01 May 2000
A WELL-FUNCTIONING MIND
A well-functioning mind develops out of an intricate interplay between biology and experience. An infant endowed with all the neurons in the universe won’t develop a good mind unless those neurons are linked up and enlarged through an active exploration of the environment.
For adults, the same "use it or lose it" idea applies. Within the last two years, researchers have found evidence not only that the human brain continues to generate new brain cells into old age, but that the survival rate of those cells can be increased dramatically through programs of physical and mental exercise.
On the other hand, what about when an infant gets to be an octogenarian and begins to lose carefully-nurtured brain cells, and the memories housed in them, to Alzheimer’s? Then it’s biology, not experience, that fails. This is the level at which futuristic technologies such as fetal tissue, stem cell, and nerve growth factor implants operate.
Stem cells are "generalist" cells that can divide without limit and produce specialized cells of the brain and body, including brain cells. When a human egg is first fertilized by a sperm, it becomes a single cell from which all cells of the body-to-be will be created. This "mother of all stem cells" is what biologists call totipotent, meaning that it has unlimited creative capacity. One level down from the totipotent "mother" stem cell are pluripotent cells, capable of generating all the cells of the body but not the placenta that the fetus needs to survive. By a process of division and specialization, further levels of stem cells are created, leading ultimately to each particular cell — blood, brain, skin, etc. — of the body.
Some of the more specialized stem cells continue to exist in your body after you’re born — indeed, all your life. Blood stem cells, for example, generate new red blood cells, white blood cells, and platelets ad infinitum. They can’t generate all the cells types in your body — they aren’t totipotent or pluripotent — but they’re still multipotent, capable of generating a number of different specific cells of a general type.
Until very recently, the accepted wisdom has been that we carry no stem cells for the brain into adulthood — that, in other words, central nervous system cells in the brain and spine can’t regenerate the way that the cells in our skin, blood, and other body systems do. As with so much other long-accepted knowledge about the brain, this turns out to be wrong.
There’s a chemical called bromodoxyuredine (BrdU) which is used as a kind of marker to pinpoint rapid cell division, as happens most dramatically when healthy cells turn cancerous. In 1998, the Salk Institute’s Fred Gage performed autopsies on several terminal cancer patients who’d been injected with the chemical, and found BrdU in their brains — evidence of recently-created brain cells. Other studies since then have shown the ongoing regeneration of neurons — neurogenesis — in the brains of adult animals, including primates closely related to humans. University of California-San Francisco researchers Daniel Lowenstein and Frank Sharp have recently found evidence for adult human neurogenesis after a trauma such as an epileptic seizure or a stroke. So it turns out that there are indeed brain stem cells that we carry with us all our lives.
One of the most controversial aspects of stem cell research has to do with the harvesting of pluripotent stem cells from aborted human fetuses. The hope is that such cells may be coaxed into generating any of a number of kinds of more specialized cells, and then implanted into the body or brain of a person with a disease of a corresponding cell or organ type, such as diabetes (pancreatic cells), heart disease (heart cells), or Parkinson’s or Alzheimer’s (brain cells). This "coaxing" is a matter of switching on the right genes in the stem cell that result in development into just the right kind of more specialized cell. Recent evidence indicates that this may be accomplished by identifying the appropriate growth factor — a kind of brain cell nutrient — that spurs the cell in the desired direction.
A somewhat simpler technique would be to extract fetal tissue that has already become specialized in the right direction. This has in fact already been successfully done by a Swedish team led by Anders Bjorklund, who implanted fetal brain cells into the brains of Parkinson’s patients.
It’s important to remember, though, that your brain has its own self-support and regeneration mechanisms which may be activated by physical and mental exercise. Physical exercise raises levels of the growth factor BDNF, for example, and growth factors in turn help to maintain healthy brain cells and protect them from neuron-destroying molecules such as free radicals. A mechanism such as this may be at play in the studies that indicate a self-challenging lifestyle may have a preventive effect against Alzheimer’s.
In addition, for genetically-determined brain diseases such as Huntington’s (the neurodegenerative disorder that felled Woody Guthrie), animal studies show that the course of progression of the disease — at what age the symptoms appear, and how severe they are — can be strongly improved by living in an interesting and mentally challenging environment.
And even with a procedure as invasive as fetal implants, the "use it or lose it" doctrine still applies — just as it does to newborns. Many researchers (prominently including David Swaab, one of the foremost proponents of the application of the "use it or lose it" concept to the brain) believe that a crucial factor in the survival of implanted stem cells is the degree to which the recipient uses those new cells for the purpose for which they’re implanted in the first place. A 1995 animal study showed that the success of hippocampal brain implants (the hippocampus is a seat of learning and memory in the brain) may hinge on "postoperative housing" — simply put, the number of interesting and challenging toys in the mouse’s cage.
So we shouldn’t let the promise of futuristic brain technology lure us into a state of complacence about the state of our minds. Ultimately, only the owner of a brain can save it from the consequences of an ossified existence.
|
