PMID- 17086548 OWN - NLM STAT- MEDLINE DCOM- 20070329 LR - 20131121 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 85 IP - 2 DP - 2007 Feb 1 TI - 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. PG - 332-41 AB - 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. FAU - Bazan-Peregrino, Miriam AU - Bazan-Peregrino M AD - Departamento de Neurociencias, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Mexico D.F., Mexico. FAU - Gutierrez-Kobeh, Laila AU - Gutierrez-Kobeh L FAU - Moran, Julio AU - Moran J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (RNA, Messenger) RN - 6384-92-5 (N-Methylaspartate) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 9) RN - RWP5GA015D (Potassium) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Apoptosis/*physiology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Calcium/metabolism MH - Caspase 3/metabolism MH - Caspase 9/metabolism MH - Cells, Cultured MH - Cerebellum/metabolism/pathology MH - Immunoblotting MH - N-Methylaspartate/*metabolism MH - Neurons/*metabolism/physiology MH - Neuroprotective Agents/*metabolism MH - Potassium/*metabolism MH - RNA, Messenger/analysis MH - Rats MH - Receptor, trkB/metabolism EDAT- 2006/11/07 09:00 MHDA- 2007/03/30 09:00 CRDT- 2006/11/07 09:00 PHST- 2006/11/07 09:00 [pubmed] PHST- 2007/03/30 09:00 [medline] PHST- 2006/11/07 09:00 [entrez] AID - 10.1002/jnr.21112 [doi] PST - ppublish SO - J Neurosci Res. 2007 Feb 1;85(2):332-41. doi: 10.1002/jnr.21112.