NMDA receptor activation modulates programmed cell death during early post-natal retinal development: a BDNF-dependent mechanism.

Rodrigo A P Martins; Mariana S Silveira; Marco R Curado; Angela I Police; Rafael Linden

doi:10.1111/j.1471-4159.2005.03360.x

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NMDA receptor activation modulates programmed cell death during early post-natal retinal development: a BDNF-dependent mechanism.

Rodrigo A P Martins·Mariana S Silveira·Marco R Curado·Angela I Police·Rafael Linden

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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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Aging Animals Animals, Newborn Apoptosis Brain-Derived Neurotrophic Factor Dizocilpine Maleate Excitatory Amino Acid Agonists Excitatory Amino Acid Antagonists N-Methylaspartate Nerve Growth Factors Neuroprotective Agents RNA, Messenger Rats Rats, Inbred Strains Receptor, trkB Receptors, N-Methyl-D-Aspartate Retina Journal Article Research Support, Non-U.S. Gov't

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Rodrigo A P Martins, Mariana S Silveira, Marco R Curado, Angela I Police, Rafael Linden. 2005. NMDA receptor activation modulates programmed cell death during early post-natal retinal development: a BDNF-dependent mechanism.. https://doi.org/10.1111/j.1471-4159.2005.03360.x

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