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Title: Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways
Authors: Almeida, R. D. 
Manadas, B. J. 
Melo, C. V. 
Gomes, J. R. 
Mendes, C. S. 
Grãos, M. M. 
Carvalho, R. F. 
Carvalho, A. P. 
Duarte, C. B. 
Keywords: BDNF; Apoptosis; Extracellular signal-regulated kinase (ERK); Phosphatidylinositol 3-kinase; Glutamate; Hippocampal neurons; Akt (PKB); Bcl-2
Issue Date: Oct-2005
Publisher: Nature Publishing Group
Citation: Cell Death and Differentiation. 12:10 (2005) 1329-1343
Abstract: Neurotrophins protect neurons against glutamate excitotoxicity, but the signaling mechanisms have not been fully elucidated. We studied the role of the phosphatidylinositol 3-kinase (PI3-K) and Ras/mitogen-activated protein kinase (MAPK) pathways in the protection of cultured hippocampal neurons from glutamate induced apoptotic cell death, characterized by nuclear condensation and activation of caspase-3-like enzymes. Pre-incubation with the neurotrophin brain-derived neurotrophic factor (BDNF), for 24 h, reduced glutamate-evoked apoptotic morphology and caspase-3-like activity, and transiently increased the activity of the PI3-K and of the Ras/MAPK pathways. Inhibition of the PI3-K and of the Ras/MAPK signaling pathways abrogated the protective effect of BDNF against glutamate-induced neuronal death and similar effects were observed upon inhibition of protein synthesis. Moreover, incubation of hippocampal neurons with BDNF, for 24 h, increased Bcl-2 protein levels. The results indicate that the protective effect of BDNF in hippocampal neurons against glutamate toxicity is mediated by the PI3-K and the Ras/MAPK signaling pathways, and involves a long-term change in protein synthesis
ISSN: 1350-9047
DOI: 10.1038/sj.cdd.4401662
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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