Crosstalk between brain-derived neurotrophic factor and N-methyl-D-aspartate receptor signaling in neurons

Glutamate is the major excitatory neurotransmitter in brain exerting prosurvival effect on neurons via N-methyl-D-aspartate receptor (NMDAR) signaling under physiological conditions. However in pathological circumstances such as ischemia, NMDARs might have proapoptotic excitotoxic activity. In contrast brain-derived neurotrophic factor (BDNF) signaling via tropomyosinrelated receptor kinase B (TrkB) has been largely considered to promote neuronal differentiation, plasticity and survival during normal development, and protect neurons in pathophysiological conditions antagonizing the NMDAR-mediated excitotoxic cell death. In this review we summarize recent evidence for the existent crosstalk and positive feedback loops between the BDNF and NMDAR signaling and point out some of the important specific features of each signaling pathway.Biomedical Reviews 2008; 19: 17-27