Stress and vitamin D: Altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats
Stress and vitamin D: Altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats
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DOI：
10.1016/j.psyneuen.2013.03.017
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发表时间：
2013-10-01
影响因子：
3.7
通讯作者：
Chen, Lin-Yao
中科院分区：
文献类型：
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作者：
Jiang, Pei;Zhang, Wen-Yuan;Chen, Lin-Yao
暴露在应激性生活事件中与严重抑郁症的发病有关，并增加了心脏发病率和死亡率的风险。虽然最近的证据表明局部维生素D(VD)代谢与包括大脑和心脏功能在内的人类生理的许多方面存在相互关系，但关于VD信号与应激诱导的抑郁行为和心功能障碍之间的生物学联系仍不清楚。在本研究中，我们观察了慢性不可预测轻度应激(CUMS)暴露大鼠的海马区和心肌区VD的内分泌系统。造模4周后，诱导大鼠进入类抑郁状态，用实时定量RT-PCR和免疫印迹法检测大鼠海马、心肌和肾脏中参与VD激活和分解代谢的细胞色素P450酶(分别为CYP27B1和CYP24A1)和VD受体(VDR)的表达。在抑郁大鼠的海马区，细胞色素P27B1、细胞色素P24A1和维生素D受体的表达显著增加，1，25-二羟基维生素D(1，25(OH)(2)D)的局部状态高于对照组。此外，慢性应激还上调了VD靶基因(Calbindin-d28k、NN-营养素-3)和RXRα(VDR的异二聚体伙伴)的mRNA水平。与海马区相似，CUMS也可诱导心肌细胞中细胞色素P27B1/细胞色素24A1/维生素D受体的表达。但VD患者肾脏代谢及血清1，25(OH)(2)D状态无明显变化。同时，舍曲林治疗可部分恢复应激所致的VD代谢改变。综上所述，本研究首次在CUMS大鼠的海马区和心肌中发现了细胞色素P27B1/细胞色素P24A1/维生素D受体的共同表达，提示VD信号可能参与了保护脑组织和心脏免受应激损伤的代偿机制。(C)2013爱思唯尔有限公司。保留所有权利。
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)(2)D) was higher compared with controls. Furthermore, hippocampal mRNA levels of VD target genes (calbindin-d28k, neurotrophin-3) and RXR alpha (hetero-dimeric 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)(2)D 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. (C) 2013 Elsevier Ltd. All rights reserved.