Neurons wire and change constantly

How the brain copes with age and alcohol.

It is a biological truism that nerve cells cannot divide like other cells in the body and thus form anew. When a person is born with 100 billion brain cells and tackles the joys and sorrows of earthly life, he has an initial capital that he can only keep or lose in quantitative terms. Studies on the brains of deceased people have shown that brain mass shrinks as they get older: Between twenty and seventy people lose 200 to 300 grams of brain matter; a ninety-year-old still has two thirds of his original brain weighing one and a half kilograms. The early brain researchers saw in this loss of substance the explanation for the observed reductions in brain performance in old age and soon had impressive figures for the creeping decay at hand: throughout life, between 10,000 and 100,000 neurons (nerve cells in the brain) passed every day. broken. And those who have a penchant for alcohol, it was said, wash a similar number again into ruin.

As terrible as such numbers may seem, if you extrapolate them, even after a long and at best slightly boozy life, well over 90 billion of the 100 billion neurons remain. The message becomes even more comforting if one takes note of the research results of the last decades, according to which the number of neurons remains largely constant throughout life and only decreases noticeably in certain areas of the brain. The lightening of the brain is primarily the result of the loss of supporting cells (they form the framework for the nerve cells) and the shrinking of large neurons; In addition, the number of connections between the individual nerve cells is reduced. The organism therefore carefully ensures that its command center is maintained. And as we now see, the formation of the brain is already much more sophisticated than the scholars imagined it would be earlier. The human embryo begins its brain development around the eighth week of pregnancy. He builds up the inventory of 100 billion nerve cells over the next four months - which means an ongoing production of over 500,000 neurons per minute. The newly created neurons still have to look for their future place of work in the brain - a migration that lasts approximately until birth.

This provision of the basic neural structure is strictly predetermined by the genetic blueprint, because nature does not want to afford any randomness here. The brain only becomes a supercomputer when its billions of building blocks are linked together and function as a gigantic communication network. Since every nerve cell is now coupled with the neighboring nerve cells via 1000 to 10,000 switching points (synapses), the result is an unimaginably complex data processing system with several hundred trillion connections. In computer jargon, no less than a thousand gigabits (one trillion bits) of information are stored in the brain, the equivalent of over 60 million typewriter pages.

If it used to be believed that the neurons were "wired" according to a fixed genetic blueprint and that the brain only began to work when its internal contacts were made, research over the past ten years has produced a completely different picture. The reason for doubt about the ready-made brain theory was the consideration that the genetic database stored in the tiny cell nucleus of the egg cell and the sperm cell could not store the detailed instructions for establishing the myriad neural contacts in addition to the blueprint for the entire organism. So how does the brain find its function?

From around the middle of pregnancy, the axons, the long main branches of the nerve cells that are responsible for long-distance contact (e.g. from the retina of the eye to the visual center on the cerebral cortex), begin to form numerous side branches. These side branches connect rather randomly with the side branches of other nerve cells. The resulting network is a mess for the time being; it only finds its meaningful structure through the real world. In the first years of life, the nerve cells strengthen the contact pathways that are activated by external stimuli - for example on the retina or the skin of the body. And they break off nerve connections for which there is obviously no need. In this way, the brain gradually comes to a structure that is decisively shaped by the specific environment. The view that a toddler should be interested in the outside world with play and care is therefore of fundamental importance for brain development. What a deficit can mean here is shown by the example of children who are born with severe lens opacification. If this error is not diagnosed soon after birth and the defective lens of the eye is corrected, the brain foregoes the nerve connections in question due to the lack of light stimuli - the eye becomes and remains blind forever.

This plastic adaptation of the young brain is also proven by studies on mammals and birds. In young cats, for example, it was possible to study how the visual cells in the eye determine their target area on the visual cortex in the back of the brain only through active vision. The axons and synapses of the nerves are remodeled on a large scale until light stimuli that strike next to each other on the retina also stimulate neighboring areas on the visual cortex and thus create an image of the outside world in the brain. So that the animal already has a head start in this neural learning at the time of birth, bursts of ordered nervous action patterns arise spontaneously on the retina in the darkness of the uterus. How far this kind of brain adaptation can go is known from songbirds. Both the young males and the females have neuronal structures in the forebrain that enable them to sing. After sexual maturity, however, only the males sing, which is why the females unceremoniously break down the entire singing center in the brain.

