Dataset Information

Effects of facial nerve axotomy on Th2- and Th1-associated chemokine expression in the facial motor nucleus of wild-type and presymptomatic mSOD1 mice.

ABSTRACT: We have previously demonstrated a neuroprotective mechanism of facial motoneuron (FMN) survival after facial nerve axotomy that is dependent on CD4(+) Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS resident microglia. To investigate this mechanism, we chose to study the Th2-associated chemokine, CCL11, and Th1-associated chemokine, CXCL11, in wild-type and presymptomatic mSOD1 mice after facial nerve axotomy. In this report, the results indicate that CCL11 is constitutively expressed in the uninjured facial motor nucleus, but CXCL11 is not expressed at all. Facial nerve axotomy induced a shift in CCL11 expression from FMN to astrocytes, whereas CXCL11 was induced in FMN. Differences in the number of CCL11- and CXCL11-expressing cells were observed between WT and mSOD1 mice after facial nerve axotomy.

SUBMITTER: Wainwright DA

PROVIDER: S-EPMC2783706 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Effects of facial nerve axotomy on Th2- and Th1-associated chemokine expression in the facial motor nucleus of wild-type and presymptomatic mSOD1 mice.

Wainwright Derek A DA Xin Junping J Mesnard Nichole A NA Politis Christine M CM Sanders Virginia M VM Jones Kathryn J KJ

Journal of neuroimmunology 20091008 1-2

We have previously demonstrated a neuroprotective mechanism of facial motoneuron (FMN) survival after facial nerve axotomy that is dependent on CD4(+) Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS resident microglia. To investigate this mechanism, we chose to study the Th2-associated chemokine, CCL11, and Th1-associated chemokine, CXCL11, in wild-type and presymptomatic mSOD1 mice after facial nerve axotomy. In this report, the results indicate that CCL11 is const ...[more]

PMID: 19818514

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Project description:When facial nerve axotomy (FNA) is performed on immunodeficient recombinase activating gene-2 knockout (RAG-2-/-) mice, there is greater facial motoneuron (FMN) death relative to wild type (WT) mice. Reconstituting RAG-2-/- mice with whole splenocytes rescues FMN survival after FNA, and CD4+ T cells specifically drive immune-mediated neuroprotection. Evidence suggests that immunodysregulation may contribute to motoneuron death in amyotrophic lateral sclerosis (ALS). Immunoreconstitution of RAG-2-/- mice with lymphocytes from the mutant superoxide dismutase (mSOD1) mouse model of ALS revealed that the mSOD1 whole splenocyte environment suppresses mSOD1 CD4+ T cell-mediated neuroprotection after FNA. The objective of the current study was to characterize the effect of CD4+ T cells on the central molecular response to FNA and then identify if mSOD1 whole splenocytes blocked these regulatory pathways. Gene expression profiles of the axotomized facial motor nucleus were assessed from RAG-2-/- mice immunoreconstituted with either CD4+ T cells or whole splenocytes from WT or mSOD1 donors. The findings indicate that immunodeficient mice have suppressed glial activation after axotomy, and cell transfer of WT CD4+ T cells rescues microenvironment responses. Additionally, mSOD1 whole splenocyte recipients exhibit an increased astrocyte activation response to FNA. In RAG-2-/- + mSOD1 whole splenocyte mice, an elevation of motoneuron-specific Fas cell death pathways is also observed. Altogether, these findings suggest that mSOD1 whole splenocytes do not suppress mSOD1 CD4+ T cell regulation of the microenvironment, and instead, mSOD1 whole splenocytes may promote motoneuron death by either promoting a neurotoxic astrocyte phenotype or inducing Fas-mediated cell death pathways. This study demonstrates that peripheral immune status significantly affects central responses to nerve injury. Future studies will elucidate the mechanisms by which mSOD1 whole splenocytes promote cell death and if inhibiting this mechanism can preserve motoneuron survival in injury and disease.

Dataset Information

Effects of facial nerve axotomy on Th2- and Th1-associated chemokine expression in the facial motor nucleus of wild-type and presymptomatic mSOD1 mice.

Publications

Effects of facial nerve axotomy on Th2- and Th1-associated chemokine expression in the facial motor nucleus of wild-type and presymptomatic mSOD1 mice.

Similar Datasets

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