title: Cyclosporin A has direct effects on adult neural precursor cells.
abstract: Multipotent, self-renewing neural stem cells and their progeny [collectively referred to as neural precursor cells (NPCs)] represent a population of cells with great promise for CNS repair. To effectively harness their potential for therapeutic applications, the factors that regulate NPC behavior and/or fate must be well understood. The ability of immunomodulatory molecules to affect NPC behavior is of interest because of recent work elucidating the complex interactions between the immune system and nervous system. Herein, we examined the effects of cyclosporin A, a commonly used immunosuppressive molecule, on NPC proliferation kinetics, survival, and fate using in vitro assays at the population level and at the single-cell level. The use of pure populations of NPCs revealed a direct effect of cyclosporin A on cell survival, resulting in increased numbers and larger colonies, with no effect on proliferation kinetics. Cyclosporin A did not alter the differentiation profile of NPC colonies, indicating that it did not promote selective survival of a particular neural lineage. Additionally, we observed decreased cell-cell adhesions in developing cyclosporin A-treated NPC colonies. Consistent with the in vitro observations, in vivo administration of cyclosporin A to adult animals increased the numbers of NPCs within the neurogenic niche lining the lateral ventricles. Together, our findings establish that cyclosporin A has direct effects on NPCs both in vitro and in vivo, making it a promising candidate molecule for developing clinically relevant strategies to stimulate NPCs for brain repair.
authors.affiliation: Department of Surgery, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hunt
authors.forename: Allan
authors.initials: A
authors.lastname: Cheng
authors.forename: Amy
authors.initials: A
authors.lastname: Hoyles
authors.forename: Eric
authors.initials: E
authors.lastname: Jervis
authors.forename: Cindi M
authors.initials: CM
authors.lastname: Morshead
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000628:therapy; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020547:Lateral Ventricles / Q000166:cytology; D008297:Male; D051379:Mice; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine