Document Detail


Motor neuron degeneration is attenuated in bax-deficient neurons in vitro.
MedLine Citation:
PMID:  10082077     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
O Bar-Peled; M Knudson; S J Korsmeyer; J D Rothstein
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  55     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-05-24     Completed Date:  1999-05-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  542-56     Citation Subset:  IM    
Affiliation:
Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287-7519, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspartic Acid / analogs & derivatives,  pharmacology
Astrocytes / cytology,  metabolism
Cell Death / drug effects
Cell Division / drug effects
Cell Nucleus / drug effects,  metabolism
Cell Size
Cell Survival / drug effects
Cells, Cultured
Culture Media, Serum-Free
Female
Genotype
Kainic Acid / antagonists & inhibitors,  pharmacology
Male
Mice
Motor Neurons / cytology,  drug effects,  metabolism,  pathology*
Nerve Degeneration*
Paraquat / pharmacology
Proto-Oncogene Proteins / deficiency,  genetics,  physiology*
Proto-Oncogene Proteins c-bcl-2*
Spinal Cord / cytology,  embryology
Superoxides / metabolism
bcl-2-Associated X Protein
Grant Support
ID/Acronym/Agency:
AG12992/AG/NIA NIH HHS; NS33958/NS/NINDS NIH HHS; NS34100/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Bax protein, mouse; 0/Culture Media, Serum-Free; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 11062-77-4/Superoxides; 1860-87-3/3-hydroxyaspartic acid; 4685-14-7/Paraquat; 487-79-6/Kainic Acid; 56-84-8/Aspartic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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