TRPV4 Inhibition Improved Myelination and Reduced Glia Reactivity and Inflammation in a Cuprizone-Induced Mouse Model of Demyelination.
TRPV4 Inhibition Improved Myelination and Reduced Glia Reactivity and Inflammation in a Cuprizone-Induced Mouse Model of Demyelination.
复制标题
TRPV4 抑制可改善铜宗诱导的脱髓鞘小鼠模型中的髓鞘形成并减少神经胶质细胞反应性和炎症。
DOI：
10.3389/fncel.2018.00392
复制
发表时间：
2018
影响因子：
5.3
通讯作者：
Yao R
中科院分区：
文献类型：
--
作者：
Liu M;Liu X;Wang L;Wang Y;Dong F;Wu J;Qu X;Liu Y;Liu Z;Fan H;Yao R
The inhibition of demyelination and the promotion of remyelination are both considerable challenges in the therapeutic process for many central nervous system (CNS) diseases. Increasing evidence has demonstrated that neuroglial activation and neuroinflammation are responsible for myelin sheath damage during demyelinating disorders. It has been revealed that the nonselective cation channel transient receptor potential vanilloid 4 (TRPV4) profoundly affects a variety of physiological processes, including inflammation. However, its roles and mechanisms in demyelination have remained unclear. Here, for the first time, we found that there was a significant increase in TRPV4 in the corpus callosum in a demyelinated mouse model induced by cuprizone (CPZ). RN-1734, a TRPV4-antagonist, clearly alleviated demyelination and inhibited glial activation and the production of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) without altering the number of olig2-positive cells. In vitro, RN-1734 treatment clearly inhibited the influx of calcium and decreased the levels of IL-1β and TNF-α in lipopolysaccharide (LPS)-activated microglial cells by suppressing NF-κB P65 phosphorylation. Apoptosis of oligodendrocyte induced by LPS-activated microglia was also alleviated by RN-1734. The results suggest that activation of TRPV4 in microglia is involved in oligodendrocyte apoptosis through the activation of the NF-κB signaling pathway, thus revealing a new mechanism of CNS demyelination.
登录
查看更多内容
影响因子：
7.7
作者：
Harraz OF;Longden TA;Hill-Eubanks D;Nelson MT
通讯作者：
Nelson MT
影响因子：
3.7
作者：
Butenko O;Dzamba D;Benesova J;Honsa P;Benfenati V;Rusnakova V;Ferroni S;Anderova M
通讯作者：
Anderova M
局灶性皮质发育不良患者皮质病变中瞬时受体电位 Vanilloid 4 表达增加
影响因子：
5.5
作者：
Chen, Xin;Sun, Fei-Ji;Yang, Hui
通讯作者：
Yang, Hui
影响因子：
5.3
作者：
Hunt RF;Hortopan GA;Gillespie A;Baraban SC
通讯作者：
Baraban SC
DOI：
10.1007/978-3-642-54215-2_12
发表时间：
2014-01-01
期刊：
MAMMALIAN TRANSIENT RECEPTOR POTENTIAL (TRP) CATION CHANNELS, VOL I
影响因子：
--
作者：
Garcia-Elias, Anna;Mrkonjic, Sanela;Valverde, Miguel A.
通讯作者：
Valverde, Miguel A.