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Spatiotemporal ablation of CXCR2 on oligodendrocyte lineage cells: Role in myelin repair.


ABSTRACT:

Background

Residual CXCR2 expression on CNS cells in Cxcr2 (+/-) ?Cxcr2 (-/-) chimeric animals slowed remyelination after both experimental autoimmune encephalomyelitis and cuprizone-induced demyelination.

Methods

We generated Cxcr2 (fl/-) :PLPCre-ER(T) mice enabling an inducible, conditional deletion of Cxcr2 on oligodendrocyte lineage cells of the CNS. Cxcr2 (fl/-) :PLPCre-ER(T) mice were evaluated in 2 demyelination/remyelination models: cuprizone-feeding and in vitro lysophosphatidylcholine (LPC) treatment of cerebellar slice cultures.

Results

Cxcr2 (fl/-) :PLPCre-ER(T)(+) (termed Cxcr2-cKO) mice showed better myelin repair 4 days after LPC-induced demyelination of cerebellar slice cultures. Cxcr2-cKOs also displayed enhanced hippocampal remyelination after a 2-week recovery from 6-week cuprizone feeding.

Conclusion

Using 2 independent demyelination/remyelination models, our data document enhanced myelin repair in Cxcr2-cKO mice, consistent with the data obtained from radiation chimerism studies of germline CXCR2. Further experiments are appropriate to explore how CXCR2 function in the oligodendrocyte lineage accelerates myelin repair.

SUBMITTER: Liu L 

PROVIDER: S-EPMC4676354 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Spatiotemporal ablation of CXCR2 on oligodendrocyte lineage cells: Role in myelin repair.

Liu LiPing L   Spangler Lisa C LC   Prager Briana B   Benson Bryan B   Hu BingQing B   Shi Samuel S   Love Anna A   Zhang CunJin C   Yu Meigen M   Cotleur Anne C AC   Ransohoff Richard M RM  

Neurology(R) neuroimmunology & neuroinflammation 20151119 6


<h4>Background</h4>Residual CXCR2 expression on CNS cells in Cxcr2 (+/-) →Cxcr2 (-/-) chimeric animals slowed remyelination after both experimental autoimmune encephalomyelitis and cuprizone-induced demyelination.<h4>Methods</h4>We generated Cxcr2 (fl/-) :PLPCre-ER(T) mice enabling an inducible, conditional deletion of Cxcr2 on oligodendrocyte lineage cells of the CNS. Cxcr2 (fl/-) :PLPCre-ER(T) mice were evaluated in 2 demyelination/remyelination models: cuprizone-feeding and in vitro lysophosp  ...[more]

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