title: CCL2 induces neural stem cell proliferation and neuronal differentiation in Niemann-Pick type C mice.
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.
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Hong
authors.forename: Hyun
authors.initials: H
authors.lastname: Lee
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Jong Kil
authors.initials: JK
authors.lastname: Lee
authors.forename: Ju Youn
authors.initials: JY
authors.lastname: Lee
authors.forename: Hwa Deok
authors.initials: HD
authors.lastname: Suh
authors.forename: Min Seock
authors.initials: MS
authors.lastname: Jeong
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Bae
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Jin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects*; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D017931:DNA Primers; D001973:Bromodeoxyuridine