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Role of brain‐derived neurotrophic factor in the protective action of N‐methyl‐D‐aspartate in the apoptotic death of cerebellar granule neurons induced by low potassium
Author(s) -
BazánPeregrino Miriam,
GutiérrezKobeh Laila,
Morán Julio
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21112
Subject(s) - nmda receptor , tropomyosin receptor kinase b , brain derived neurotrophic factor , neurotrophic factors , glutamate receptor , neurotrophin , neuroprotection , potassium , chemistry , tropomyosin receptor kinase a , pharmacology , programmed cell death , microbiology and biotechnology , receptor , biology , neuroscience , apoptosis , biochemistry , organic chemistry
Several neurotrophic factors, including brain‐derived neurotrophic factor (BDNF), and neurotransmitters, such as glutamate, may influence neuronal apoptotic death. Rat cerebellar granule neurons (CGN) cultured in low potassium (5 or 10 mM KCl) for more than 5 days in vitro (DIV) die apoptotically. These cells survive in the presence of high potassium (25 mM KCl, K25) or N‐methyl‐D‐aspartate (NMDA), an agonist of glutamatergic receptors. CGN transferred from high to low potassium die apoptotically. Here, we characterized the effect of BDNF and NMDA on the apoptotic death induced by low potassium in CGN. Cell death of CGN by culturing in low potassium for 6 DIV was inhibited by BDNF and NMDA. When CGN were cultured in K25 and transferred to a low‐potassium medium, 65% of neurons died after 48 hr. Under these conditions, BDNF, NMDA, or BDNF + NMDA increased CGN survival. Both BDNF and NMDA decreased caspase‐9 activity and mRNA caspase‐3 levels and activity induced by low potassium. CGN survival induced by BDNF is mediated by TrkB activation, whereas that induced by NMDA is mediated by NMDA receptor and TrkB activation. NMDA, but not BDNF, raised [Ca 2+ ] i , which was reduced by low‐potassium treatment. These results suggest that NMDA receptor stimulation induces CGN survival through the influx of extracellular Ca 2+ that may evoke the release of BDNF and the activation of TrkB. Complementary mechanisms induced by depolarization and changes in Ca 2+ levels would also contribute to the neuroprotection exerted by NMDA and potassium. © 2006 Wiley‐Liss, Inc.