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Brain‐derived neurotrophic factor inhibits cell cycle reentry but not endoplasmic reticulum stress in cultured neurons following oxidative or excitotoxic stress
Author(s) -
Boutahar Nadia,
Reynaud Evelyne,
Lassabliere François,
Borg Jacques
Publication year - 2010
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.22384
Subject(s) - neuroprotection , microbiology and biotechnology , endoplasmic reticulum , neurotrophic factors , brain derived neurotrophic factor , glutamate receptor , neurotrophin , nmda receptor , programmed cell death , excitotoxicity , mapk/erk pathway , biology , chemistry , neuroscience , kinase , apoptosis , biochemistry , receptor
Neurotrophins protect neurons against glutamate and oxidative stress, but the underlying mechanism remains unclear. We investigated the neuroprotective role of the neurotrophin brain‐derived neurotrophic factor (BDNF) in neuronal cultures subjected to NMDA or H 2 O 2 toxicity and analyzed the molecular mechanisms involved, particularly those related to regulation of cell cycle or endoplasmic reticulum (ER) stress. Preincubation with BDNF of cortical neuron cultures prevented NMDA‐ or H 2 O 2 ‐induced neuronal death as well as MAPK‐ERK1/2 activation. Inhibition of phosphatidylinositol 3‐kinase (PI3‐K) abolished the protective effect of BDNF. NMDA and H 2 O 2 induced activation of cell cycle reentry regulators such as retinoblastoma (Rb) protein and E2F1 transcription factor. However, BDNF abolished the activation of both factors. NMDA‐induced expression of chaperone encoding gene BIP was slightly inhibited by BDNF, but it did not affect expression of ER stress protein CHOP. Our results suggest that BDNF neuroprotection may be mediated through inhibition of Ras‐MAPK pathway and cell cycle reentry during oxidative or excitotoxic stress responses. However, BDNF did not modify expression of ER stress signal induced by NMDA. © 2010 Wiley‐Liss, Inc.