The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 5 • September 2015


THE CHOLINERGIC NERVOUS SYSTEM IN THE BRAIN

Memory and Learning, Sexual Desire (LIBIDO), Reduction of Pain

Galantamine Enhances Cognitive Performance in Aged Ovariectomized Rats

One of the best ways to protect your aging brain is to get adequate amounts of choline, either through the diet (eggs, liver) or via supplements. As we have pointed out before, some 92% of Americans do not get even the minimal amount of choline recommended by the U. S. Institute of Medicine in their diet. Moreover, older women (past menopause, hence, with lower levels of estrogen in their system) require even more choline than premenopausal women. (Fischer, 2010) A food industry trade publication called this “Choline: The Silent Deficiency” and pointed to an opportunity for food companies to find ways to fortify their food products with choline. (See the January 2015 issue of “Prepared Foods.”)

As we have also reported before, cholinergic nervous system activity in the brain is vitally important for, among other things, cognitive performance. In women, it has been found that estrogen enhances the effects of cholinergic activity in the brain involved in learning and memory. With age in humans, the ability of the brain to take up choline declines. (Cohen, 1995)

Galantamine is a cholinesterase inhibitor, a class of compounds (in the case of galantamine, this is a natural substance despite being offered in a prescription form) that increases the length of time that the signal for cholinergic nervous system activation remains turned on in the neuronal synapse. Mounting evidence indicates that estrogen enhances brain function in women by increasing cholinergic nervous system activation. For example, a recent paper (Dohanich, 1989; reviewed in our last newsletter) showed that in rodents androgen-inhibited estrogen induced sexual receptiveness (LIBIDO) was prevented by choline, indicating that estrogen acted via a cholinergic mechanism to prevent androgen inhibition of libido or, another way of putting it, androgens had an anticholinergic effect in the female brain thus inhibiting libido induced by estrogens.

A recent paper (Gibbs, 2011) shows that galantamine plus estradiol enhanced cognitive performance in aged female rats with reduced levels of estrogens (as compared to young female rats). (This paper was previously reviewed by Will Block in the Dec. 2012 issue of Life Enhancement.) Especially interesting here was the fact that galantamine was able to enhance the effects of estradiol in the acquisition of a cognitive task (called the DMP, delayed matching to position, task—see paper for details of this, for a rat, fairly complex task) even after an extended period of reduced estrogen levels following ovariectomy. The rats were ovariectomized at 16-17 months of age. At 21-22 months of age, rats received daily galantamine treatment or vehicle by subcutaneous injection, then after a week, half the rats also received estradiol subcutaneously. Interestingly, neither galantamine nor estradiol alone had any effect on the rats after this extended period following ovariectomy.

Nevertheless, the COMBINATION of galantamine and estradiol significantly improved the animals’ ability to perform the DMP task, but not a different cognitive task, the stimulus discrimination/reversal learning task. Still, this is a very impressive enhancement of cognition in female rats after an extended period of very low estrogen in the brain and systemically. The authors suggest that this might indicate that “older women who have not used hormone therapy for many years and are beginning to show signs of mild cognitive impairment” could benefit from such a regimen. This is indeed good news for older women who have previously passed on hormone replacement because of concerns about it and are reaching the point where cognitive decline is becoming noticeable.

References

  • Dohanich and Cada. Reversal of androgen inhibition of estrogen-activated sexual behavior by cholinergic agents. Horm Behav. 23:503-13 (1989).
  • Cohen, Renshaw, Stoll, Wurtman, et al. Decreased brain choline uptake in older adults. JAMA. 274(11):902-7 (1995).
  • Gibbs, Chipman, et al. Galanthamine plus estradiol treatment enhances cognitive performance in aged ovariectomixed rats. Horm Behav. 60:607-16 (2011).
  • Fischer, da Costa, et al. Dietary choline requirements of women: effects of estrogen and genetic variation. Am J Clin Nutr. 92:1113-9 (2010).

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