Biotelemetric monitoring of Vitamin C in the striatum of freely moving rats : study of its role in brain energetic metabolism

Ascorbic acid (AA) is water-soluble sugar acid commonly known as vitamin C. It is present in relatively high amounts in fresh fruit and vegetables and it is also added to pharmaceutical products and foodstuffs as antioxidant and stabilizer. Most mammals sintetize ascorbic acid from glucose in the liver where the enzyme L-gulonolactone oxidase is expressed. AA is not produced in human organism but introduced with diet. Vitamin C has a key role in several reactions such as collagen synthesis, carnitine synthesis, catecholamine synthesis, peptide amidation and tyrosine metabolism, AA−dependant hydroxylation of proline modifies collagen, strengthing blood vessels, skin, muscles and bones. AA, as radical scavenger against ROS and RNS, is the most important component of antioxidant pool in the brain. Furthermore, vitamin C is implicated in protection against excitotoxicity due to high glutamate concentration through ascorbate-glutamate hetero-exchange. Recently, Castro et al., proposed a new pivotal role for AA as modulator in the metabolic switch between glucose and lactate as energetic substrate of neurons. This review, mainly based on in-vitro results, summarizes the evidences of the relationships among glutamate, AA, glucose and lactate during neural activation. In this study we present the real-time monitoring of four striatal neurochemical species in conscious freely animals using implantable amperometric sensors interfaced to a biotelemetric device. The miniaturized device consisted of a single-supply sensor driver, a current-to-voltage converter, a microcontroller and a miniaturized data transmitter. Adult male Wistar rats (270-350 g) were uses in this study, housed under controlled conditions of temperature and light until stereotaxic surgery, performed under chloral hydrate anesthesia. Microsensors or biosensors were then inserted in the right striatum and the biotelemetric device fixed to the skull. The monitoring started 24 h after surgery. During the administration of a 5 min tail pinch, preformed in order to increase neuronal activity, an immediate increase of striatal AA and lactate currents was observed. Indeed, this physiological stimulation produced a significant decrease of glucose signal followed by its increase after stimulus suspension. It is important to remember that AA is oxidized to DHAA by ROS and RNS in neurons. DHAA, secreted in the extracellular space, enters astrocyte through GLUT1 transporter and is back-reduced to AA. A sustained increase of extracellular glucose could interfere with AA/DHAA cycle resulting in oxidative stress, AA loss and neuron damage. The previously-mentioned in-vivo results indicate that, during neuronal activation in physiological condition, extracellular striatal changes of the above neurochimicals mainly reflect astrocyte response to glutamatergic stimulation.