Another surprise of modern brain research is that the early development of the human brain, depending on the brain region, lets a greater or lesser number of its neurons die again “on purpose”. The breakdown takes place where the individual brain experience shows that the number of nerve cells ending in a certain target area is too large for the specific task. Because the brain, with its necessarily high energy consumption, cannot afford useless eaters.

Neural adaptation to the real world lasts well beyond childhood. The autopsy of people of different ages has shown that the density of the switching points (for example in the frontal lobe) decreases significantly in adolescence. Presumably this is part of the brain's strategy to steer the childish way of thinking, which is often still overflowing, into more stable channels. The pathological inability to sort emerging associations and to spin a thread of thought to the end is the hallmark of schizophrenia. Could a lack of useful tightening of neuronal activity in the adolescent brain be the still puzzling cause of schizophrenia? The fact that this mental illness usually breaks out in later childhood speaks in favor of this possibility.

One of the most exciting discoveries is the realization that the human brain adapts itself to its sensory impressions and thought processes throughout its life, i.e. constantly readjusts itself. Certain synapses are strengthened through learning and thus memory contents are strengthened neuronally. It has been shown in monkeys that targeted training of certain fingers can enlarge their target area on the cerebral cortex even in adulthood at the expense of neighboring sensory addresses. This flexibility is especially useful as you get older. Since nerve cells cannot form new, damage caused by external toxins and their own metabolic products accumulates. The poor blood circulation in old age also increases the damage to the neurons.

Many of the nerve processes atrophy. The transfer of information at the synapses with the help of chemical messengers is also becoming increasingly inefficient. This is why thinking begins to slow down between the ages of fifty and sixty, new situations are less quickly understood, and short-term memory suffers. However, if you give the older person time, they can still solve the puzzle. And professional and professional, as they grow older, usually manage to make up for the greater intellectual agility of the younger generation thanks to longer life experience, accumulated specialist knowledge and psychological balance.

The brain also anatomically defends itself against the deficits of old age. The hippocampus is part of the limbic system, an area of ​​the brain mantle that is important for learning processes, memories and emotions. In the hippocampus, around 5 percent of neurons disappear with every decade of the second half of life - around 20 percent in total by the end of life. The nerve cells in the hippocampus of people of different ages have been examined after death and an astonishing discovery has been made: if one measures the mean length of the nerve cell processes, there is significant growth between the fifth and eighth decade of life. Only in old age do the appendages become shorter again. This late nerve growth could very well mean the efforts of particularly efficient nerve cells to compensate for the age-related loss of neighboring cells.

The fact that the brain can withstand the ravages of time is shown by those spirits whose creativity was retained into old age: Simone de Beauvoir wrote “The Farewell Ceremony” at the age of 75; At the age of 81, Marc Chagall furnished the Fraumünster in Zurich with stained glass; Otto Klemperer conducted the London New Philharmonia Orchestra at the age of 85; At 92, Frank Lloyd Wright was in charge of building the Guggenheim Museum in New York; George Bernhard Shaw wrote over 90 plays, and Bertrand Russell wrote "The Art of Philosophizing" at 96. Artur Rubinstein, who still gave piano concertos at 89, revealed how clever tactics can counter age-related restrictions: he overcomes the weaknesses of old age by practicing more, deliberately limiting his repertoire - and slowing down before fast passages so that the fast part appears to be played more nimbly than is actually the case.

Brain researchers and psychiatrists today agree: In healthy old people, the brain function is not significantly restricted. However, if the brain is exposed to toxins for a long time, pathological changes occur. In two thirds of chronic alcoholics, for example, an X-ray shows a shrinkage of the brain. According to recent studies, brain changes can already occur with a continuous consumption of 40 grams of alcohol per day - a dose that already contains half a liter of wine. This brain breakdown mainly affects the white matter of the cerebrum (it consists mainly of supporting cells and the appendages of the nerve cells), while the gray cerebral cortex (the thinking center packed with nerve cells) is spared from breakdown.

