TRPC6 inhibited NMDA receptor activities and protected neurons from ischemic excitotoxicity
TRPC6 inhibited NMDA receptor activities and protected neurons from ischemic excitotoxicity
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DOI：
10.1111/jnc.12045
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发表时间：
2012-12-01
影响因子：
4.7
通讯作者：
Wang, Yizheng
中科院分区：
文献类型：
--
作者：
Li, Hongyu;Huang, Junbo;Wang, Yizheng
NMDA受体介导的细胞内Ca2+（[Ca2+]i）超载引起的兴奋毒性是脑缺血迟发性神经元死亡的主要原因。瞬时受体电位规范（TRPC）6保护神经元免受缺血性脑损伤。然而，TRPC 6保护神经元的机制在很大程度上是未知的。在这里，我们报道了TRPC 6抑制NMDA诱导的[Ca 2 +]i升高，并保护神经元免受兴奋性毒性。过度表达或下调TRPC 6分别抑制或加重兴奋性毒性下的Ca 2+超载。TRPC 6保护培养的神经元免受NMDA毒性或氧葡萄糖剥夺（OGD）引起的损伤。此外，TRPC 6转基因（Tg）小鼠的梗死体积小于野生型（WT）同窝仔。TRPC 6 Tg小鼠比其WT同窝小鼠具有更好的行为表现和更低的死亡率。因此，TRPC 6抑制NMDA受体触发的神经毒性，并保护神经元免受缺血性脑损伤。TRPC 6活性的增加可能是预防和治疗中风的潜在策略。
Excitotoxicity induced by NMDA receptor-mediated intracellular Ca2+ ([Ca2+]i) overload is a major cause of delayed neuronal death in cerebral ischemia. Transient receptor potential canonical (TRPC) 6 protects neurons from ischemic brain damage. However, the mechanisms by which TRPC6 protects neurons are largely unknown. Here, we reported that TRPC6 suppressed the [Ca2+]i elevation induced by NMDA and protected neurons from excitotoxicity. Over-expressing or down-regulating TRPC6 suppressed or aggravated Ca2+ overload under excitotoxicity, respectively. TRPC6 protected cultured neurons from damage caused by NMDA toxicity or oxygen glucose deprivation (OGD). Moreover, the infarct volume in TRPC6 transgenic (Tg) mice was smaller than that in wild-type (WT) littermates. The TRPC6 Tg mice had better behavior performance and lower mortality than their WT littermates. Thus, TRPC6 inhibited NMDA receptor-triggered neurotoxicity and protected neurons from ischemic brain damage. Increase in TRPC6 activity could be a potential strategy for stroke prevention and therapy.