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

J Neurochem. 2005 Oct;95(1):244-53. doi: 10.1111/j.1471-4159.2005.03360.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Animals, Newborn / growth & development
  • Animals, Newborn / physiology*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / physiology*
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • N-Methylaspartate / pharmacology
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / physiology
  • Neuroprotective Agents / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptor, trkB / genetics
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Retina / growth & development
  • Retina / physiology*


  • Brain-Derived Neurotrophic Factor
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Nerve Growth Factors
  • Neuroprotective Agents
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • Dizocilpine Maleate
  • Receptor, trkB
  • neurotrophin 4