title: 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.
abstract: 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.
authors.affiliation: Neurodegeneration Research Group, The John P. Robarts Research Institute and The Department of Clinical Neurological Sciences, The University of Western Ontario, London, Canada.
authors.forename: B P
authors.initials: BP
authors.lastname: He
authors.forename: M J
authors.initials: MJ
authors.lastname: Strong
mesh_terms: 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
chemical_list: 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