Neurochemical effects of chronic administration of calcitriol in rats.
Neurochemical effects of chronic administration of calcitriol in rats.
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作者：
Jiang P;Zhang LH;Cai HL;Li HD;Liu YP;Tang MM;Dang RL;Zhu WY;Xue Y;He X
尽管越来越多的数据显示了维生素D(VD)的各种神经作用，但它对大脑神经化学的影响仍然远未完全被了解。为了进一步研究VD对神经化学的影响，我们评估了给予骨化三醇(1，25-二羟基维生素D)(50 ng/kg/天或100 ng/kg/天)6周后大鼠大脑中的神经递质系统。两种剂量的骨化三醇均可提高VDR蛋白水平，但不影响血钙和血磷水平。接受骨化三醇治疗的大鼠，尤其是大剂量的骨化三醇，表现出γ-氨基丁酸(GABA)状态的升高。相应地，谷氨酸脱羧酶(GAD)67的mRNA表达增加。100 ng/kg骨化三醇也可增加前额叶皮质谷氨酸和谷氨酰胺水平，但不改变谷氨酰胺合成酶(GS)的表达。此外，骨化三醇治疗促进酪氨酸羟化酶(TH)和色氨酸羟化酶2(TPH2)的表达，而不改变多巴胺和5-羟色胺的状态。而多巴胺和5-羟色胺代谢产物浓度升高，单胺氧化酶A(MAOA)表达明显增加，这可能与维持多巴胺和5-羟色胺能神经传递的动态平衡有关。总而言之，本研究首次展示了骨化三醇对主要神经递质系统的影响，为VD在脑功能中的作用提供了新的证据。
Despite accumulating data showing the various neurological actions of vitamin D (VD), its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D) administration (50 ng/kg/day or 100 ng/kg/day). Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA) status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD) 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS) expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA) expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function.
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