Loss of critical hormones linked to failing memory MAINTAINING THE BRAIN

October 04, 1994|By Ronald Kotulak | Ronald Kotulak,Chicago Tribune

After decades of helplessly watching Alzheimer's, Huntington's and other diseases ravage the brain, medical science is striking back with a potent weapon -- the brain's newly discovered power to heal itself.

Enlightened by the insights of molecular biology, scientists now know that Mother Nature equips the brain with a kind of fountain of youth -- hormones and other chemicals that nurture and

sustain brain cells. But when the fountain begins to dry up, as it sometimes does with age and some mental disorders, brain cells wither and die.

Memory loss, Alzheimer's, Parkinson's, Huntington's and other degenerative diseases are now believed to be the biological desert created when these rejuvenating chemicals vanish. If we can measure when our brain-nurturing chemicals start to decline and restore them to youthful levels, we may be able to cure or prevent many of the things that go wrong with the brain.

Hormones -- estrogen, progesterone, testosterone and growth hormone -- play key roles in maintaining many types of brain cells, researchers now believe. Some of these hormones, which may become the first effective drugs to prevent Alzheimer's disease and memory loss, already have produced promising preliminary results.

"We have to think of the brain in terms of a system in balance," said neurobiochemist Dr. Eugene Roberts of the City of Hope's Beckman Research Institute in Duarte, Calif.

"When a part of the system changes -- like a decline in estrogen, growth factors or other hormones -- the balance is upset and that's when the trouble starts," said Dr. Roberts, who has shown that he can improve memory in aging animals with a brain hormone called DHEA. Dr. Roberts is now testing the precursor of DHEA, a basic hormone called pregnenolone, in human beings to determine whether it improves their memories.

Fortunately, most brains work well throughout life, diminishing only slightly in memory power with age. For many who do forget easily, the problem may simply be a matter of disuse -- in effect, they allow their brains to rust.

For those who have more fundamental problems with their memories -- the chemical and electrical circuits that make people who they are -- researchers are learning which chemicals need to increased. One of their biggest surprises is the discovery that estrogen has an ability to nourish many types of crucial brain cells.

Estrogen was once thought to be solely a female sex hormone involved in reproduction. But the hormone, a small, almost indestructible molecule with a biological passport to enter most cells, is turning out to be an important rejuvenator of female and male brains.

"People, and this is true for most doctors, are not aware of the fact that the brain is a major target of estrogen," said cell biologist Dominique Toran-Allerand of Columbia University.

Because of estrogen's ability to carry all sorts of biological messages, it has played a dominant role throughout evolution as a communications superhighway between the brain and the rest of the body in most living things. That becomes most obvious in women just before menopause, usually around age 50, when the ovaries drastically decrease their production of estrogen.

AThe brain itself appears to suffer when estrogen levels drop; the risk of Alzheimer's disease, for instance, increases in women after menopause. According to some estimates, postmenopausal women have 5 to 10 percent more Alzheimer's than men, whose estrogen levels do not plummet as rapidly. Several studies suggest that women who take estrogen supplements after menopause can significantly reduce their risk of Alzheimer's.

The male brain also is bathed in estrogen, a component of the male sex hormone testosterone.

Columbia's Dr. Toran-Allerand recently showed that estrogen stimulates the production of nerve growth factor, which is essential for the survivability of many types of brain cells, especially those involved in learning and memory.

Brain-cell connections

Estrogen also increases the sprouting of connections between brain cells, which determine the brain's power to produce thoughts and learn new things. Animal studies in Bruce McEwen's neuroscience laboratory at Rockefeller University showed that by increasing estrogen, more of these connections were formed. When estrogen was reduced, connections broke off and retracted. Finally, estrogen prevents a decline in acetylcholine, the chemical messenger that orders new memories to be imprinted in various parts of the brain. Alzheimer's patients suffer increasingly severe losses of acetylcholine, which first robs them of their short-term memory and eventually of long-term memory.

"Whatever it is that makes women and men at risk for Alzheimer's disease, if the brain is deprived of a necessary molecule [estrogen], then it may make those neurons [brain cells] more vulnerable to the disease," Dr. Toran-Allerand said.

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