CCL2 induces neural stem cell proliferation and neuronal differentiation in Niemannpick type C mice

Yu Ri Hong, Hyun Lee, Min Hee Park, Jong Kil Lee, Ju Youn Lee, Hwa Deok Suh, Min Seock Jeong, Jae Sung Bae, Hee Kyung Jin

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)693-699
Number of pages7
JournalJournal of Veterinary Medical Science
Volume77
Issue number6
DOIs
StatePublished - 1 Jul 2015
Externally publishedYes

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