Morphological changes and selective loss of motoneurons in the lumbar part of the spinal cord in a rat model of familial amyotrophic lateral sclerosis (fALS).
Morphological alterations and the course of changes in motoneuron counts were studied by light microscopy (cresyl violet staining) in the L2/L3 region of the spinal cord of hemizygotic transgenic rats carrying the amyotrophic lateral sclerosis-associated mutant human gene for Cu,Zn superoxide dismutase (hSOD1G93A) and of their non-transgenic littermates. In 60-day old transgenic rats, a few ischaemic-looking alpha-motoneurons and occasional vacuolization and accumulation of tigroid in some of the cells were apparent. On day 93 of life more distinct cellular pathology was found in transgenic rats, including moderate gliosis, neuronophagy of alpha-motoneurons, and occasional neuronophagy of gamma-motoneurons. In 120-day-old transgenic rats, abundant gliosis and profound neuronophagy of alpha-motoneurons were observed combined with occasional neuronophagy of other cells. Some loss of alpha-motoneurons was also apparent in 120-day-old non-transgenic littermates of the transgenic rats. No difference in alpha-motoneuron and gamma-motoneuron counts was found between the rats on day 60 of life (early presymptomatic stage of the model disease in the transgenic rats). At 93 days of age (late presymptomatic stage), alpha-motoneuron count, but not gamma-motoneuron count, tended to be lower (p=0.06) in the transgenic rats. On day 120 of life (symptomatic stage), alpha-motoneuron count in the transgenic rats was about half that in their nontransgenic littermates (p<0.001); at this time point the relative decline in alpha-motoneuron number in the former was 57% (day 120 versus day 60; p<0.001). A smaller decline in alpha-motoneuron count was also found in nontransgenic rats (day 120 vs day 60: 24%, p<0.05); this was not associated with the emergence of neurological symptoms or distinct changes in the cell morphology of the spinal cord region studied.
Gadamski
Roman
R
Department of Neuropathology, Polish Academy of Sciences Medical Research Centre, 5 Pawińskiego St, 02-106 Warsaw, Poland.
Chrapusta
Stanisław J
SJ
Wojda
Renata
R
Grieb
Paweł
P
D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008161:Lumbosacral Region; D008297:Male; D009046:Motor Neurons / Q000473:pathology*; D009154:Mutation; D051381:Rats; D013116:Spinal Cord / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1