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[P2.65]: p75NTR mediates the growth‐suppressing effects of semaphorins on sympathetic neurons: Mechanism for inhibiting axonal growth
Author(s) -
Naska S.,
Lin D.,
Miller F.,
Kaplan D.
Publication year - 2008
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2008.09.190
Subject(s) - sick child , miller , mechanism (biology) , medicine , semaphorin , citation , psychology , neuroscience , pediatrics , library science , computer science , philosophy , biology , epistemology , receptor , ecology
Calcium plays an essential role in endorsing neuronal growth and survival. Disturbances in neuronal calcium homeostasis have been implicated in a variety of neuropathological conditions, including Parkinson’s disease. Recently, several lines of evidence suggest that Ca influx through TRPC channel is required for neuronal protection. The mechanisms by which TRPC affects the neuronal survival process are not completely understood yet. Here, we report that depletion of membrane TRPC1 entailed neuronal apoptosis in C57BL/6 mice with different schedules of MPTP intoxication. The mRNA and protein expression of TRPC1 were evaluated using substantia nigra pars compacta (SNPc) from control and MPTP treated mice. The subacute and subchronic treatments with MPTP were shown to decrease tyrosine hydroxylase positive neurons and increase TUNEL positive neurons. Moreover, MPTP augmented the pro-apoptotic proteins such as, cytochrome c, caspase 3, caspase 9, Bax & Bak, reduced antiapoptotic proteins like, Bcl2 & Bcl-xl and induced endoplasmic reticulum (ER) stress markers. Using culture of human neuroblastoma cells, SH-SY5Y, we detected decrease in the expression of TRPC1 following MPP intoxication. The levels of pro-apoptotic proteins and ER stress markers increased whereas the antiapoptotic proteins significantly decreased during MPP treatment. Intriguingly, adeno-virus mediated over-expression of TRPC1 protected cells from apoptosis induced by MPP by improving anti-apoptotic proteins and preventing ER stress. Conclusion: These findings provide evidence that TRPC1 might have an important role in the survival of neurons.