NT-3 and BDNF protect CNS neurons against metabolic/excitotoxic insults.
Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) were recently shown to have biological activity in central neurons. In the present study, NT-3 and BDNF attenuated glucose deprivation-induced neuronal damage dose-dependently in rat hippocampal, septal and cortical cultures. Direct measurements of intraneuronal free calcium levels ([Ca2+]i) and manipulations of calcium influx demonstrated that NT-3 and BDNF each prevented the elevation of [Ca2+]i that mediated glucose deprivation-induced injury. Studies in cultures depleted of glia indicated a direct action of NT-3 and BDNF on neurons. Neurons pretreated with NT-3 or BDNF for 24 hr were more resistant to glutamate neurotoxicity, and showed attenuated [Ca2+]i responses to glutamate. TrkB (BDNF receptor) and trkC (NT-3 receptor) proteins were present in hippocampal, cortical and septal cultures where they were localized to neuronal cell bodies and neurites. The data demonstrate that NT-3 and BDNF can protect neurons against metabolic and excitotoxic insults, and suggest that these neurotrophins may serve [Ca2+]i-stabilizing and neuroprotective functions in the brain.
Cheng
B
B
Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536-0230.
Mattson
M P
MP
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D005947:Glucose / Q000502:physiology; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020933:Neurotrophin 3; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor / Q000096:biosynthesis
D019208:Brain-Derived Neurotrophic Factor; D003470:Culture Media; D005971:Glutamates; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor; D018698:Glutamic Acid; D020794:Receptor Protein-Tyrosine Kinases; D005947:Glucose; D002118:Calcium