Graduate School of Biomedical Science and Engineering, Hanyang Biomedical Research Institute, College of Medicine, Hanyang University, Seongdong-gu, Seoul, Republic of Korea.
Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seongdong-gu, Seoul, Republic of Korea.
Exp Mol Med. 2018 Mar 9;50(3):e455. doi: 10.1038/emm.2017.289.
Transient receptor potential vanilloid 1 (TRPV1) affects mood and neuroplasticity in the brain, where its role is poorly understood. In the present study we investigated whether capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide), an agonist of TRPV1, induced chromatin remodeling and thereby altered gene expression related to synaptic plasticity. We found that capsaicin treatment resulted in upregulation of histone deacetylase 2 (HDAC2) in the mouse hippocampus and HDAC2 was enriched at Psd95, synaptophysin, GLUR1, GLUR2 promoters. Viral-mediated hippocampal knockdown of HDAC2 induced expression of Synapsin I and prevented the detrimental effects of capsaicin on Synapsin I expression in mice, supporting the role of HDAC2 in regulation of capsaicin-induced Synapsin I expression. Taken together, our findings implicate HDAC2 in capsaicin-induced transcriptional regulation of synaptic molecules and support the view that HDAC2 is a molecular link between TRPV1 activity and synaptic plasticity.
瞬时受体电位香草酸 1 型（TRPV1）会影响大脑中的情绪和神经可塑性，但它的作用尚不清楚。在本研究中，我们研究了辣椒素（8-甲基-N-香草基-trans-6-壬酰胺），一种 TRPV1 的激动剂，是否会引起染色质重塑，从而改变与突触可塑性相关的基因表达。我们发现，辣椒素处理导致小鼠海马体中的组蛋白去乙酰化酶 2（HDAC2）上调，并且 HDAC2 在 Psd95、突触小泡蛋白、GLUR1、GLUR2 启动子处富集。海马体中 HDAC2 的病毒介导敲低诱导了突触核蛋白 I 的表达，并防止了辣椒素对小鼠突触核蛋白 I 表达的有害影响，支持了 HDAC2 在调节辣椒素诱导的突触核蛋白 I 表达中的作用。总之，我们的研究结果表明，HDAC2 参与了辣椒素诱导的突触分子的转录调节，并支持了 HDAC2 是 TRPV1 活性和突触可塑性之间的分子联系的观点。
