TrkB mediates BDNF-induced potentiation of neuronal necrosis in cortical culture
Autor: | Hyun-Jung Kim, Jung Jin Hwang, M.Margarita Behrens, B.Joy Snider, Dennis W Choi, Jae-Young Koh |
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Jazyk: | angličtina |
Rok vydání: | 2003 |
Předmět: | |
Zdroj: | Neurobiology of Disease, Vol 14, Iss 1, Pp 110-119 (2003) |
Druh dokumentu: | article |
ISSN: | 1095-953X 0969-9961 |
DOI: | 10.1016/S0969-9961(03)00103-7 |
Popis: | In the present study, the signaling mechanisms underlying the effect of brain-derived neurotrophic factor (BDNF) on neuronal necrosis were investigated. Exposure of mature mouse cortical cultures (more than 10 days in vitro (DIV)) to 50–100 ng/ml BDNF for 48 h induced widespread neuronal necrosis that was antioxidant-sensitive. This neuronal necrosis was blocked by the selective NMDA antagonist MK-801, suggesting that prolonged BDNF exposure caused endogenous levels of NMDA receptor activation to become excitotoxic. We examined whether the p75NTR played a role in BDNF-induced neuronal death. However, p75NTR expression was low in cultured cortical cells, and neutralizing antibodies to p75NTR did not attenuate BDNF-triggered neuronal death. In contrast, trkB antisense oligonucleotides and inhibitors of Trk tyrosine kinase blocked BDNF-triggered neuronal death as well as BDNF potentiation of iron-induced oxidative neuronal necrosis, suggesting a critical role for TrkB in this phenomenon. Furthermore, BDNF did not potentiate neuronal necrosis in cortical cultures prepared from embryonic TrkB-null mice. These results suggest that TrkB plays an important role in BDNF-mediated neuronal necrosis. |
Databáze: | Directory of Open Access Journals |
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