Motor neuron-astrocyte interactions and levels of Cu,Zn superoxide dismutase in sporadic amyotrophic lateral sclerosis.
Copper, zinc superoxide dismutase (SOD1) is involved in neutralizing free radicals within cells, and mutant forms of the enzyme have recently been shown to occur in about 20% of familial cases of amyotrophic lateral sclerosis (ALS). To explore the mechanism of SOD1 involvement in ALS, we have analyzed SOD1 in sporadic ALS using activity assays and immunocyto-chemistry. Analyses of SOD1 activity in washed erythrocytes revealed no difference between 13 ALS cases and 4 controls. Spinal cord sections from 6 ALS cases, 1 primary lateral sclerosis (PLS) case, and 1 control case were stained using three different antibodies to SOD1. Since astrocytes are closely associated with motor neurons, antibodies to glial fibrillary acidic protein (GFAP) and vimentin were used as independent monitors of astrocytes. The principal findings from localizations are: (1) normal motor neurons do not have higher levels of SOD1 than other neurons, (2) there was no detectable difference in SOD1 levels in motor neurons of ALS cases and controls, (3) ALS spinal cord displayed a reduction or absence of SOD1-reactive astrocytes compared to the control and PLS cases, and (4) examination of GFAP-stained sections and morphometry showed that the normal close association between astrocytic processes and motor neuron somata was decreased in the ALS and PLS cases. These results indicate the disease mechanism in sporadic ALS may involve alterations in spinal cord astrocytes.
O'Reilly
S A
SA
Department of Biology, San Francisco State University, California, USA.
Roedica
J
J
Nagy
D
D
Hallewell
R A
RA
Alderson
K
K
Marklund
S L
SL
Kuby
J
J
Kushner
P D
PD
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000473:pathology; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology; D015415:Biomarkers; D002452:Cell Count; D004912:Erythrocytes / Q000201:enzymology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D008875:Middle Aged; D009046:Motor Neurons / Q000201:enzymology* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis*; D013116:Spinal Cord / Q000201:enzymology* / Q000473:pathology; D013482:Superoxide Dismutase / Q000032:analysis* / Q000172:deficiency
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D013482:Superoxide Dismutase