Nexus - 0705 - New Times Magazine-pages

Page Content (OCR)

In studies of animals exposed to repeated, mild episodes of not only resemble the characteristic neurofibrillary tangles of hypoxia (lack of brain oxygenation), it was found that such accu- Alzheimer's dementia but are immunologically identical as well.” mulated injuries can trigger biochemical changes that resemble Similarly, when experimental animals are exposed to the chemical those seen in Alzheimer's patients.” One of the effects of hypoxia MPTP they develop Parkinson's disorder; in fact, the older ani- is a massive release of glutamate into the space around the neu- mals develop the same inclusions (Lewy bodies) as seen in human ron, which results in the rapid death of these sensitised cells. As Parkinson's.” There is growing evidence that protracted gluta- we age, the blood supply to the brain is frequently impaired, mate toxicity leads to a condition of receptor loss characteristic of either because of atherosclerosis or repeated syncopal episodes, neurodegeneration.”’ This receptor loss produces a state of disin- leading to short periods of hypoxia. Hypoglycaemia produces hibition which magnifies excitotoxicity during the later stage of lesions very similar to hypoxia and via the same glutamate excito- the neurodegenerative process. toxic mechanism. In fact, recent studies of diabetics suffering from repeated episodes of hypoglycaemia associated with insulin | SPECIAL FUNCTIONS OF ASCORBIC ACID overmedication have demonstrated brain atrophy and dementia.” The brain contains one of the highest concentrations of ascorbic Another cause of isolated cerebral hypoglycaemia is the acid in the body. Most are aware of ascorbic acid's function in impaired transport of glucose into the brain across the blood-brain connective tissue synthesis and as a free radical scavenger, but it barrier. It is known that glucose enters the brain by way of a glu- has other functions that make it rather unique. cose transporter, and that in several conditions, including arte- In man, we know that certain areas of the brain have very high riosclerosis, Alzheimer's disease and ageing, this transporter is concentrations of ascorbic acid, such as the nucleus accumbens impaired.*'® This is especially and hippocampus. The lowest levels important in the diabetic, since pro- are seen in the substantia nigra. ’° longed elevation of the blood sugar There is now substantial evidence These levels seem to fluctuate with produces a down-regulation of the the electrical activity of the brain. glucose transporter and a concomi- that ascorbic acid modulates the Amphetamine acts to increase ascor- tant brain hypoglycaemia that is electrophysiological as well as bic acid concentration in the corpus ripimtignackticsicomen | behavioural functioning of scr (ws}neion ses) to type-I diabetics. the brain. This could mean that memory imprint area of the brain. a aca Sane, | a86Orbic acid holds great potential fst mown nn such as mitochondrial injury, in treating disease related to well. impaired cerebral blood flow, excitotoxic damage. One of the more interesting links is enzyme dysfunction and impaired between the secretion of the gluta- glucose transportation, develop mate neurotransmitter by the brain simultaneously. This greatly magni- and the release of ascorbic acid into fies excitotoxicity, leading to accelerated free radical injury, a the extracellular space.” This release of ascorbate can also be progressively rapid loss of cerebral function and profound induced by systemic administration of glutamate or aspartate, as changes in cellular energy production.® It is suspected that at would be seen in diets high in these excitotoxins. The other neu- least in some of the neurodegenerative diseases (in particular, rotransmitters do not have a similar effect on ascorbic acid Alzheimer's dementia and Parkinson's disease), this series of release. This effect appears to be an exchange mechanism; that is, events plays a major pathogenic role.“ Chronic free radical accu- the ascorbic acid and glutamate exchange places. Theoretically, mulation also results in an impaired functional reserve of antioxi- high concentration of ascorbic acid in the diet could inhibit gluta- dant vitamins/minerals, antioxidant enzymes (superoxide dismu- mate release, lessening the risk of excitotoxic damage. Of equal tase or SOD, catalase and glutathione peroxidase) and thiol com- importance is the free radical neutralising effect of ascorbic acid. pounds necessary for neural protection. Chronic unrelieved There is now substantial evidence that ascorbic acid modulates stress, chronic infection, free radical generating metals and toxins, the electrophysiological as well as behavioural functioning of the and impaired DNA repair enzymes all add to this damage. brain.” It also attenuates the behavioural response of rats exposed It is estimated that oxidative free radical injuries to DNA num- to amphetamine, which is known to act through an excitatory ber about 10,000 a day in humans.® Under conditions of cellular mechanism.” In part, this is due to the observed binding of ascor- stress, these may reach several hundred thousand. Normally, bic acid to the glutamate receptor. This could mean that ascorbic these injuries are repaired by special DNA repair enzymes. It is acid holds great potential in treating disease related to excitotoxic known that these repair enzymes decrease in number or become = damage. Thus far, there are no studies relating ascorbate metabo- less efficient as we age. Also, some individuals are born with lism in neurodegenerative diseases. There is at least one report of deficient repair enzymes, as in the case of xeroderma pigmento- ascorbic acid deficiency in guineas pigs producing histopathologi- sum, for example. Recent studies of Alzheimer's patients also cal changes similar to ALS.” demonstrate a significant deficiency in DNA repair enzymes and It is known that as we age there is a decline in brain levels of high levels of lipid peroxidation products in the affected parts of | ascorbate. When accompanied by a similar decrease in glu- the brain.’ It is important to realise that the hippocampus, most tathione peroxidase, we see an accumulation of H3O: and, hence, severely damaged in Alzheimer's dementia, is one of the areas of elevated levels of free radicals and lipid peroxidation. In one the brain most vulnerable to low glucose supply as well as low study it was found that, with age, not only does the extracellular oxygen supply. That also makes it very susceptible to concentration of ascorbic acid decrease but the capacity of the glutamate/free-radical toxicity. brain ascorbic acid system to respond to oxidative stress is Another interesting finding is that when cells are exposed to impaired as well.” glutamate, they develop certain inclusions (cellular debris) which In terms of its antioxidant activity, vitamins C and E interact in not only resemble the characteristic neurofibrillary tangles of Alzheimer's dementia but are immunologically identical as well.” Similarly, when experimental animals are exposed to the chemical MPTP they develop Parkinson's disorder; in fact, the older ani- mals develop the same inclusions (Lewy bodies) as seen in human Parkinson's.” There is growing evidence that protracted gluta- mate toxicity leads to a condition of receptor loss characteristic of neurodegeneration.”’ This receptor loss produces a state of disin- hibition which magnifies excitotoxicity during the later stage of the neurodegenerative process. There is now substantial evidence that ascorbic acid modulates the electrophysiological as well as behavioural functioning of the brain. This could mean that | ascorbic acid holds great potential in treating disease related to excitotoxic damage. NEXUS 43 AUGUST — SEPTEMBER 2000