Elsevier

Brain Research

Volume 640, Issues 1–2, 21 March 1994, Pages 56-67
Brain Research

NT-3 and BDNF protect CNS neurons against metabolic/excitotoxic insults

https://doi.org/10.1016/0006-8993(94)91857-0Get rights and content

Abstract

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 inlux 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 indicateda 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 localied 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.

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