Niacin-mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system

• DOI: 10.1007/s00401-020-02129-7
• Publication Date: 2020-02-06T14:03:22Z
• Authors: Khalil S. Rawji; Adam M.H. Young; Tanay Ghosh; Nathan J. Michaels; Reza Mirzaei; Janson Kappen; Kathleen L. Koleh...; Nima Alaeiilkhchi; Brian Lozinski; Manoj K. Mishra; Annie Pu; Weiwen Tang; Salma Zein; Deepak K. Kaushik; Michael B. Keough; Jason R. Plemel; Fiona Calvert; Andrew J. Knights; Daniel J. Gaffney; Wolfram Tetzlaff; Robin J. M. Franklin; V. Wee Yong
• Keywords: Remyelination; Scavenger Receptor; CD36

Abstract Remyelination following CNS demyelination restores rapid signal propagation and protects axons; however, its efficiency declines with increasing age. Both intrinsic changes in the oligodendrocyte progenitor cell population extrinsic factors lesion microenvironment of older subjects contribute to this decline. Microglia monocyte-derived macrophages are critical for successful remyelination, releasing growth clearing inhibitory myelin debris. Several studies have implicated delayed recruitment macrophages/microglia into lesions as a key contributor decline remyelination observed subjects. Here we show that decreased expression scavenger receptor CD36 aging mouse microglia human culture underlies their reduced phagocytic activity. Overexpression cultured rescues deficit phagocytosis By screening clinically approved agents stimulate macrophages/microglia, found niacin (vitamin B3) upregulates enhances by culture. This increase is mediated through (hydroxycarboxylic acid 2). Genetic fate mapping multiphoton live imaging systemic treatment 9–12-month-old demyelinated mice therapeutically relevant doses promotes debris clearance both peripherally derived microglia. accompanied enhancement numbers improved treated mice. Niacin represents safe translationally amenable regenerative therapy chronic demyelinating diseases such multiple sclerosis.