Motor neuron degeneration is attenuated in bax-deficient neurons in vitro

O Bar-Peled; M Knudson; S J Korsmeyer; J D Rothstein

doi:10.1002/(SICI)1097-4547(19990301)55:5<542::AID-JNR2>3.0.CO;2-7

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Motor neuron degeneration is attenuated in bax-deficient neurons in vitro

Journal article

Peer reviewed

Motor neuron degeneration is attenuated in bax-deficient neurons in vitro

O Bar-Peled, M Knudson, S J Korsmeyer and J D Rothstein

Journal of neuroscience research, Vol.55(5), pp.542-556

03/01/1999

DOI: 10.1002/(SICI)1097-4547(19990301)55:5<542::AID-JNR2>3.0.CO;2-7

PMID: 10082077

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Abstract

Apoptosis plays a major role in motor neuron survival during developmental cell death, after axotomy, and in motor neuron diseases. Bax is the first member of the bcl-2 family shown to promote apoptosis. In the present study, we used the bax-deficient mouse model to determine the role of bax in motor neuron survival in vitro by using dissociated spinal cord cultures. This system enables the maturation of individual motor neurons in a controlled in vitro environment. Motor neurons were identified by using the antineurofilament antibody SMI-32 and the antitranscription factor antibody Islet1. Both antibodies labeled large motor neurons in wild-type and bax-null cultures. Differentiated wild-type cultures exhibited a reduction in long-term cultures of two- and fivefold in the number of SMI-32- and Islet1-positive cells, respectively. The reduction in the number of motor neurons was attenuated in bax -/- cultures. Bax deficiency also attenuated serum withdrawal- and kainate-induced apoptosis in motor neurons. For comparison, necrotic cell death led to significant motor neuron cell death in both wild-type and bax -/- cultures. In addition, bax deficiency did not induce proliferation of motor neuron precursors in vitro. This study indicates for the first time that bax has a dominant role in the survival of long-term cultured motor neurons.

Culture Media, Serum-Free

Male

Motor Neurons - pathology

Cell Nucleus - metabolism

Motor Neurons - cytology

Superoxides - metabolism

Female

Cell Death - drug effects

Spinal Cord - cytology

Paraquat - pharmacology

Motor Neurons - drug effects

Astrocytes - cytology

Cell Survival - drug effects

Kainic Acid - pharmacology

Cells, Cultured

Cell Size

Genotype

Proto-Oncogene Proteins - genetics

Proto-Oncogene Proteins - deficiency

bcl-2-Associated X Protein

Cell Division - drug effects

Motor Neurons - metabolism

Spinal Cord - embryology

Animals

Proto-Oncogene Proteins - physiology

Mice

Aspartic Acid - analogs & derivatives

Proto-Oncogene Proteins c-bcl-2

Cell Nucleus - drug effects

Nerve Degeneration

Kainic Acid - antagonists & inhibitors

Aspartic Acid - pharmacology

Astrocytes - metabolism

Details

Title: Subtitle: Motor neuron degeneration is attenuated in bax-deficient neurons in vitro
Creators: O Bar-Peled - Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287-7519, USA
M Knudson
S J Korsmeyer
J D Rothstein
Resource Type: Journal article
Publication Details: Journal of neuroscience research, Vol.55(5), pp.542-556
Publisher: United States
DOI: 10.1002/(SICI)1097-4547(19990301)55:5<542::AID-JNR2>3.0.CO;2-7
PMID: 10082077
ISSN: 0360-4012
eISSN: 1097-4547
Grant note: AG12992 / NIA NIH HHS NS34100 / NINDS NIH HHS NS33958 / NINDS NIH HHS
Language: English
Date published: 03/01/1999
Academic Unit: Pathology; Radiation Oncology
Record Identifier: 9984047783002771

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