ENHANCED SUPEROXIDE DISMUTASE-2 IMMUNOREACTIVITY OF ASTROCYTES AND OCCASIONAL NEURONS IN AMYOTROPHIC-LATERAL-SCLEROSIS

The recent discovery of missense mutations in the superoxide dismutase (SOD)-1 gene as a cause of familial amyotrophic lateral sclerosis (AL S) and the ensuing description of transgenic SOD-1 mutant mouse models have focussed scientific interest on free radical scavenging mechanis ms in all other familial (FALS) and sporadic (SALS) forms of the disea se. We have compared the presence of intracellular cytosolic copper-zi nc SOD-I and mitochondrial manganese SOD-2 in the CNS from FALS and SA LS patients and from non-neurological controls by immunohistochemical assessment,in the knowledge that no SOD-1 mutations have been found in any of 18 Dutch ALS pedigrees. ALS specimens from the motor cortex an d the spinal cord presented enhanced SOD-2 immunoreactivity, especiall y of astrocytes and occasionally of neurons, Astrocyte staining appear ed to be increased at the cerebral cortical and the spinal cervical an d lumbar levels, but was only slightly increased in the thoracic anter ior horns and not at all in the brain stem. This indicates that, by th e time of death, the disease had burnt out in the brain stem and thora cic cord, Increased staining of neurons was limited to the small later al and dorsal nuclei of the spinal cord. FALS and SALS cases exhibited the same staining patterns. SOD-I immunoreactivity did not differ bet ween disease and control specimens. SOD-I and -2 staining was normal i n the ALS cortical, brain stem and spinal motoneurons. This suggests t hat SALS and non-SOD-l mutant FALS are not accompanied by loss of SOD- I or 2 protein. An enzyme-linked immunosorbent assay revealed no diffe rences in SOD-I and SOD-2 levels between ALS patients and controls. Ou r major finding of locally increased SOD-2 immunoreactivity of astrocy tes in FALS and SALS specimens, probably reflects reactive fibrillary and protoplasmatic gliosis in areas of ongoing degeneration but may al so result from an attempt at compensation for free radical injury.