RGD Reference Report - Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system. - Rat Genome Database

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Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system.

Authors: Conti, G  Rostami, A  Scarpini, E  Baron, P  Galimberti, D  Bresolin, N  Contri, M  Palumbo, C  De Pol, A 
Citation: Conti G, etal., Exp Neurol. 2004 Jun;187(2):350-8.
RGD ID: 1580265
Pubmed: PMID:15144861   (View Abstract at PubMed)
DOI: DOI:10.1016/j.expneurol.2004.01.026   (Journal Full-text)

The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell-axon relationship causing axonal damage and regulating endoneurial cell life and death.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Autoimmune Neuritis  ISONos2 (Rattus norvegicus)1580265; 1580265protein:increased expression:nerve root more ...RGD 
Experimental Autoimmune Neuritis  IEP 1580265protein:increased expression:nerve root more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos2  (nitric oxide synthase 2)

Genes (Mus musculus)
Nos2  (nitric oxide synthase 2, inducible)

Genes (Homo sapiens)
NOS2  (nitric oxide synthase 2)

Additional Information