Chronic Treatment with Anti-bipolar Drugs Down Regulates Gene Expression of TRPC1 in Neurones
Chronic Treatment with Anti-bipolar Drugs Down Regulates Gene Expression of TRPC1 in Neurones
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抗双相情感障碍药物的长期治疗会下调神经元中 TRPC1 的基因表达
DOI：
10.3389/fncel.2016.00305
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发表时间：
2017-01-10
影响因子：
5.3
通讯作者：
Peng, Liang
中科院分区：
文献类型：
--
作者：
Du, Ting;Rong, Yan;Peng, Liang
在大脑中，TRPC 1通道在几乎所有区域的神经元中大量表达;这些蛋白质作为受体激活的离子通道发挥作用，并参与许多过程，对神经发生特别重要。原代培养的小鼠小脑颗粒细胞，大脑皮层神经元，和新鲜分离的神经元在体内大脑被用来研究慢性治疗与抗双相药物[卡马西平（CBZ），锂盐和丙戊酸]对TRPC 1基因表达的影响。RT-PCR检测TRPC 1 mRNA的表达，Western blotting检测蛋白质含量。钙池操作的质膜Ca 2+内流（SOCE）用基于Fura-2的显微荧光法测定。慢性治疗与三种药物下调mRNA和蛋白质表达在培养的小脑颗粒细胞在时间和浓度依赖性的方式。在用CBZ、锂盐和丙戊酸处理的培养的大脑皮层神经元中以及在从CBZ处理的动物的大脑新鲜分离的神经元中也观察到类似的效果。SOCE的幅度大幅下降，在小脑颗粒细胞慢性治疗的三种药物。我们的研究结果表明，下调TRPC 1基因表达和功能的神经元可能是抗双相情感药物的作用机制之一。
In the brain, TRPC1 channels are abundantly expressed in neurones virtually in all regions; these proteins function as receptor-activated ion channels and are implicated in numerous processes, being specifically important for neurogenesis. Primary cultures of mouse cerebellar granule cell, cerebral cortical neurones, and freshly isolated neurones from in vivo brains were used to study effects of chronic treatment with anti-bipolar drugs [carbamazepine (CBZ), lithium salts and valproic acid] on gene expression of TRPC1. Expression of TRPC1 mRNA was identified with reverse transcription-polymerase chain reaction, whereas protein content was determined by Western blotting. Store-operated plasmalemmal Ca2+ entry (SOCE) was measured with fura-2 based microfluorimetry. Chronic treatment with each of the three drugs down-regulated mRNA and protein expression in cultured cerebellar granule cells in a time- and concentration-dependent manner. Similar effect was also observed in cultured cerebral cortical neurones treated with CBZ, lithium salts and valproic acid and in freshly isolated neurones from the brains of CBZ-treated animals. The amplitude of SOCE was substantially decreased in cerebellar granule cells chronically treated with each of the three drugs. Our findings indicate that down-regulation of TRPC1 gene expression and function in neurones may be one of the mechanisms of anti-bipolar drugs action.