NMDA receptor activation modulates programmed cell death during early post-natal retinal development: a BDNF-dependent mechanism |
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Authors: | Martins Rodrigo A P Silveira Mariana S Curado Marco R Police Angela I Linden Rafael |
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Institution: | Laboratorio de Neurogenese, Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro, Brazil. martinsr@biof.ufrj.br |
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Abstract: | Glutamate is a classical excitotoxin of the central nervous system (CNS), but extensive work demonstrates neuroprotective roles of this neurotransmitter in developing CNS. Mechanisms of glutamate-mediated neuroprotection are still under scrutiny. In this study, we investigated mediators of glutamate-induced neuroprotection, and tested whether this neurotransmitter controls programmed cell death in the developing retina. The protective effect of N-methyl-d-aspartate (NMDA) upon differentiating cells of retinal explants was completely blocked by a neutralizing antibody to brain-derived neurotrophic factor (BDNF), but not by an antibody to neurotrophin-4 (NT-4). Consistently, chronic activation of NMDA receptor increased the expression of BDNF and trkB mRNA, as well as BDNF protein content, but did not change the content of NT-4 mRNA in retinal tissue. Furthermore, we showed that in vivo inactivation of NMDA receptor by intraperitoneal injections of MK-801 increased natural cell death of specific cell populations of the post-natal retina. Our results show that chronic activation of NMDA receptors in vitro induces a BDNF-dependent neuroprotective state in differentiating retinal cells, and that NMDA receptor activation controls programmed cell death of developing retinal neurons in vivo. |
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Keywords: | amacrine cells development excitotoxicity glutamate neurotrophins programmed cell death |
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