Neuritic sprouting with aberrant expression of the nitric oxide synthase III gene in neurodegenerative diseases

Neuronal loss, synaptic disconnection and neuritic sprouting correlate with dementia in Alzheimer's disease (AD). Nitric oxide (NO) is an important sy naptic plasticity molecule generated by nitric oxide synthase (NOS) oxidati on of a guanidino nitrogen of L-arginine. Experimentally, the NOS III gene is modulated with neuritic sprouting. In a previous study, NOS III expressi on was found to be abnormal in cortical neurons, white matter glial cells, and dystrophic neurites in AD and Down syndrome brains. The present study d emonstrates the same abnormalities in neuronal and glial NOS III expression with massive proliferation of NOS III-immunoreactive neurites and glial ce ll processes in other neurodegenerative diseases including: diffuse Lewy bo dy disease, Pick's disease, progressive supranuclear palsy, amyotrophic lat eral 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 neurodegenerati on. Double label immunohistochemical staining studies demonstrated nitrotyr osine and NOS III co-localized in only rare neurons and neuritic sprouts, s uggesting that peroxynitrite formation and nitration of growth cone protein s may not be important consequences of NOS III enzyme accumulation. The res ults suggest that aberrant NOS III expression and NOS III-associated neurit ic sprouting in the CNS are major abnormalities common to several important neurodegenerative diseases. (C) 1999 Elsevier Science BSI. All rights rese rved.