Research Article| Volume 162, ISSUE 2, P133-151, January 15, 1999

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

  • Yoon K. Sohn
    Division of Neuropathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Neema Ganju
    MGH East Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Kenneth D. Bloch
    Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Jack R. Wands
    MGH East Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Suzanne M. de la Monte
    Corresponding author. Tel.: +1-617-726-5602; fax: +1-617-726-5609
    MGH East Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Division of Neuropathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Alzheimer’s Disease Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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      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.


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