New clues about vitamin D functions in the nervous system.
Accumulating data have provided evidence that 1 alpha,25 dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] is involved in brain function. Thus, the nuclear receptor for 1,25-(OH)(2)D(3) has been localized in neurons and glial cells. Genes encoding the enzymes involved in the metabolism of this hormone are also expressed in brain cells. The reported biological effects of 1,25-(OH)(2)D(3) in the nervous system include the biosynthesis of neurotrophic factors and at least one enzyme involved in neurotransmitter synthesis. 1,25-(OH)(2)D(3) can also inhibit the synthesis of inducible nitric oxide synthase and increase glutathione levels, suggesting a role for the hormone in brain detoxification pathways. Neuroprotective and immunomodulatory effects of this hormone have been described in several experimental models, indicating the potential value of 1,25-(OH)(2)D(3) pharmacological analogs in neurodegenerative and neuroimmune diseases. In addition, 1,25-(OH)(2)D(3) induces glioma cell death, making the hormone of potential interest in the management of brain tumors. These results reveal previously unsuspected roles for 1,25-(OH)(2)D(3) in brain function and suggest possible areas of future research.
Garcion
Emmanuel
E
INSERM ERIT-M 0104, 10 rue André Boquel, 49100 Angers, France.
Wion-Barbot
Nelly
N
Montero-Menei
Claudia N
CN
Berger
François
F
Wion
Didier
D
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002117:Calcitriol / Q000378:metabolism* / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009420:Nervous System / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; D018160:Receptors, Cytoplasmic and Nuclear; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D002117:Calcitriol; D005978:Glutathione