BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities

• Published in: Brain research. Molecular brain research. Vol. 55; no. 1; pp. 20 - 27
• Main Authors: Lin, Siang-Yo, Wu, Kuo, Levine, Eric S, Mount, Howard T.J, Suen, Piin-Chau, Black, Ira B
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.03.1998; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - pharmacology; Cell physiology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - metabolism; Molecular and cellular biology; Nerve Tissue Proteins - metabolism; NMDA receptor; Organelles - drug effects; Organelles - metabolism; Phosphorylation - drug effects; Postsynaptic; Protein Processing, Post-Translational - drug effects; Protein-Tyrosine Kinases - metabolism; Rats; Rats, Sprague-Dawley; Receptor Protein-Tyrosine Kinases - drug effects; Receptor Protein-Tyrosine Kinases - physiology; Receptor, Ciliary Neurotrophic Factor; Receptors, N-Methyl-D-Aspartate - metabolism; Receptors, Nerve Growth Factor - drug effects; Receptors, Nerve Growth Factor - physiology; Responses to growth factors, tumor promotors, other factors; Stimulation, Chemical; Synapses - drug effects; Synapses - metabolism; Synapses - ultrastructure; Synaptic plasticity; trkB; Postsynaptic; Brain-derived neurotrophic factor; trkB; NMDA receptor; Synaptic plasticity; Tyrosine; Cerebral cortex; Phosphorylation; Rat; Rodentia; Central nervous system; Glutamate receptor; Subunit; Vertebrata; Mammalia; Postsynaptic density; Brain derived neurotrophic factor; Hippocampus; Brain (vertebrata)
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/S0169-328X(97)00349-5

While neurotrophins are critical for neuronal survival and differentiation, recent work suggests that they acutely regulate synaptic transmission as well. Brain-derived neurotrophic factor (BDNF) enhances excitatory postsynaptic currents in cultured dissociated hippocampal neurons within 2–3 min through postsynaptic, phosphorylation-dependent mechanisms. Moreover, BDNF modulates hippocampal long-term potentiation, in which postsynaptic NMDA ( N-methyl- d-aspartate) receptors (NRs) play a key role. We now report that BDNF acutely increases tyrosine phosphorylation of the specific NMDA receptor subunit NR2B, which has recently been shown to play a role in long-term potentiation. Incubation of BDNF with cortical or hippocampal postsynaptic densities for 5 min increased tyrosine phosphorylation of the NR2B subunits in a dose-dependent manner. A maximal increase to 165% of control phosphorylation occurred at a BDNF concentration of 2 ng/ml. The BDNF action appeared to be specific, since nerve growth factor, another member of the neurotrophin gene family, had no effect on NR2B phosphorylation. Further, BDNF action was selective, since it did not alter tyrosine phosphorylation of NR2A subunits. Our results suggest that tyrosine phosphorylation of NR2B subunits of the NMDA receptor may contribute to neurotrophin modulation of postsynaptic responsiveness and long-term potentiation.