Aggregates of mutant protein appear progressively in dendrites, in periaxonal processes of oligodendrocytes, and in neuronal and astrocytic perikarya of mice expressing the SOD1G93A mutation of familial amyotrophic lateral sclerosis
| Autor: | Nicholas K. Gonatas, Anna Stieber, Jacqueline O. Gonatas |
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| Rok vydání: | 2000 |
| Předmět: |
Pathology
medicine.medical_specialty Neurite Immunoelectron microscopy SOD1 Mice Transgenic Nerve Tissue Proteins Biology Immunoenzyme Techniques Mice Mutant protein medicine Animals Amyotrophic lateral sclerosis Cellular localization Neurons Superoxide Dismutase Amyotrophic Lateral Sclerosis Dendrites medicine.disease Spinal cord Immunohistochemistry Axons Astrogliosis Cell biology Microscopy Electron Oligodendroglia medicine.anatomical_structure Spinal Cord nervous system Neurology Astrocytes Mutation Neurology (clinical) |
| Zdroj: | Journal of the Neurological Sciences. 177:114-123 |
| ISSN: | 0022-510X |
| DOI: | 10.1016/s0022-510x(00)00351-8 |
| Popis: | Mice expressing the G93A and other mutations of Cu,Zn superoxide dismutase (SOD1G93A) are valid models for the familial form of amyotrophic lateral sclerosis (FALS) with SOD1 mutations and, probably, for sporadic ALS. Adult mice become progressively paralyzed and show most of the histopathological lesions reported in sporadic ALS, i.e. neuronal loss, astrogliosis, ubiquitin and Lewy body-like inclusions, dystrophic axons and fragmentation of the Golgi apparatus (GA) of motor neurons. In transgenic mice, the mutant protein and ubiquitin aggregate within pathological 13 nm thick filaments [Stieber A, Gonatas JO, Gonatas NK. J Neurol Sci 2000;173:53–62]. This immunocytochemical and quantitative study of mice expressing SOD1G93A establishes the chronological order and cellular localization of aggregates of SOD1 and their correlation with fragmentation of the GA. Young asymptomatic mice expressing SOD1G93A showed aggregates of mutant SOD1 within neurites, prior to the detection of SOD1 in the perikarya of spinal cord motor neurons and astrocytes. Both dendrites and the periaxonal oligodendroglial cytoplasm, surrounding atrophic axons, contained SOD1 as revealed by immunoelectron microscopy The perikarya of a small percentage of spinal cord motor neurons contained both fragmented GA and aggregates of SOD1; however, about 50% of motor neurons with fragmented GA did not contain SOD1 in the perikaryon, suggesting that aggregates of mutant protein may not directly cause fragmentation of the GA. The mechanism of the putative toxic effect by the mutant protein remains to be clarified. The isolation and biochemical characterization of the filamentous aggregates of mutant protein and ubiquitin from spinal cords of transgenic mice expressing mutations of the SOD1 gene may offer clues on pathogenetic mechanisms. |
| Databáze: | OpenAIRE |
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