Document Detail

DL-Homocysteic acid application disrupts calcium homeostasis and induces degeneration of spinal motor neurons in vivo.
MedLine Citation:
PMID:  11935257     Owner:  NLM     Status:  MEDLINE    
Excitotoxicity, autoimmunity and free radicals have been postulated to play a role in the pathomechanism of amyotrophic lateral sclerosis (ALS), the most frequent motor neuron disease. Altered calcium homeostasis has already been demonstrated in Cu/Zn superoxide dismutase transgenic animals, suggesting a role for free radicals in the pathogenesis of ALS, and in passive transfer experiments, modeling autoimmunity. These findings also suggested that yet-confined pathogenic insults, associated with ALS, could trigger the disruption of calcium homeostasis of motor neurons. To test the possibility that excitotoxic processes may also be able to increase calcium in motor neurons, we applied the glutamate analogue DL-homocysteic acid to the spinal cord of rats in vivo and analyzed the calcium distribution of the motor neurons over a 24-h survival period by electron microscopy. Initially, an elevated cytoplasmic calcium level, with no morphological sign of degeneration, was noticed. Later, increasing calcium accumulation was seen in different cellular compartments with characteristic features of alteration at different survival times. This calcium accumulation in organelles was paralleled by their progressive degeneration, which culminated in cell death by the end of the observation time. These findings confirm that increased calcium also plays a role in excitotoxic lesion of motor neurons, in line with previous studies documenting the involvement of calcium ions in motor neuronal injury in other models of the disease as well as elevated calcium in biopsy samples from ALS patients. We suggest that intracellular calcium might be responsible for the interplay between the different pathogenic processes resulting in a uniform clinicopathological picture of the disease.
Róbert Adalbert; József I Engelhardt; László Siklós
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-02-23
Journal Detail:
Title:  Acta neuropathologica     Volume:  103     ISSN:  0001-6322     ISO Abbreviation:  Acta Neuropathol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-04-05     Completed Date:  2002-06-21     Revised Date:  2007-11-09    
Medline Journal Info:
Nlm Unique ID:  0412041     Medline TA:  Acta Neuropathol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  428-36     Citation Subset:  IM    
Institute of Biophysics, Biological Research Center, P.O. Box 521, 6701 Szeged, Hungary.
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MeSH Terms
Amyotrophic Lateral Sclerosis / pathology*,  physiopathology
Anterior Horn Cells / drug effects,  pathology*,  ultrastructure
Calcium / metabolism*
Calcium Signaling / drug effects,  physiology*
Cell Death / drug effects,  physiology
Disease Models, Animal
Glutamic Acid / metabolism
Homeostasis / drug effects,  physiology*
Homocysteine / analogs & derivatives*,  pharmacology*
Microscopy, Electron
Rats, Inbred Strains
Reg. No./Substance:
1001-13-4/homocysteic acid; 454-28-4/Homocysteine; 56-86-0/Glutamic Acid; 7440-70-2/Calcium

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