Neurobiology of vitamin C: Expanding the focus from antioxidant to endogenous neuromodulator (original) (raw)
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Ascorbic Acid and Its Role in Safeguarding Neurons: Updated Evidence
Ascorbic acid, commonly known as vitamin C, is a water-soluble vitamin synthesized in plants as well as many animal species, but not in humans. Humans obtain ascorbic acid from dietary sources and via vitamin supplementation. Ascorbic acid possesses important biological functions, including serving as a cofactor for many enzymes, acting as an antioxidant, and participating in regulating cell growth, apoptosis, and signaling, which collectively contribute to its essentialness in maintaining and safeguarding the physiological homeostasis and the health of human body. This article summarizes recent evidence for ascorbic acid acting as a booster in neuron physiology and a protector in neuron degeneration.
Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2
Free Radical Biology and Medicine, 2009
Ascorbate (vitamin C) is a vital antioxidant molecule in the brain. However, it also has a number of other important functions, participating as a co-factor in several enzyme reactions including catecholamine synthesis, collagen production and regulation of HIF-1α. 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 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 Huntingdon's disease.
Vitamin C in Health and Disease: Its Role in the Metabolism of Cells and Redox State in the Brain
Ever since Linus Pauling published his studies, the effects of vitamin C have been surrounded by contradictory results. This may be because its effects depend on a number of factors such as the redox state of the body, the dose used, and also on the tissue metabolism. This review deals with vitamin C pharmacokinetics and its participation in neurophysiological processes, as well as its role in the maintenance of redox balance. The distribution and the concentration of vitamin C in the organs depend on the ascorbate requirements of each and on the tissue distribution of sodium-dependent vitamin C transporter 1 and 2 (SVCT1 and SVCT2). This determines the specific distribution pattern of vitamin C in the body. Vitamin C is involved in the physiology of the nervous system, including the support and the structure of the neurons, the processes of differentiation, maturation, and neuronal survival; the synthesis of catecholamine, and the modulation of neurotransmission. This antioxidant interacts with self-recycling mechanisms, including its participation in the endogenous antioxidant system. We conclude that the pharmacokinetic properties of ascorbate are related to the redox state and its functions and effects in tissues.
AAA_Prooxidant versus antioxidant brain action of ascorbic acid_as a function of dose
Although ascorbic acid (AA) is an antioxidant, under certain conditions it can facilitate oxidation, which may underlie the opposite actions of AA on brain excitability in distinct seizure models. Here, we investigated whether chronic AA administration during brain development alters cortical excitability as a function of AA dose, as indexed by cortical spreading depression (CSD) and by the levels of lipid peroxidation-induced malondialdehyde. Well-nourished and early-malnourished rats received per gavage 30, 60, or 120 mg/kg/d of AA, saline, or no gavage treatment (naïve group) at postnatal days 7e28. CSD propagation and malondialdehyde levels were analyzed at 30e40 days. Confirming previous observations, CSD velocities were significantly higher in the early-malnourished groups than in the wellnourished groups. AA dose was important: 30 mg/kg/d AA decelerated CSD and reduced malondialdehyde levels, whereas 60 mg/kg/d and 120 mg/kg/d accelerated CSD and augmented malondialdehyde levels compared with the corresponding saline and naïve groups. Our findings reinforce previous suggestion that AA acts as an antioxidant in the brain when administered at low doses, but as a prooxidant at high doses, as indicated by CSD propagation and malondialdehyde levels.
The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism
Journal of Neurochemistry, 2014
Vitamin C is an essential factor for neuronal function and survival, existing in two redox states, ascorbic acid (AA), and its oxidized form, dehydroascorbic acid (DHA). Here, we show uptake of both AA and DHA by primary cultures of rat brain cortical neurons. Moreover, we show that most intracellular AA was rapidly oxidized to DHA. Intracellular DHA induced a rapid and dramatic decrease in reduced glutathione that was immediately followed by a spontaneous recovery. This transient decrease in glutathione oxidation was preceded by an increase in the rate of glucose oxidation through the pentose phosphate pathway (PPP), and a concomitant decrease in glucose oxidation through glycolysis. DHA stimulated the activity of glucose-6-phosphate dehydrogenase, the ratelimiting enzyme of the PPP. Furthermore, we found that DHA stimulated the rate of lactate uptake by neurons in a time-and dose-dependent manner. Thus, DHA is a novel modulator of neuronal energy metabolism by facilitating the utilization of glucose through the PPP for antioxidant purposes.
Nutrients
Ascorbic acid (AA; a.k.a. vitamin C) is well known for its cellular protection in environments of high oxidative stress. Even though physiological concentrations of AA in the brain are significant (0.2–10 mM), surprisingly little is known concerning the role of AA in synaptic neurotransmission under normal, non-disease state conditions. Here, we examined AA effects on neurotransmission, plasticity and spontaneous network activity (i.e., sharp waves and high frequency oscillations; SPW-HFOs), at the synapse between area 3 and 1 of the hippocampal cornu ammonis region (CA3 and CA1) using an extracellular multi-electrode array in in vitro mouse hippocampal slices. We found that AA decreased evoked field potentials (fEPSPs, IC50 = 0.64 mM) without affecting V50s or paired pulse facilitation indicating normal neurotransmitter release mechanisms. AA decreased presynaptic fiber volleys but did not change fiber volley-to-fEPSP coupling, suggesting reduced fEPSPs resulted from decreased fibe...
Evaluation of Pharmacologically Interesting Dose Range of Ascorbic Acid in Mice
Objective: Ascorbic acid is the most abundant water-soluble naturally occurring organic compound with antioxidant properties. It serves as a cofactor for enzymes involved in hormone biosynthesis, and the regeneration of antioxidants. Plants and food rich in ascorbic acid have been widely used in Ayurveda to treat a variety of psychologically stress related disorders.
Although ascorbic acid (AA) is an antioxidant, under certain conditions it can facilitate oxidation, which may underlie the opposite actions of AA on brain excitability in distinct seizure models. Here, we investigated whether chronic AA administration during brain development alters cortical excitability as a function of AA dose, as indexed by cortical spreading depression (CSD) and by the levels of lipid peroxidation-induced malondialdehyde. Well-nourished and early-malnourished rats received per gavage 30, 60, or 120 mg/kg/d of AA, saline, or no gavage treatment (naïve group) at postnatal days 7e28. CSD propagation and malondialdehyde levels were analyzed at 30e40 days. Confirming previous observations, CSD velocities were significantly higher in the early-malnourished groups than in the wellnourished groups. AA dose was important: 30 mg/kg/d AA decelerated CSD and reduced malondialdehyde levels, whereas 60 mg/kg/d and 120 mg/kg/d accelerated CSD and augmented malondialdehyde levels compared with the corresponding saline and naïve groups. Our findings reinforce previous suggestion that AA acts as an antioxidant in the brain when administered at low doses, but as a prooxidant at high doses, as indicated by CSD propagation and malondialdehyde levels.