This was recently confirmed by a Danish study that compared eleven brains of deceased heavy alcoholics with eleven brains of deceased non-drinkers. The total number of nerve cells in the cerebral cortex, extrapolated from numerous tissue preparations, was 23 billion for both groups, and the weight loss of around ten percent found in the brains of long-term alcoholics only affected the white substance. Alcoholics therefore have the (meanwhile also medically confirmed) chance to regenerate the damaged brain tissue7 by means of abstinence. (For a destroyed liver, however, nature has no recourse.)

The connoisseur of a good drop of wine may be pleased with the message from the Bordeaux University Hospital: As studies on 4,000 people over 65 years have shown, a quarter of a liter of wine per day reduces the aging process of the brain by more than a third. So the brain can cope with moderate amounts of alcohol. With one exception: in its early development, even a single boozy evening can be devastating. Alcohol embryopathy is the most common developmental disorder in newborns. The sad consequences of alcohol consumption during pregnancy range from learning disabilities and behavioral disorders to short stature and severe motor or mental disabilities.

The brain can degrade unusually early and quickly and destroy a large number of neurons, pathological processes with as yet unknown cause. In Parkinson's disease, "paralysis", more and more brain cells disintegrate in the substantia nigra. Since the affected region produces the chemical messenger substance dopamine, which is important for the transmission of signals for posture and movement, the clinical picture deteriorates from initial pain in muscles and joints to stiffness, partial rigidity and trembling of the head, hands and feet . Finally the patient shuffles through life with small steps, his voice low and monotonous. If the symptoms initially only affect the motor skills, most Parkinson's patients also develop intellectual deficits later on. And while drugs can be used to replace the missing dopamine and thus greatly reduce motor disorders, unfortunately dementia cannot yet be remedied.

By far the largest proportion of senile dementia is due to Alzheimer's disease, a condition characterized by a rapid deterioration in memory, thinking and judgment. Symptoms like those that can also occur in old age due to normal mental decline. However, Alzheimer's disease often begins between forty and fifty and runs through the scale of progressively worsening mental disorders at the rapid pace of a few years. As with Parkinson's, the cause of Alzheimer's disease is unknown. One can only observe the damage that has occurred in the brain post mortem: unusually frequent deposits of the protein beta-amyloid (a waste product of the brain metabolism that occurs in small amounts in the healthy brain) and chaotic tangles of neurofibrils, the supporting structures inside the nerve cells.

Such organic brain disturbances put a growing number of neurons out of action - a mental bloodletting that the brain is soon no longer able to compensate despite its repair possibilities. There are currently 150,000 Alzheimer's patients in Switzerland; This brain disease is already responsible for 60 percent of all senile dementias. And the rapidly increasing number of elderly people will continue to increase the number of Alzheimer's patients. In addition, with a share of 20 to 30 percent of all senile dementias, there are multiple minor strokes. They are the result of vascular calcifications, whereby the disturbed blood flow can atrophy whole areas of the brain. For 2020, 1.6 million people in Switzerland are expected to be of retirement age. Almost 7 percent of them will have brain disorders and will therefore more or less require care. In the over eighty-year-olds, 20 percent of demented patients must be expected. On the other hand, this also means that four fifths of the very old can still use their brains reasonably well.

There is currently a global race in pharmaceutical research to find drugs against Alzheimer's disease and other brain disorders. It has been known for some time that nerve growth substances protect brain cells from damage and promote their regeneration. These growth substances also have a special effect on the nerve cells in the hippocampus, which is particularly badly affected by Alzheimer's disease. It is hoped that biotechnologically produced growth substances will be able to influence the disease favorably in the future. A much larger pharmaceutical market than the brain-sick are those people who fear for their brain performance as they get older and want to cure even minor losses. The "organic brain psychosyndrome" (HOPS) as a hodgepodge for sleep disorders, dizziness, premature fatigue, irritability and concentration disorders has become a fashionable term for many doctors in recent years. Accordingly, there are numerous preparations on the market that claim to help the tired brain get going again. As “vasodilators” they are supposed to widen the blood vessels and thus better supply the brain with blood; as «nootropics» literally «straighten the mind», that is, have a beneficial effect on memory, language and ability to concentrate. In addition to increased blood circulation, improvements in energy metabolism and synapse function should also contribute to increasing performance.

