Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2.
Ascorbate (vitamin C) is a vital antioxidant molecule in the brain. However, it also has a number of other important functions, participating as a cofactor in several enzyme reactions, including catecholamine synthesis, collagen production, and regulation of HIF-1 alpha. Ascorbate is transported into the brain and neurons via the sodium-dependent vitamin C transporter 2 (SVCT2), which causes accumulation of ascorbate within cells against a concentration gradient. Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose transporters of the GLUT family. Once in cells, it is rapidly reduced to ascorbate. The highest concentrations of ascorbate in the body are found in the brain and in neuroendocrine tissues such as adrenal, although the brain is the most difficult organ to deplete of ascorbate. Combined with regional asymmetry in ascorbate distribution within different brain areas, these facts suggest an important role for ascorbate in the brain. Ascorbate is proposed as a neuromodulator of glutamatergic, dopaminergic, cholinergic, and GABAergic transmission and related behaviors. Neurodegenerative diseases typically involve high levels of oxidative stress and thus ascorbate has been posited to have potential therapeutic roles against ischemic stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease.
Harrison
Fiona E
FE
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6303, USA.
May
James M
JM
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000502:physiology* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000737:chemistry / Q000502:physiology* / Q000627:therapeutic use; D001692:Biological Transport; D001921:Brain / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D009474:Neurons / Q000473:pathology / Q000502:physiology; D029363:Organic Anion Transporters, Sodium-Dependent / Q000502:physiology*; D018384:Oxidative Stress; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D000975:Antioxidants; D029363:Organic Anion Transporters, Sodium-Dependent; C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D001205:Ascorbic Acid