Department of Neurochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 9 Leontovicha str, Kiev, 01030, Ukraine.
Department of Molecular Oncogenetics, Institute of Molecular Biology and Genetics National Academy of Sciences of Ukraine, 150 Zabolotnogo Str, Kyiv, 03143, Ukraine.
Food Chem Toxicol. 2019 Jan;123:142-150. doi: 10.1016/j.fct.2018.10.054. Epub 2018 Oct 25.
Recent experimental and epidemiologic investigations have revealed that the central nervous system is a target for vitamin D3 action and also linked vitamin D3 deficiency to Alzheimer's and Parkinson's disease, autism and dementia. Abnormal homeostasis of glutamate and GABA and signaling disbalance are implicated in the pathogenesis of major neurological diseases. Here, key transport characteristics of glutamate and GABA were analysed in presynaptic nerve terminals (synaptosomes) isolated from the cortex of vitamin D3 deficient (VDD) rats. Puberty rats were kept at the VDD diet up to adulthood. VDD caused: (i) a decrease in the initial rates of L-[C]glutamate and [H]GABA uptake by plasma membrane transporters of nerve terminals; (ii) a decrease in exocytotic release of L-[C]glutamate and [H]GABA; (iii) changes in expression of glutamate (EAAC-1) and GABA (GAT-3) transporters. Whereas, the synaptosomal ambient levels and Ca-independent transporter-mediated release of L-[C]glutamate and [H]GABA were not significantly altered in VDD. Vitamin D3 is a potent neurosteroid and its nutritional deficiency can provoke development of neurological consequences changing glutamate/GABA transporter expressions and excitation/inhibition balance. Also, changes in glutamate transport can underlie lower resistance to hypoxia/ischemia, larger infarct volumes and worsened outcomes in ischemic stroke patients with VDD.
最近的实验和流行病学研究表明，中枢神经系统是维生素 D3 作用的靶点，维生素 D3 缺乏与阿尔茨海默病、帕金森病、自闭症和痴呆有关。谷氨酸和 GABA 的异常动态平衡和信号转导失衡与主要神经疾病的发病机制有关。在这里，分析了从维生素 D3 缺乏（VDD）大鼠皮层分离的突触体（突触体）中谷氨酸和 GABA 的关键转运特性。青春期大鼠在 VDD 饮食下维持至成年。VDD 导致：（i）神经末梢质膜转运体对 L-[C]谷氨酸和[H]GABA 摄取的初始速率降低；（ii）L-[C]谷氨酸和[H]GABA 的胞吐释放减少；（iii）谷氨酸（EAAC-1）和 GABA（GAT-3）转运体的表达改变。然而，VDD 并未显著改变突触体环境水平和 Ca 独立转运体介导的 L-[C]谷氨酸和[H]GABA 的释放。维生素 D3 是一种有效的神经甾体，其营养缺乏会引发神经后果，改变谷氨酸/GABA 转运体的表达和兴奋/抑制平衡。此外，谷氨酸转运的变化可能导致对缺氧/缺血的抵抗力降低、VDD 缺血性中风患者的梗死体积增大和预后恶化。
