Let's put it all together. The brain contains neurons that never divide, and astrocytes and microglia, which can. Those that cannot divide are vulnerable to accumulated lifetime damage from free radicals and lipid peroxidation. The DNA damage that is not repaired prevents cells from performing normal functions and the neuron suffers from impaired energy production, decreased membrane repair, and damaged neurotransmitter production.
Numerous conditions can activate the brain's special immune system, including excess iron, glutamate, certain cytokines, lipid-peroxidation products, mercury, oxidized LDL and HDL, and beta amyloid.467 This means that as we grow older, our immune systems begin to attack our own brains.
Protecting the brain requires that we address all of these factors. For example, we know that the brain contains its own LDL- and HDL-type lipoproteins, just like those found in the blood. They become harmful only when oxidized, and can then promote excitotoxicity, free-radical production, and microglial activation.468 Flavonoids, especially epicatechin, have been found to prevent oxidation of LDL and HDL in the brain. Epicatechin is found in grape seed extract as well as green and white tea, which may explain in part why their consumption improves cognitive ability.469
Hormones also play a vital role in preserving our brains. As we age, DHEA—an adrenal hormone precursor for production of the reproductive hormones estrogen and testosterone— levels begin to fall. Interestingly, the brain contains receptors for DHEA, and several studies have shown that these receptors are capable of protecting the brain against damage.470
Depression is a major problem in the elderly and DHEA may be able to help. One recent study found that when DHEA was given to elderly patients with major depression, all but one improved significantly.471 The big surprise was that memory also improved significantly. The one patient that did not respond continued on the DHEA, and after six months her depression rating improved 48-72 percent and her semantic memory improved 63 percent.
The brain also contains receptors for pregnenolone. This adrenal hormone, which is a precursor of DHEA and other steroid hormones, also protects brain cells.472 Pregnenolone also declines with aging, showing a 60 percent reduction by age seventy-five. It has many interesting properties, several of which may make it useful in protecting the brain and improving brain function. For example, it has powerful anti-inflammatory properties, which may protect against Alzheimer's disease.473
One advantage of pregnenolone supplementation may be its ability to restore glutamate receptors in the brain, which are commonly lost with aging. While excess glutamate acts as an excitotoxin, the receptors are necessary for memory storage.
Several ongoing studies are investigating pregnenolone's efficacy, and early results are conflicting. In one, significant behavioral complications were seen. In a more recent study using larger doses of pregnenolone, improvement was seen.474 The reason I generally do not recommend pregnenolone supplementation, except in special situations, is that it can induce seizures in seizure-prone individuals, cause damage to the retina in cases of eye diseases and increases excitotoxicity. Because it reduces activation of the AMPA type glutamate receptor, one thought to cause the damage in MS, it may be of use in this condition. More research is needed before it can be recommended for general use. More research is needed before it can be recommended for general use.
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