Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 59, Issue 12, Pages 1063-1069Publisher
AMER ASSN NEUROPATHOLOGISTS INC
DOI: 10.1093/jnen/59.12.1063
Keywords
astrocytes; inducible nitric oxide synthase; macrophage/microglia; very long chain fatty acids; X-adrenoleukodystrophy
Categories
Funding
- NINDS NIH HHS [NS-22576, NS-34741, NS-37766] Funding Source: Medline
Ask authors/readers for more resources
X-Adrenoleukodystrophy (X-ALD) is an inherited peroxisomal disorder of deficient catabolism of very long-chain (VLC) fatty acids with resulting neuroinflammatory demyelinating disease. Our recent documentation of nitric oxide (NO)mediated increase in VLC fatty acid levels in glial cells and demonstration of greater increase of VLC fatty acids levels in the inflammatory region (plaque) of X-ALD brain as compared to the normal-looking region away from the plaque prompted us to investigate the possible involvement of NO in the pathophysiology of X-ALD. Herein we provide evidence of the expression of inducible nitric oxide synthase (iNOS) in the CNS of X-ALD patients. In situ hybridization demonstrated that iNOS mRNA was present in brain tissues from X-ALD patients but not in normal controls. Double-labeling immunofluorescence studies using cell-specific markers confirmed that iNOS-expressing cells in the CNS of X-ALD were astrocytes and microglia/macrophages. Finally, antibodies against nitrotyrosine strongly immunoreacted with tissues from the center of the plaque region of X-ALD brains suggesting the presence of the NO reaction product nitrotyrosine in the CNS of X-ALD. Taken together, these results demonstrate that iNOS is expressed in the brains of patients with X-ALD and may contribute to the pathogenesis of the disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available