One of the effects common to many anti-seizure medications and therapies is fluidization of brain membranes. Membrane fluidity is influenced by many factors, some of which are cholesterol content, fatty acid profile, and degree of lipid peroxidation. The higher the cholesterol content, the more rigid and impermeable membranes become. The more polyunsaturated the fatty acid profile, the more fluid they become. And peroxidization, a potential risk factor in DS, decreases membrane fluidity.
Brain membranes may be especially sensitive to changes in membrane fluidity. They have an especially high degree of polyunsaturation, containing high levels of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), which have 5 and 6 double bonds respectively. These highly unsaturated fatty acids increase the fluidity of brain membranes, but they also make them especially sensitive to free radicals and oxidative stress, a putative risk factor resulting from overexpression of superoxide dismutase (SOD), an antioxidant enzyme which is encoded on the 21st chromosome. The over-expression of SOD increases production of hydrogen peroxide [see SDN v4n10].
The latter fatty acid, DHA, is found in relatively high levels in human breast milk, but not in soy or cow's milk. Infant formulas manufactured in the US do not contain DHA, but many in other parts of the world do. The lack of DHA in early infancy, and/or its peroxidation, may have deleterious effects on cognitive development. The higher-than-normal incidence of nursing difficulties in DS infants may make them more at risk from this problem.
Piracetam mitigates oxidative stress and fluidizes brain membranes. The membrane fluidizing effects of piracetam have been reported in both rodents and man. The age-related decrease in brain fluidity seen in aged rats is partially corrected by administration of piracetam. However, in young rats, piracetam caused no measurable fluidization [Mueller et al., 1997]. This suggests that piracetam has a normalizing or self-limiting effect on brain membrane fluidity. In other words, if fluidity is normal, nothing happens, if fluidity is abnormal, it is normalized. This finding may be of particular interest in DS due to the possibility of abnormal fluidity changes in early infancy and childhood. Although this has yet to be measured directly, various signs of decreased membrane fluidity are evident (seizure risks are high in infants, and they have been observed to increase over time).
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