NT-3 AND BDNF PROTECT CNS NEURONS AGAINST METABOLIC EXCITOTOXIC INSULTS

被引:352
作者
CHENG, B [1 ]
MATTSON, MP [1 ]
机构
[1] UNIV KENTUCKY, DEPT ANAT & NEUROBIOL, LEXINGTON, KY 40536 USA
关键词
CALCIUM; EXCITOTOXICITY; FURA-2; NEUROTROPHIN; TYROSINE KINASE; TRKB; TRKC;
D O I
10.1016/0006-8993(94)91857-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:56 / 67
页数:12
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