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

Grant number: 10/07471-0
Support type:Regular Research Grants - Publications - Scientific article
Duration: June 01, 2010 - November 30, 2010
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Alexandre Leite Rodrigues de Oliveira
Grantee:Alexandre Leite Rodrigues de Oliveira
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

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. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
EMIRANDETTI, AMANDA; SIMOES, GUSTAVO F.; ZANON, RENATA G.; OLIVEIRA, ALEXANDRE L. R. Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase. JOURNAL OF NEUROINFLAMMATION, v. 7, MAY 24 2010. Web of Science Citations: 11.

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