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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2010

Open Access 01-12-2010 | Research

Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase

Authors: Amanda Emirandetti, Gustavo F Simões, Renata G Zanon, Alexandre LR Oliveira

Published in: Journal of Neuroinflammation | Issue 1/2010

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Abstract

Background

Astrocytes play a major role in preserving and restoring structural and physiological integrity following injury to the nervous system. After peripheral axotomy, reactive gliosis propagates within adjacent spinal segments, influenced by the local synthesis of nitric oxide (NO). The present work investigated the importance of inducible nitric oxide synthase (iNOS) activity in acute and late glial responses after injury and in major histocompatibility complex class I (MHC I) expression and synaptic plasticity of inputs to lesioned alpha motoneurons.

Methods

In vivo analyses were carried out using C57BL/6J-iNOS knockout (iNOS-/-) and C57BL/6J mice. Glial response after axotomy, glial MHC I expression, and the effects of axotomy on synaptic contacts were measured using immunohistochemistry and transmission electron microscopy. For this purpose, 2-month-old animals were sacrificed and fixed one or two weeks after unilateral sciatic nerve transection, and spinal cord sections were incubated with antibodies against classical MHC I, GFAP (glial fibrillary acidic protein - an astroglial marker), Iba-1 (an ionized calcium binding adaptor protein and a microglial marker) or synaptophysin (a presynaptic terminal marker). Western blotting analysis of MHC I and nNOS expression one week after lesion were also performed. The data were analyzed using a two-tailed Student's t test for parametric data or a two-tailed Mann-Whitney U test for nonparametric data.

Results

A statistical difference was shown with respect to astrogliosis between strains at the different time points studied. Also, MHC I expression by iNOS-/- microglial cells did not increase at one or two weeks after unilateral axotomy. There was a difference in synaptophysin expression reflecting synaptic elimination, in which iNOS-/- mice displayed a decreased number of the inputs to alpha motoneurons, in comparison to that of C57BL/6J.

Conclusion

The findings herein indicate that iNOS isoform activity influences MHC I expression by microglial cells one and two weeks after axotomy. This finding was associated with differences in astrogliosis, number of presynaptic terminals and synaptic covering of alpha motoneurons after lesioning in the mutant mice.
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Metadata
Title
Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase
Authors
Amanda Emirandetti
Gustavo F Simões
Renata G Zanon
Alexandre LR Oliveira
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2010
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-7-31

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