Abstract
Neuronal loss, synaptic disconnection and neuritic sprouting correlate with dementia
in Alzheimer’s disease (AD). Nitric oxide (NO) is an important synaptic plasticity
molecule generated by nitric oxide synthase (NOS) oxidation of a guanidino nitrogen
of l-arginine. Experimentally, the NOS III gene is modulated with neuritic sprouting.
In a previous study, NOS III expression was found to be abnormal in cortical neurons,
white matter glial cells, and dystrophic neurites in AD and Down syndrome brains.
The present study demonstrates the same abnormalities in neuronal and glial NOS III
expression with massive proliferation of NOS III-immunoreactive neurites and glial
cell processes in other neurodegenerative diseases including: diffuse Lewy body disease,
Pick’s disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple
system atrophy, and Parkinson’s disease. However, each disease, including AD, was
distinguished by the selective alterations in NOS III expression and sprouting in
structures marred by neurodegeneration. Double label immunohistochemical staining
studies demonstrated nitrotyrosine and NOS III co-localized in only rare neurons and
neuritic sprouts, suggesting that peroxynitrite formation and nitration of growth
cone proteins may not be important consequences of NOS III enzyme accumulation. The
results suggest that aberrant NOS III expression and NOS III-associated neuritic sprouting
in the CNS are major abnormalities common to several important neurodegenerative diseases.
Keywords
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Article info
Publication history
Accepted:
October 16,
1998
Received in revised form:
August 19,
1998
Received:
April 14,
1998
Identification
Copyright
© 1999 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
