Differential gene expression in the axotomized facial motor nucleus of presymptomatic SOD1 mice

Nichole A. Mesnard, Virginia M. Sanders, Kathryn J. Jones

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Previously, we compared molecular profiles of one population of wild-type (WT) mouse facial motoneurons (FMNs) surviving with FMNs undergoing significant cell death after axotomy. Regardless of their ultimate fate, injured FMNs respond with a vigorous pro-survival/regenerative molecular response. In contrast, the neuropil surrounding the two different injured FMN populations contained distinct molecular differences that support a causative role for glial and/or immune-derived molecules in directing contrasting responses of the same cell types to the same injury. In the current investigation, we utilized the facial nerve axotomy model and a presymptomatic amyotrophic lateral sclerosis (ALS) mouse (SOD1) model to experimentally mimic the axonal die-back process observed in ALS pathogenesis without the confounding variable of disease onset. Presymptomatic SOD1 mice had a significant decrease in FMN survival compared with WT, which suggests an increased susceptibility to axotomy. Laser microdissection was used to accurately collect uninjured and axotomized facial motor nuclei of WT and presymptomatic SOD1 mice for mRNA expression pattern analyses of pro-survival/pro-regeneration genes, neuropil-specific genes, and genes involved in or responsive to the interaction of FMNs and non-neuronal cells. Axotomized presymptomatic SOD1 FMNs displayed a dynamic pro-survival/regenerative response to axotomy, similar to WT, despite increased cell death. However, significant differences were revealed when the axotomy-induced gene expression response of presymptomatic SOD1 neuropil was compared with WT. We propose that the increased susceptibility of presymptomatic SOD1 FMNs to axotomy-induced cell death and, by extrapolation, disease progression, is not intrinsic to the motoneuron, but rather involves a dysregulated response by non-neuronal cells in the surrounding neuropil.

Original languageEnglish (US)
Pages (from-to)3488-3506
Number of pages19
JournalJournal of Comparative Neurology
Volume519
Issue number17
DOIs
StatePublished - Dec 1 2011

Fingerprint

Motor Neurons
Axotomy
Gene Expression
Neuropil
Cell Death
Amyotrophic Lateral Sclerosis
Genes
Facial Nucleus
Microdissection
Confounding Factors (Epidemiology)
Facial Nerve
Survival Analysis
Neuroglia
Population
Disease Progression
Regeneration
Lasers
Messenger RNA
Wounds and Injuries

Keywords

  • ALS
  • Facial nerve axotomy
  • Motoneuron
  • Neuropil
  • SOD1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Differential gene expression in the axotomized facial motor nucleus of presymptomatic SOD1 mice. / Mesnard, Nichole A.; Sanders, Virginia M.; Jones, Kathryn J.

In: Journal of Comparative Neurology, Vol. 519, No. 17, 01.12.2011, p. 3488-3506.

Research output: Contribution to journalArticle

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