Requirement for BDNF in activity-dependent survival of cortical neurons.
Cultured embryonic cortical neurons from rats were used to explore mechanisms of activity-dependent neuronal survival. Cell survival was increased by the activation of voltage-sensitive calcium channels (VSCCs) but not by activation of N-methyl-D-aspartate receptors. These effects correlated with the expression of brain-derived neurotrophic factor (BDNF) induced by these two classes of calcium channels. Antibodies to BDNF (which block intracellular signaling by BDNF, but not by nerve growth factor, NT3, or NT4/5) reduced the survival of cortical neurons and reversed the VSCC-mediated increase in survival. Thus, endogenous BDNF is a trophic factor for cortical neurons whose expression is VSCC-regulated and that functions in the VSCC-dependent survival of these neurons.
Ghosh
A
A
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
Carnahan
J
J
Greenberg
M E
ME
D000818:Animals; D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004622:Embryo, Mammalian; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D016202:N-Methylaspartate / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015398:Signal Transduction
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D017362:Cyclic AMP Response Element-Binding Protein; D005971:Glutamates; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D011189:Potassium Chloride