brain and heart function, much is still unknown concerning the biological link between VD signaling and stress-induced depressive behavior and cardiac dysfunction. In the present study, we observed the VD intracrine system in the hippocampus and myocardium of chronic unpredictable mild stress (CUMS) exposed rats. After 4 weeks of CUMS procedure, rats were induced to a depressive-like state and the cytochromes P450 enzymes involved in VD activating and catabolizing (CYP27B1 and CYP24A1 respectively) and VD receptor (VDR) were assessed by real time RT-PCR and western blot in the hippocampus, myocardium and kidney. In the hippocampus of depressed rats, CYP27B1, CYP24A1 and VDR expression were significantly increased and the local status of 1,25-dihydroxyvitamin D (1,25(OH)2D) was higher compared with controls. Furthermore, hippocampal mRNA levels of VD target genes (calbindin-d28k, neurotrophin-3) and RXRα (heterodimeric partner of VDR) were upregulated in response to chronic stress. Similar to the hippocampus, CUMS also induced CYP27B1/CYP24A1/VDR expression in the myocardium. However, renal metabolism of VD and serum1,25(OH)2D status were unchanged. Meanwhile, sertraline treatment could partly normalize the stress-induced alterations of VD metabolism. In conclusion, this study firstly showed a co-elevated expression of CYP27B1/CYP24A1/VDR in both the hippocampus and myocardium of CUMS rats, which suggests VD signaling may be involved in the compensatory mechanism that protect from stress-induced deteriorating effects on the brain and heart.
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha, China; School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Jiang
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Zhang
authors.forename: Huan-De
authors.initials: HD
authors.lastname: Li
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Cai
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Liu
authors.forename: Lin-Yao
authors.initials: LY
authors.lastname: Chen
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002908:Chronic Disease; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; C585551:Cyp24a1 protein, rat; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
keywords: Chronic unpredictable mild stress; Depression; Hippocampus; Myocardium; Sertraline; Vitamin D