title: Ultrastructural changes in lumbar spinal cord in transgenic SOD1G93A rats.
abstract: The purpose of this study was to determine structural changes which trigger the onset and progression of amyotrophic lateral sclerosis in rats expressing a human SOD1 transgene with mutation G93A. Lumbar spinal cord of affected rats in early and late presymptomatic (PM, 60 and 93 days of age) and symptomatic (S, 120 days of age) stage of the disease were analyzed ultrastructurally. At 60 days the structure of lumbar spinal cord as well as alpha motoneurons type S and F appeared normal; however, careful examination revealed that approximately 15% of axons were filled with mitochondria that were abnormal in number, size and morphology. Grossly swollen mitochondria with disrupted cristae were a prominent feature in all large axons at 93 days of age. At this time swelling and dilated mitochondria were observed also in type S motoneurons, while type F had small, well preserved mitochondria. At symptomatic stage the alpha motoneurons showed moderate neuronal loss, mainly of the S type. The most interesting finding at this stage was the occurrence of motoneurons with morphological signs of apoptotic-like degeneration. Such apoptotic-like motoneurons were characterized by nuclear and cytoplasmic condensation, chromatin compaction and formation of uniformly dense, dark structures. Numerous axons with very dark, compact interior as well as apoptotic bodies were irregularly scattered throughout the neuropil. Our ultrastructural study indicates that dying motoneurons in transgenic mutant SOD1G93A rats exhibit reminiscent apoptotic morphology which is preceded by significant mitochondrial abnormalities mainly in proximal axons and S motoneurons. Different reaction of slow and fast motoneurons to degenerating factors requires further analysis.
authors.affiliation: Neuromuscular Unit, Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St, 02-108 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Fidziańska
authors.forename: Roman
authors.initials: R
authors.lastname: Gadamski
authors.forename: Janina
authors.initials: J
authors.lastname: Rafałowska
authors.forename: Hanna
authors.initials: H
authors.lastname: Chrzanowska
authors.forename: Paweł
authors.initials: P
authors.lastname: Grieb
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology; D018450:Disease Progression; D006801:Humans; D008161:Lumbosacral Region; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure*; D009046:Motor Neurons / Q000473:pathology / Q000648:ultrastructure*; D009154:Mutation; D051381:Rats; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1