title: 1,25-Dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation.
abstract: 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has recently been found to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Although its effect was attributed to an anti-inflammatory mechanism, it is not clear whether this treatment can also directly act on neural cells to promote CNS recovery. The present study investigates the effect of various concentrations of 1,25(OH)2D3 on neural stem cell (NSC) proliferation and their differentiation to oligodendrocytes, the myelinating cells. We have, for the first time, shown that NSCs constitutively express vitamin D receptor (VDR), which can be upregulated by 1,25(OH)2D3. This vitamin significantly enhanced proliferation of NSCs, and enhanced their differentiation into neurons and oligodendrocytes, but not astrocytes. NSCs treated with 1,25(OH)2D3 showed increased expression of NT-3, BDNF, GDNF and CNTF, important neurotrophic factors for neural cell survival and differentiation. Overall, we demonstrated that 1,25(OH)2D3 has a direct effect on NSC proliferation, survival, and neuron/oligodendrocyte differentiation, thus representing a novel mechanism underlying its remyelinating and neuroprotective effect in MS/EAE therapy.
authors: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, United States.
authors: Hasti Atashi
authors: HA
authors: Shirazi
authors: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, United States.
authors: Javad
authors: J
authors: Rasouli
authors: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, United States.
authors: Bogoljub
authors: B
authors: Ciric
authors: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, United States.
authors: Abdolmohamad
authors: A
authors: Rostami
authors: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, United States. Electronic address: guang-xian.zhang@jefferson.edu.
authors: Guang-Xian
authors: GX
authors: Zhang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy; D009414:Nerve Growth Factors / Q000096:biosynthesis; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020933:Neurotrophin 3; D009836:Oligodendroglia / Q000166:cytology*; D018167:Receptors, Calcitriol / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; C000595808:NTF3 protein, human; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D018167:Receptors, Calcitriol; C579455:BDNF protein, human; D002117:Calcitriol
keywords: 1,25-Dihydroxyvitamin D(3); Neural differentiation; Neural stem cells