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The Journal of Neuroscience, 2001, 21:RC148:1-5

RAPID COMMUNICATION
Increased Expression of Neuronal Nitric Oxide Synthase Spliced Variants in Reactive Astrocytes of Amyotrophic Lateral Sclerosis Human Spinal Cord

Maria Vincenza Catania¹, Eleonora Aronica², Bulent Yankaya², and Dirk Troost²

¹ Institute of Bioimaging and Pathophysiology of the Central Nervous System, National Research Council, 95123 Catania, Italy, and ² Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

The expression of three different neuronal nitric oxide synthase (nNOS) spliced variants, named nNOS, nNOS, and nNOS, was investigated in the spinal cord of control and both familiar and sporadic amyotrophic lateral sclerosis (FALS and SALS) patients. Western blot analysis showed a consistent increase in nNOS expression in six SALS patients compared with controls when antibodies recognizing both nNOS and nNOS, or nNOS, nNOS, and nNOS were used, whereas no change was observed when a selective anti-nNOS antibody was used. Immunoreactivity signal for nNOS-- and nNOS- was equally present in ventral horn neurons of control and ALS spinal cord but was dramatically increased in reactive astrocytes of the ventral horn and white matter in both FALS and SALS. nNOS signal was equally expressed in motor neurons of normal and ALS spinal cord but was not evident in astrocytes. This finding indicates that nNOS and nNOS spliced variants are upregulated in reactive astrocytes in ALS. This may contribute to the peroxynitrite-mediated oxidative damage involved in the pathogenesis of both FALS and SALS.

Key words: amyotrophic lateral sclerosis; spinal cord; reactive astrocytes; nNOS; spliced variants; glia

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