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NG2 cell response in the CNP-EGFP mouse after contusive spinal cord injury.

ABSTRACT: NG2(+) cells in the adult CNS are a heterogeneous population. The extent to which the subpopulation of NG2(+) cells that function as oligodendrocyte progenitor cells (OPCs) respond to spinal cord injury (SCI) and recapitulate their normal developmental progression remains unclear. We used the CNP-EGFP mouse, in which oligodendrocyte lineage cells express EGFP, to study NG2(+) cells in the normal and injured spinal cord. In white matter of uninjured mice, bipolar EGFP(+)NG2(+) cells and multipolar EGFP(neg)NG2(+) cells were identified. After SCI, EGFP(+)NG2(+) cell proliferation in residual white matter peaked at 3 days post injury (DPI) rostral to the epicenter, while EGFP(neg)NG2(+) cell proliferation peaked at 7 DPI at the epicenter. The expression of transcription factors, Olig2, Sox10, and Sox17, and the basic electrophysiological membrane parameters and potassium current phenotype of the EGFP(+)NG2(+) population after injury were consistent with those of proliferative OPCs during development. EGFP(neg)NG2(+) cells did not express transcription factors involved in oligodendrogenesis. EGFP(+)CC1(+) oligodendrocytes at 6 weeks included cells that incorporated BrdU during the peak of EGFP(+)NG2(+) cell proliferation. EGFP(neg)CC1(+) oligodendrocytes were never observed. Treatment with glial growth factor 2 and fibroblast growth factor 2 enhanced oligodendrogenesis and increased the number of EGFP(neg)NG2(+) cells. Therefore, based on EGFP and transcription factor expression, spatiotemporal proliferation patterns, and response to growth factors, two populations of NG2(+) cells can be identified that react to SCI. The EGFP(+)NG2(+) cells undergo cellular and physiological changes in response to SCI that are similar to those that occur in early postnatal NG2(+) cells during developmental oligodendrogenesis.

SUBMITTER: Lytle JM

PROVIDER: S-EPMC2696059 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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NG2 cell response in the CNP-EGFP mouse after contusive spinal cord injury.

Lytle Judith M JM Chittajallu Ramesh R Wrathall Jean R JR Gallo Vittorio V

Glia 20090201 3

NG2(+) cells in the adult CNS are a heterogeneous population. The extent to which the subpopulation of NG2(+) cells that function as oligodendrocyte progenitor cells (OPCs) respond to spinal cord injury (SCI) and recapitulate their normal developmental progression remains unclear. We used the CNP-EGFP mouse, in which oligodendrocyte lineage cells express EGFP, to study NG2(+) cells in the normal and injured spinal cord. In white matter of uninjured mice, bipolar EGFP(+)NG2(+) cells and multipola ...[more]

PMID: 18756526

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Project description:BackgroundWnt proteins are a large family of molecules that are critically involved in multiple central nervous system (CNS) developmental processes. Experimental evidences suggest a role for this family of proteins in many CNS disorders, including spinal cord injury (SCI), which is a major neuropathology owing to its high prevalence and chronic sensorimotor functional sequelae. Interestingly, most Wnt proteins and their inhibitors are expressed in the uninjured spinal cord, and their temporal expression patterns are dramatically altered after injury. However, little is known regarding the expression of their better-known receptors, the Frizzled family, after SCI. Thus, the aim of the present study was to evaluate the expression of Frizzled receptors in the damaged spinal cord.FindingsBased on the evidence that Wnts are expressed in the spinal cord and are transcriptionally regulated by SCI in adulthood, we analysed the spatio-temporal mRNA and protein expression patterns of Frizzled receptors after contusive SCI using quantitative RT-PCR and single and double immunohistochemistry, respectively. Our results show that almost all of the 10 known Frizzled receptors were expressed in specific spatial patterns in the uninjured spinal cords. Moreover, the Frizzled mRNAs and proteins were expressed after SCI, although their expression patterns were altered during the temporal progression of SCI. Finally, analysis of cellular Frizzled 5 expression pattern by double immunohistochemistry showed that, in the uninjured spinal cord, this receptor was expressed in neurons, oligodendrocytes, astrocytes, microglia and NG2(+) glial precursors. After injury, Frizzled 5 was not only still expressed in oligodendrocytes, astrocytes and NG2(+) glial precursors but also in axons at all evaluated time points. Moreover, Frizzled 5 was expressed in reactive microglia/macrophages from 3 to 14 days post-injury.ConclusionsOur data suggest the involvement of Frizzled receptors in physiological spinal cord function and in the cellular and molecular events that characterise its neuropathology.

Dataset Information

NG2 cell response in the CNP-EGFP mouse after contusive spinal cord injury.

Publications

NG2 cell response in the CNP-EGFP mouse after contusive spinal cord injury.

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