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CCL2 induces neural stem cell proliferation and neuronal differentiation in Niemann-Pick type C mice.

Hong YR, Lee H, Park MH, Lee JK, Lee JY, Suh HD, Jeong MS, Bae JS, Jin HK - J. Vet. Med. Sci. (2015)

Bottom Line: Targeting of neuronal cells in the brain therefore represents a potential clinical intervention strategy to reduce the rate of disease progression and improve the quality of life.However, the direct effect of CCL2 on neurogenesis has not been ascertained.CCL2-treated NSCs showed significantly increased capacity for self-renewal, proliferation and neuronal differentiation.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea.

ABSTRACT
Niemann-Pick type C disease (NP-C) is a rare and ultimately fatal lysosomal storage disorder with variable neurologic symptoms. Loss of neuronal function and neuronal cell death occur in the NP-C brain, similar to the findings for other neurodegenerative diseases. Targeting of neuronal cells in the brain therefore represents a potential clinical intervention strategy to reduce the rate of disease progression and improve the quality of life. We previously reported that bone marrow stem cells show a neurogenic effect through CCL2 (also known as monocyte chemoattractant protein-1, MCP-1) secretion in the brains of NP-C mice. However, the direct effect of CCL2 on neurogenesis has not been ascertained. Here, to define neurogenic effects of CCL2 in NP-C, we applied human recombinant CCL2 to neural stem cells (NSCs) derived from NP-C mice. CCL2-treated NSCs showed significantly increased capacity for self-renewal, proliferation and neuronal differentiation. Similar results were observed in the subventricular zone of NP-C mice after CCL2 treatment. Furthermore, infusion of CCL2 into the NP-C mouse brain resulted in reduction of neuroinflammation. Taken together, our results demonstrate that CCL2 is a potential new therapeutic agent for NP-C.

No MeSH data available.


Related in: MedlinePlus

CCL2 ameliorates neuroinflammation in NP-C mice. (A) Representative images andquantification of GFAP on days 7 and 28 after CCL2 treatment (scale bar, 100µm, n=3 per group). Quantification of GFAP immunostaining foractivated astrocyte cells was performed in the striatum, cortex and thalamus. (B)Expression of anti-inflammatory cytokines (IL-10 and IL-4) and pro-inflammatorycytokines (IL-1β, IL-6 and TNF-α) was measured by quantitative real time PCR in thebrain region of CCL2 injection (striatum close to the SVZ). The expression of thedifferent genes was normalized by GAPDH (n=4 per group). All data are given as mean ±SEM. *P<0.05, **P<0.01***P<0.005.
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fig_004: CCL2 ameliorates neuroinflammation in NP-C mice. (A) Representative images andquantification of GFAP on days 7 and 28 after CCL2 treatment (scale bar, 100µm, n=3 per group). Quantification of GFAP immunostaining foractivated astrocyte cells was performed in the striatum, cortex and thalamus. (B)Expression of anti-inflammatory cytokines (IL-10 and IL-4) and pro-inflammatorycytokines (IL-1β, IL-6 and TNF-α) was measured by quantitative real time PCR in thebrain region of CCL2 injection (striatum close to the SVZ). The expression of thedifferent genes was normalized by GAPDH (n=4 per group). All data are given as mean ±SEM. *P<0.05, **P<0.01***P<0.005.

Mentions: CCL2 ameliorates neuroinflammation in NP-C mice: To investigate whethertreatment of CCL2 affects glial cell activation, we examined astrocyte activation in NP-Cmice using GFAP staining. Astrocyte activation was significantly higher in the brains ofNP-C mice than in those of WT mice, but decreased in the brains of CCL2-treated NP-C mice(Fig. 4AFig. 4.


CCL2 induces neural stem cell proliferation and neuronal differentiation in Niemann-Pick type C mice.

Hong YR, Lee H, Park MH, Lee JK, Lee JY, Suh HD, Jeong MS, Bae JS, Jin HK - J. Vet. Med. Sci. (2015)

CCL2 ameliorates neuroinflammation in NP-C mice. (A) Representative images andquantification of GFAP on days 7 and 28 after CCL2 treatment (scale bar, 100µm, n=3 per group). Quantification of GFAP immunostaining foractivated astrocyte cells was performed in the striatum, cortex and thalamus. (B)Expression of anti-inflammatory cytokines (IL-10 and IL-4) and pro-inflammatorycytokines (IL-1β, IL-6 and TNF-α) was measured by quantitative real time PCR in thebrain region of CCL2 injection (striatum close to the SVZ). The expression of thedifferent genes was normalized by GAPDH (n=4 per group). All data are given as mean ±SEM. *P<0.05, **P<0.01***P<0.005.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488406&req=5

fig_004: CCL2 ameliorates neuroinflammation in NP-C mice. (A) Representative images andquantification of GFAP on days 7 and 28 after CCL2 treatment (scale bar, 100µm, n=3 per group). Quantification of GFAP immunostaining foractivated astrocyte cells was performed in the striatum, cortex and thalamus. (B)Expression of anti-inflammatory cytokines (IL-10 and IL-4) and pro-inflammatorycytokines (IL-1β, IL-6 and TNF-α) was measured by quantitative real time PCR in thebrain region of CCL2 injection (striatum close to the SVZ). The expression of thedifferent genes was normalized by GAPDH (n=4 per group). All data are given as mean ±SEM. *P<0.05, **P<0.01***P<0.005.
Mentions: CCL2 ameliorates neuroinflammation in NP-C mice: To investigate whethertreatment of CCL2 affects glial cell activation, we examined astrocyte activation in NP-Cmice using GFAP staining. Astrocyte activation was significantly higher in the brains ofNP-C mice than in those of WT mice, but decreased in the brains of CCL2-treated NP-C mice(Fig. 4AFig. 4.

Bottom Line: Targeting of neuronal cells in the brain therefore represents a potential clinical intervention strategy to reduce the rate of disease progression and improve the quality of life.However, the direct effect of CCL2 on neurogenesis has not been ascertained.CCL2-treated NSCs showed significantly increased capacity for self-renewal, proliferation and neuronal differentiation.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea.

ABSTRACT
Niemann-Pick type C disease (NP-C) is a rare and ultimately fatal lysosomal storage disorder with variable neurologic symptoms. Loss of neuronal function and neuronal cell death occur in the NP-C brain, similar to the findings for other neurodegenerative diseases. Targeting of neuronal cells in the brain therefore represents a potential clinical intervention strategy to reduce the rate of disease progression and improve the quality of life. We previously reported that bone marrow stem cells show a neurogenic effect through CCL2 (also known as monocyte chemoattractant protein-1, MCP-1) secretion in the brains of NP-C mice. However, the direct effect of CCL2 on neurogenesis has not been ascertained. Here, to define neurogenic effects of CCL2 in NP-C, we applied human recombinant CCL2 to neural stem cells (NSCs) derived from NP-C mice. CCL2-treated NSCs showed significantly increased capacity for self-renewal, proliferation and neuronal differentiation. Similar results were observed in the subventricular zone of NP-C mice after CCL2 treatment. Furthermore, infusion of CCL2 into the NP-C mouse brain resulted in reduction of neuroinflammation. Taken together, our results demonstrate that CCL2 is a potential new therapeutic agent for NP-C.

No MeSH data available.


Related in: MedlinePlus