Rejuvenation

Rejuvenation

At the beginning of the twentieth century the world's most outstanding neuroanatomist, Nobel Prize winner Santiago Ramon y Cajal, who laid the groundwork for our understanding of how neurons are structured, turned his attention to one of the most vexing problems of human brain anatomy. Unlike the brains of simpler animals, such as lizards, the human brain seemed unable to regenerate itself after an injury. This helplessness is not typical of all human organs. Our skin, when cut, can heal itself, by producing new skin cells; our fractured bones can mend themselves; lost blood can replenish itself because cells in our marrow can become red or white blood cells.

But our brains seemed to be a disturbing exception. It was known that millions of neurons die as we age. Whereas other organs make new tissues from stem cells, none could be found in the brain. The main explanation for the absence was that the human brain, as it evolved, must have become so complex and specialized that it lost the power to produce replacement cells. Besides, scientists asked, how could a new neuron enter a complex, existing neuronal network and create a thousand synaptic connections without causing chaos in that network? The human brain was assumed to be a closed system.Ramon y Cajal devoted the later part of his career to searching for any sign that either the brain or spinal cord could change, regenerate, or reorganize its structure. He failed.

In his 1913 masterpiece, Degeneration and Regeneration of the Nervous system, he wrote, “ In adult brain centers the nerve paths are something fixed, ended, immutable. Everything may die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree.”

There matters stood.

The neuronal stem cells I see are vibrating with life. They are called “neuronal” stem cells because they can divide and differentiate to become neurons or glial cells, which support neurons in the brain. The ones I am looking at have yet to differentiate into either neurons or glia and have yet to “specialize,” so they all look identical. Yet what stem cells lack in personality, they make up for in mortality. For stem cells don't have to specialize but can continue to divide, producing exact replicas of themselves, and they can go on doing this endlessly without any signs of aging. For this reason stem cells are often described as the eternally young, baby cells of the brain. This rejuvenating process is called “neurogenesis,” and it goes on until the day that we die.

Paradoxically, sometimes losing neurons can improve brain function, as happens in the massive “pruning back” that occurs during adolescence when synaptic connections and neurons that have not been extensively used die off, in perhaps the most dramatic case of use it or lose it. Illustration by Elena.

Neuronal stem cells were long overlooked, in part, because they went against the theory that the brain was like a complex machine or computer, and machines don't grow new parts. When, in 1965, Joseph Altman and Gopal D. Das of the Massachusetts Institute of Technology discovered them in rats, their work was disbelieved.

Then in the 1980s Fernando Nottebohm, a bird specialist, was struck by the fact that songbirds sing new sons each season. He examined their brains and found that every year, during the season when the birds do the most singing, they grow new brain cells in the area of the brain re responsible for song learning. Inspired by Nottebohm's discovery, scientists began examining animals that were more like human beings. Elizabeth Gould of Princeton University was the first to discover neuronal stem cells in primates. Next, Eriksson and Gage found an ingenious way to stain brain cells with a marker, called BrdU, that gets taken into neurons only at the moment they are created and that lights up under the microscope. Erikson and Gage asked terminally ill patients for permission to inject them with the marker. When these patients died, Erikson and Gage examined their brains and found new, recently formed baby neurons in their hippocampi. Thus we learned from these dying patients that living neurons form in us until the very end of our lives.

The search continues for neuronal stem cells in other parts of the human brain. So far they've also been found active in the olfactory bulb (a processing area for smell) and dormant and inactive in the septum (which processes emotion), the striatum (which processes movement), and the spinal cord. Gage and others are working on treatments that might activate dormant stem cells with drugs and be useful if an area where they are dormant suffers damage. They are trying to find out whether stem cells can be transplanted into injured brain areas, or even induced to move to those areas.

To find out if neurogenesis can strengthen mental capacity, Gage's team has set out to understand how to increase the production of neuronal stem cells. Gage's colleague Gerd Kempermann raised aging mice in enriched environments, filled with mice toys such as balls, tubes, and running wheels, for only forty-five days. When Kempermann sacrificed the mice and examined their brains, he found they had a 15 percent increase in the volume of their hippocampi and forty thousand new neurons, also a 15 percent increase, compared with mice raised in standard cages.

Mice live to about two years. When the team tested older mice raised in the enriched environment for ten months in the second half of their lives, there was a fivefold increase in the number of neurons in the hippocampus. These mice were better at tests of learning, exploration, movement, and other measures of mouse intelligence than those raised in unenriched conditions. They developed new neurons, though not quite as quickly as younger mice, proving that long-term enrichment had an immense effect on prompting neurogenesis in an aging brain.

(Rejuvenation. The Brain That Changes Itself by Norman Doidge, M.D., excerpt).

Keeping unused neurons supplied with blood, oxygen, and energy is wasteful, and getting rid of them keeps the brain more focused and efficient. Illustration by Elena.