PMID- 17396124 OWN - NLM STAT- MEDLINE DCOM- 20070712 LR - 20161124 IS - 1097-6256 (Print) IS - 1097-6256 (Linking) VI - 10 IP - 5 DP - 2007 May TI - TRPC channels promote cerebellar granule neuron survival. PG - 559-67 AB - Channels formed by the transient receptor potential (TRP) family of proteins have a variety of physiological functions. Here we report that two members of the TRP cation channel (TRPC) subfamily, TRPC3 and 6, protected cerebellar granule neurons (CGNs) against serum deprivation-induced cell death in cultures and promoted CGN survival in rat brain. In CGN cultures, blocking TRPC channels or downregulating TRPC3 or 6 suppressed brain-derived neurotrophic factor (BDNF)-mediated protection, BDNF-triggered intracellular Ca2+ elevation and BDNF-induced CREB activation. By contrast, overexpressing TRPC3 or 6 increased CREB-dependent reporter gene transcription and prevented apoptosis in the neurons deprived of serum, and this protection was blocked by the dominant negative form of CREB. Furthermore, downregulating TRPC3 or 6 induced CGN apoptosis in neonatal rat cerebellum, and this effect was rescued by overexpressing either TRPC3 or 6. Thus, our findings provide in vitro and in vivo evidence that TRPC channels are important in promoting neuronal survival. FAU - Jia, Yichang AU - Jia Y AD - Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Key Laboratory of Neurobiology, Shanghai 200031, China. FAU - Zhou, Jian AU - Zhou J FAU - Tai, Yilin AU - Tai Y FAU - Wang, Yizheng AU - Wang Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070401 PL - United States TA - Nat Neurosci JT - Nature neuroscience JID - 9809671 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcium Channel Blockers) RN - 0 (Enzyme Inhibitors) RN - 0 (Imidazoles) RN - 0 (Neuroprotective Agents) RN - 0 (RNA, Small Interfering) RN - 0 (TRPC Cation Channels) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 3.4.22.- (Caspase 3) RN - I61V87164A (1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole) RN - SY7Q814VUP (Calcium) SB - IM CIN - Nat Neurosci. 2007 May;10(5):537-8. PMID: 17453053 MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Calcium/metabolism MH - Calcium Channel Blockers/pharmacology MH - Caspase 3/metabolism MH - Cell Survival/genetics/physiology MH - Cells, Cultured MH - Cerebellum/*cytology MH - Drug Interactions MH - Enzyme Inhibitors/pharmacology MH - Gene Expression Regulation/drug effects/*physiology MH - Green Fluorescent Proteins/metabolism MH - Imidazoles/pharmacology MH - In Situ Nick-End Labeling/methods MH - In Vitro Techniques MH - Neurons/drug effects/*physiology MH - Neuroprotective Agents/pharmacology MH - RNA, Small Interfering/pharmacology MH - Rats MH - TRPC Cation Channels/*physiology MH - Transfection/methods EDAT- 2007/03/31 09:00 MHDA- 2007/07/13 09:00 CRDT- 2007/03/31 09:00 PHST- 2006/10/23 00:00 [received] PHST- 2007/02/16 00:00 [accepted] PHST- 2007/03/31 09:00 [pubmed] PHST- 2007/07/13 09:00 [medline] PHST- 2007/03/31 09:00 [entrez] AID - nn1870 [pii] AID - 10.1038/nn1870 [doi] PST - ppublish SO - Nat Neurosci. 2007 May;10(5):559-67. doi: 10.1038/nn1870. Epub 2007 Apr 1.