RGD Reference Report - Exacerbation of facial motoneuron loss after facial nerve axotomy in CCR3-deficient mice. - Rat Genome Database

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Exacerbation of facial motoneuron loss after facial nerve axotomy in CCR3-deficient mice.

Authors: Wainwright, DA  Xin, J  Mesnard, NA  Beahrs, TR  Politis, CM  Sanders, VM  Jones, KJ 
Citation: Wainwright DA, etal., ASN Neuro. 2009 Dec 11;1(5):e00024.
RGD ID: 6892922
Pubmed: PMID:19922414   (View Abstract at PubMed)
PMCID: PMC2826103   (View Article at PubMed Central)
DOI: DOI:10.1042/AN20090017   (Journal Full-text)

We have previously demonstrated a neuroprotective mechanism of FMN (facial motoneuron) survival after facial nerve axotomy that is dependent on CD4(+) Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS (central nervous system)-resident microglia. PACAP (pituitary adenylate cyclase-activating polypeptide) is expressed by injured FMN and increases Th2-associated chemokine expression in cultured murine microglia. Collectively, these results suggest a model involving CD4(+) Th2 cell migration to the facial motor nucleus after injury via microglial expression of Th2-associated chemokines. However, to respond to Th2-associated chemokines, Th2 cells must express the appropriate Th2-associated chemokine receptors. In the present study, we tested the hypothesis that Th2-associated chemokine receptors increase in the facial motor nucleus after facial nerve axotomy at timepoints consistent with significant T-cell infiltration. Microarray analysis of Th2-associated chemokine receptors was followed up with real-time PCR for CCR3, which indicated that facial nerve injury increases CCR3 mRNA levels in mouse facial motor nucleus. Unexpectedly, quantitative- and co-immunofluorescence revealed increased CCR3 expression localizing to FMN in the facial motor nucleus after facial nerve axotomy. Compared with WT (wild-type), a significant decrease in FMN survival 4 weeks after axotomy was observed in CCR3(-/-) mice. Additionally, compared with WT, a significant decrease in FMN survival 4 weeks after axotomy was observed in Rag2(-/-) (recombination activating gene-2-deficient) mice adoptively transferred CD4(+) T-cells isolated from CCR3(-/-) mice, but not in CCR3(-/-) mice adoptively transferred CD4(+) T-cells derived from WT mice. These results provide a basis for further investigation into the co-operation between CD4(+) T-cell- and CCR3-mediated neuroprotection after FMN injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Facial Nerve Injuries  ISOCcr3 (Mus musculus)6892922; 6892922 RGD 
Facial Nerve Injuries  IMP 6892922 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr3  (C-C motif chemokine receptor 3)

Genes (Mus musculus)
Ccr3  (C-C motif chemokine receptor 3)

Genes (Homo sapiens)
CCR3  (C-C motif chemokine receptor 3)


Additional Information