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

作者：Hong Yu Ri; Lee Hyun; Park Min Hee; Lee Jong Kil; Lee Ju Youn; Suh Hwa Deok; Jeong Min Seock; Bae Jae Sung; Jin Hee Kyung^*

来源：Journal of Veterinary Medical Science, 2015, 77(6): 693-699.

DOI：10.1292/jvms.14-0352

• CCL2
• neural stem cell
• neurogenesis
• neuroinflammation
• Niemann-Pick Type C

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.

• 出版日期2015-6