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

Bin Cheng; Mark P. Mattson

doi:10.1016/0006-8993(94)91857-0

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

Bin Cheng, Mark P. Mattson

Research output: Contribution to journal › Article › peer-review

350 Scopus citations

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.

Original language	English (US)
Pages (from-to)	56-67
Number of pages	12
Journal	Brain Research
Volume	640
Issue number	1-2
DOIs	https://doi.org/10.1016/0006-8993(94)91857-0
State	Published - Mar 21 1994
Externally published	Yes

Keywords

Calcium
Excitotoxicity
Fura-2
Neurotrophin
TrkB
TrkC
Tyrosine kinase

ASJC Scopus subject areas

Developmental Biology
Molecular Biology
Clinical Neurology
General Neuroscience

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10.1016/0006-8993(94)91857-0

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title = "NT-3 and BDNF protect CNS neurons against metabolic/excitotoxic insults",

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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AU - Cheng, Bin

AU - Mattson, Mark P.

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AB - 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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KW - Excitotoxicity

KW - Fura-2

KW - Neurotrophin

KW - TrkB

KW - TrkC

KW - Tyrosine kinase

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

Abstract

Keywords

ASJC Scopus subject areas

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