Minocycline Directly Enhances the Self-Renewal of Adult Neural Precursor Cells
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Minocycline not only has antibacterial action but also produces a variety of pharmacological effects. It has drawn considerable attention as a therapeutic agent for symptoms caused by inflammation in many neurological disorders, leading to several clinical trials. Although some of these effects are mediated through its function of suppressing microglial activation, it is not clear whether minocycline acts on other cell types in the adult brain. In this study, we utilized a colony-forming neurosphere assay, in which neural stem cells (NSCs) clonally proliferate to form floating colonies, called neurospheres. We found that minocycline (at therapeutically relevant concentrations in cerebrospinal fluid) enhances the self-renewal capability of NSCs derived from the subependymal zone of adult mouse brain and facilitates their differentiation into oligodendrocytes. Importantly, these effects were independent of a suppression of microglial activation and were specifically observed with minocycline (among tetracycline derivatives). In addition, the size of the NSC population in the adult brain was increased when minocycline was infused into the lateral ventricle by an osmotic minipump in vivo. While precise molecular mechanisms of how minocycline alters the behavior of adult NSCs remain unknown, our data provide a basis for the clinical use of minocycline to treat neurodegenerative and demyelinating diseases.
KeywordsNeural stem cell Self-renewal Oligodendrocyte Microglia
We thank K. Ono for O4 antibody, N. Kaneko and K. Sawamoto for discussion, and M. Mori and M. Tomoeda for technical assistance. This work was supported by Grants-in-Aid for Scientific Research (B) (16H04671) and for challenging Exploratory Research (16K14578) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (S. H.).
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