How important such hopefuls have become is shown by their sales: extracts from the leaves of the Asian ginkgo tree are in the first place of all medicines sold in Germany. The ginkgo ingredients are said to improve the blood flow to the brain and thus help with poor concentration and dizziness. Hydergin, made from various alkaloids of ergot, has also been in the forefront of the pharmaceutical hit parade for over forty years.Originally composed by the LSD discoverer Albert Hofmann at Sandoz as a blood pressure lowering drug, the drug has become a classic among the nootropics. Countless pharmacological and clinical studies have shown that the drug corrects age-related disturbances in signal transmission in the brain and thus improves memory, balance, sleep and alertness.

The sales of vasodilators and nootropics are impressive: 33 million Swiss francs in 1992 in Switzerland and 2.2 billion dollars in the USA. In spite of such public success, many experts view the means with great skepticism. Because all the effects that have been proven so far are at most marginal and the improvements in blood circulation and oxygen and sugar consumption measured in the brain are only short-lived. The funds would also be of practically no use where they were most needed - in the long-term therapy of senile dementia. Albert Wettstein, chief physician of the Zurich City Medical Service, said about the extensive range of vasodilators and nootropics that deterioration had never been observed after they were discontinued in new patients - on the contrary. Stopping certain medications, especially sedatives, which the patient has been prescribed for a long time, often brings spectacular improvements and in many cases shows that "senile dementia" only apparently existed.

The Federal Social Insurance Office in Bern has drawn the corresponding conclusions. Whereas in 1977 there were 46 “vasodilators” on the list of drugs eligible for reimbursement, in 1993 there were only 15 products under “vasodilators and cerebral activators”, which together contain only half a dozen different types of active ingredients.

As unconvincing as the successes of pharmacological aids for the aging brain have been so far, the industry is by no means discouraged. In addition to multivitamins as a non-specific fuel additive for body and mind and other revelations from “God's Pharmacy”, the wave of “smart drugs” is now rolling towards humanity. With “Cognex”, the first “cognition enhancer” came onto the market in the USA a few months ago, a chemical preparation that is supposed to markedly improve memory and attention. For the time being approved for the treatment of Alzheimer's patients, the new preparation is aimed at the much larger market of people with “Age-Associated Memory Impairment”, as the decline in memory performance in the course of normal aging is defined as a new “disease”. Ultimately, millions of schoolchildren and professionals who want to increase their mental efficiency should also benefit from the modern mental aids. According to a pharmacological journal, at least 180 such memory pills are currently being developed around the world.

Those scientists who want to tackle brain problems with a knife have even more radical ideas in mind. In the 1980s, the United States and Sweden began to implant dopamine-producing cells in Parkinson's patients from their own adrenal medulla or from the brain tissue of embryos. Transplant attempts with brain cells have also been made in schizophrenics; future candidates are patients with neurological disorders such as Alzheimer's disease, epilepsy and brain injuries. The initial enthusiasm for the first favorable results has now been followed by disillusionment. The surgical replacement of diseased brain tissue seems much more difficult than originally assumed. Because the functioning of the brain is not only a question of the individual nerve cells, but above all the mutual wiring of the neurons. However, this is the result of lifelong personal development and cannot be replaced by a transplant.

In his book «Hirnverpflanzung», the neurosurgeon Detlef Linke from Bonn poses even more fundamental questions: Isn't the surgical exchange of brain tissue an intervention in the ego? Doesn't foreign brain matter ultimately change individuality and soul? No medical progress will be able to change the fact that with the demise of the old brain the original personality is inevitably also lost.

Herbert Cerutti is the science editor for the NZZ.

This article comes from the NZZ Folio magazine from March 1994 on the subject of "In the brain". You can order this issue or subscribe to the NZZ Folio.