title: TRPC6 inhibited NMDA receptor activities and protected neurons from ischemic excitotoxicity.
abstract: Excitotoxicity induced by NMDA receptor-mediated intracellular Ca(2+) ([Ca(2+) ](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 [Ca(2+)](i) elevation induced by NMDA and protected neurons from excitotoxicity. Over-expressing or down-regulating TRPC6 suppressed or aggravated Ca(2+) 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.
authors.affiliation: Laboratory of Neural Signal Transduction, Institute of Neuroscience, SIBS, State Key Laboratory of Neuroscience, Shanghai, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
authors.forename: Junbo
authors.initials: J
authors.lastname: Huang
authors.forename: Wanlu
authors.initials: W
authors.lastname: Du
authors.forename: Caixia
authors.initials: C
authors.lastname: Jia
authors.forename: Hailan
authors.initials: H
authors.lastname: Yao
authors.forename: Yizheng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000502:physiology*; D000074287:TRPC6 Cation Channel
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; C492145:Trpc6 protein, rat