When Gash sacrificed the rats and examined the grafts, he found that the control of water consumption had occurred only when the fetal cells had been grafted at the site where vasopressin-producing cells occur in healthy rats, and thus where there are receptors for the hormone they produce. These studies showed that precise placement of the graft within the recipient's brain is crucial to success.
Neurobiologists Earl A. Zimmerman of the Oregon Health Sciences University and Ann-Judith Silverman of Columbia University have performed similar work with rats whose brains do not produce a hormone called GnRH and whose reproductive organs therefore do not develop.
After Zimmerman's group transplanted GnRH-producing fetal brain cells from healthy rodents into males, Zimmerman said, the rats' testicles grew and they began producing sperm.
Ten GnRH-deficient female rats received similar transplants, Silverman said, and their ovaries and uteruses grew to normal size. "All 10 mated, and six gave birth to healthy litters."
A key point, Zimmerman noted, was that the scientists obtained "a total response in the females with only 20 to 25 cells." A normal rat brain has more than 200 GnRH-producing cells.
The fact that so few transplanted cells can produce an effective response suggests that a small number of healthy cells also can make a major improvement in diseases such as Parkinson's.
The majority of scientists studying brain grafts are working with animal models of human diseases that are more widespread, particularly Parkinson's disease and Alzheimer's disease. If the symptoms of these diseases can be cured by grafts in animals, then the prospects are good that the grafts may work similarly in humans.
Affects 1 Million
Parkinson's disease, which affects more than 1 million Americans, mostly over age 50, is characterized by difficulties in movement, body rigidity and tremors. As many as 30% of the victims also develop dementia--a severe loss of mental powers.
The disease is caused by the death of brain cells that produce the hormone dopamine. It can be controlled, at least in the early stages, by use of the drug L-dopa, which increases the brain's dopamine supply. As the disease becomes more severe, however, patients receive less benefit from the drug.
Parkinson-like symptoms can be induced in rats by injecting dopamine-producing cells with the toxic chemical 6-hydroxydopamine. If the chemical is injected into cells on the left side of the brain, it will kill cells controlling the right side of the body and the rats will walk in clockwise circles. If it is injected into the right side of the brain, the rats circle in a counterclockwise direction.
Neurobiologist William J. Freed and his colleagues at the National Institutes of Mental Health, working with Olson and Bjorklund, have shown that it is possible to correct this circling behavior by grafting dopamine-producing fetal brain cells into the brains of the damaged rats.
Similar results were also obtained, according to Freed, when they transplanted cells from the rats' own adrenal glands into the damaged brains. Although the glands normally produce dopamine, the chemical cannot reach the brain because of the "blood-brain barrier," which prevents most chemicals in the blood from reaching the brain.
Alzheimer's is a more complex disease whose cause is not yet known, but whose primary symptom is dementia. It affects as many as 2.5 million Americans, mostly over age 65.
The disease is characterized by below-normal concentrations of several brain hormones, including dopamine, norepinephrine, and acetylcholine. Some of the symptoms of Alzheimer's, such as failing memory and loss of agility, occur naturally during aging or can be produced artificially in animals, and there is evidence that these symptoms can be improved by transplants.
Neurobiologist John R. Sladek Jr. of the University of Rochester, working with Gash, has identified a group of rats that exhibit an age-related decline in norepinephrine production that is accompanied by certain behavioral changes. In particular, the rats have difficulty learning to avoid an electrical shock and they will not eat new foods.
Sladek said that grafting norepinephrine-releasing brain cells from fetuses into the old rats produced a "marked improvement" in their ability to learn to avoid shocks and also increased their acceptance of new foods. In contrast, grafting of brain cells that did not release norepinephrine produced no effect.
Bjorklund and Olson have similarly found that transplanted fetal cells can restore acrobatic activity in old rats. As tests of agility, the rats were required, for example, to walk along narrow rods.