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Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase.
J Neuroinflammation. 2010 May 24; 7:31.JN

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.

Authors+Show Affiliations

Department of Anatomy, Institute of Biology, University of Campinas (UNICAMP), CP 6109, CEP 13083-970, Campinas, SP, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20497552

Citation

Emirandetti, Amanda, et al. "Spinal Motoneuron Synaptic Plasticity After Axotomy in the Absence of Inducible Nitric Oxide Synthase." Journal of Neuroinflammation, vol. 7, 2010, p. 31.
Emirandetti A, Simões GF, Zanon RG, et al. Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase. J Neuroinflammation. 2010;7:31.
Emirandetti, A., Simões, G. F., Zanon, R. G., & Oliveira, A. L. (2010). Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase. Journal of Neuroinflammation, 7, 31. https://doi.org/10.1186/1742-2094-7-31
Emirandetti A, et al. Spinal Motoneuron Synaptic Plasticity After Axotomy in the Absence of Inducible Nitric Oxide Synthase. J Neuroinflammation. 2010 May 24;7:31. PubMed PMID: 20497552.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase. AU - Emirandetti,Amanda, AU - Simões,Gustavo F, AU - Zanon,Renata G, AU - Oliveira,Alexandre L R, Y1 - 2010/05/24/ PY - 2009/09/04/received PY - 2010/05/24/accepted PY - 2010/5/26/entrez PY - 2010/5/26/pubmed PY - 2010/9/24/medline SP - 31 EP - 31 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 7 N2 - 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. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/20497552/Spinal_motoneuron_synaptic_plasticity_after_axotomy_in_the_absence_of_inducible_nitric_oxide_synthase_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-7-31 DB - PRIME DP - Unbound Medicine ER -