Motor neuronal death in sporadic amyotrophic lateral sclerosis (ALS) is not apoptotic. A comparative study of ALS and chronic aluminium chloride neurotoxicity in New Zealand white rabbits.
Whether diseased motor neurones in sporadic amyotrophic lateral sclerosis (ALS) die via apoptosis is unknown. Because this relates primarily to difficulties in utilizing post-mortem tissue from end-stage disease, motor neurone degeneration in ALS spinal cord was compared with that of a model of a chronic motor neurone degeneration. Degenerating motor neurones in ALS, identified by ubiquitin immunoreactivity, did not demonstrate the morphological characteristics of apoptosis and were not c-Jun immunoreactive or TUNEL positive. A temporal analysis of spinal motor neurone death in the chronic AlCl3 neurotoxicity model of motor neurone degeneration was also undertaken. AlCl3 was administered intracisternally every 4 weeks and, at intervals of 51, 107, 156 and 267 days, evidence of apoptosis was sought by morphology, TUNEL hybridization or DNA laddering. Double-labelling immunostudies were also performed with antibodies to either c-Jun, ubiquitin or high molecular weight neurofilament (NFH) with TUNEL hybridization. Although significant neurone loss was evident, apoptosis was not found. These studies demonstrate a lack of apoptosis in ALS spinal motor neurones and suggest that this observation does not relate to the utilization of post-mortem tissue in which apoptotic neurones may have been lost.
He
B P
BP
Neurodegeneration Research Group, The John P. Robarts Research Institute and The Department of Clinical Neurological Sciences, The University of Western Ontario, London, Canada.
Strong
M J
MJ
D000328:Adult; D000368:Aged; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced* / Q000473:pathology*; D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D001252:Astringents / Q000633:toxicity*; D002712:Chlorides / Q000633:toxicity*; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000737:chemistry / Q000473:pathology*; D016900:Neurofilament Proteins / Q000032:analysis / Q000276:immunology; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000276:immunology; D011817:Rabbits; D013116:Spinal Cord / Q000473:pathology; D014452:Ubiquitins / Q000032:analysis / Q000276:immunology
D017607:Aluminum Compounds; D000911:Antibodies, Monoclonal; D001252:Astringents; D002712:Chlorides; D016900:Neurofilament Proteins; D016755:Proto-Oncogene Proteins c-jun; D014452:Ubiquitins; C051774:neurofilament protein H; D000077410:Aluminum Chloride