The Root of Thought (20 page)

In another study, astrocytes and neurons were cultured together in a dish. A mass amount of amyloid beta was added to the cells. Calcium waves started in astrocytes and they killed off the neurons. Amyloid beta is normally scavenged by astrocytes, but in such large amounts, astrocytes must think the neuron is dying and prematurely euthanizes it. The brain can’t have a dilapidated unfixable road. Astrocytes are all about cleaning up their neighborhoods.

The astrocyte, one of which can contact 10,000 neuronal synapses, increases up the evolutionary ladder in the cortex. They are the most
abundant cells in the human cortex; they are the only regenerative cells in the cortex; and they can communicate with each other in intricate calcium waves. They do not have time for loiterers.

In aging, it was thought that a loss of neurons was the result of our cognitive decline as we aged. After further review, neuronal number seems to remain the same as we age. However, there is a higher incidence of a phenomenon called “astrocyte reaction.” A protein, called glial fibrillary acidic protein, or more commonly referred to as GFAP, becomes expressed in astrocytes in response to trauma, aging, and disease in the brain. In 1972, researchers at Stanford and the VA hospital in Palo Alto, California separated the cells and looked for immunoreaction to specific proteins that wouldn’t work with neurons and found that GFAP was shown to be a marker for astrocytes. GFAP is abundant throughout the brain, including in the cortex, and is the marker that was used to demonstrate dividing astrocytes near the ventricles. Higher astrocyte reaction occurs in the substantia nigra in Parkinson’s, the hippocampus in Alzheimer’s, and the motor cortex in ALS—not to mention the cortex in general.

GFAP is also the protein in the cells that are multiplying and the root of cell regeneration in the brain, the same cells that constantly replenish the olfactory bulb and hippocampus. These are the same cells that multiply throughout our lives in the cortex and the only cells that are the root of cellular regeneration as we age—the astrocyte.

As it ages, the brain continually tries to regenerate its glial cells. We each have a constant turnover rate of astrocytes in our brain. That rate, over time, is unique to us. However, if that rate tapers off and astrocytes die more quickly than they are replenished, we develop a degenerative disease of the brain. As we reach our biological limits in our old age, astrocytes might multiply less robustly. This lack of an adequate turnover rate might be what leads to diseases such as Alzheimer’s Disease, Parkinson’s Disease, and ALS.

It is conceivable that the loss of smell at the beginning of degenerative diseases of the brain is an indicator of the cause of the disease being the inadequate turnover rate of glial cells.

The lift of the ban on astrocyte research is leading us in amazing new directions. Even in normal aged people without dementia, plaques, tangles, and Lewy Bodies can be seen in neurons in the analysis of their brains—not to the extent of a patient like Alzheimer’s Auguste Deter, but enough to know it is a natural aging process. If astrocytes scavenge these proteins, then it is possible a deficit in astrocyte scavenging is present in disease. Fewer and tired astrocytes would lead to toxic buildup of proteins and molecules released by neurons.

If Parkinson’s Disease persists, the patient begins to have cognitive decline and dementia similar to what happens to Alzheimer’s patients. In Alzheimer’s, the movement disorder eventually develops. In both diseases, the patients have buildups of major neuronal proteins. Dementia with Lewy Bodies is a disease that begins with Alzheimer’s-like dementia and then ends with Parkinson’s-like movement disorder. People with Alzheimer’s in reality have some Lewy Bodies, and people with Parkinson’s in reality have some plaques and tangles.

In Parkinson’s, it has also been shown that dopamine-expressing neurons are not the only neurons that degenerate; neurons that transmit glutamate and the transmitter GABA have also been implicated. In ALS, the main feature is a degeneration of upper motor neurons, which reach down through the brain stem. However, other areas are now known to degenerate. The same occurs with Alzheimer’s; the hippocampus and cortex are the point of attack, which results in memory loss, but these are not the only areas that degenerate.

In degenerative disease of the brain, though, it is obviously true that for some people it initially attacks their movement, for some the cortex, for some hippocampus, and so on. Because it is known that most degenerative diseases of the brain are related and eventually the entire brain will degenerate, instead of lumping all Alzheimer’s patients together, it might be more interesting to try and understand why one particular person might be vulnerable initially in the basal ganglia and why someone else might be vulnerable in the cortex.

In ALS, the most work has been pursued on glia because of the toxicity of glutamate, the transmitter released by neurons in the cortex, and the uptake and release of glutamate by astrocytes known due to intricate studies in the late 1980s and early 1990s. However, the focus on receptors and proteins and all things molecular might overlook a basic cellular problem: Glia just can’t replace themselves as fast as they used to.

The fact that patients notice an inability to smell before they have other symptoms is telling. The cells for this area usually constantly and healthily turn over in response to the elusive ever-changing molecules floating around in our environment. Astrocytes are the cells that replenish the area. What would change if something happened to our constant astrocytic turnover in our life? What if we work our minds like a muscle to keep the growth constant and robust, but then a tweak caused by the environment or a trigger in our bodies causes this turnover to slow down? Unlike Einstein’s abundant glia, producing more astrocytes than the normal person, we might have trouble thinking and we might have trouble remembering. The transmitters fired by the neurons as information comes in from the senses might not be quenched and processed by enough glia; then problems would likely arise in our mental processing. Our brain goes from a booming mining town to a ghost town when the gold runs out. And the roads in and out of town are grown over with tumbleweed. But the roads don’t cause everything to fall apart, nor does the tumbleweed. Something happened to the town, and only when we find out how to bring back the gold will the town boom again.

The evidence that suggests that glial cells can clean up the excess proteins that accumulate outside neurons might lend support to the neurocentric view that glial cells might just be support cells—the busboys cleaning up the plates after the neuron eats a steak. However, even if this is the case, it doesn’t excuse the lack of research performed on glial cells.

More likely, glial cells are like a highway construction crew out there trying to fix the road when it has many potholes. They have to clean their roads so that the information they have can be acted on when they tell a neuron to send long-distance information. When the normal rate of regeneration in glia falls below normal pace, it is like an epidemic of the Black Plague has hit glial city. The glial cells will become fewer in number, unable to maintain their neural roads and potholes will develop in the form of protein buildup. Eventually the neurons will begin to die and the brain becomes full of dead glial cells and bad roads—a wasteland.

Many recent studies try to make use of neural stem cells and neural precursor cells. This has proved unsuccessful, because if more neurons are added to the brain, even if they make more connections, they still won’t be able to perform properly. The glial control is not there, and they would aimlessly fire.

Injections and replacement therapy with mature astrocytes has not been attempted. Controlling astrocyte implants might serve to help us understand whether the glial cells are indeed the problem. When researchers can accurately determine the rate of astrocyte turnover in a person, then they can try to keep that rate consistent. This could block disease that resulted from astrocytes not being able to replenish adequately as we age.

Most tragic is when the cortex begins to whither. It shrinks in disease. The most numerous cell in the cortex is the astrocyte. In 1906, Alzheimer himself suggested the astrocyte as a possible cause of his disease. However, a suggestion like that was not taken seriously in 1906, the year Cajal was laying down the gauntlet at the Nobel Prize lectures.

Whether the cause of the diseases of the brain is neuronal or astrocytic in nature, studies on astrocytes are imperative. The astrocyte’s known ability of scavenging abundant neuronal proteins and transmitters indicates that astrocyte research would benefit patients if not the same, then maybe even more so than research with a blind neuronal focus. If some trigger that has caused inadequate astrocyte turnover is the cause, depleting the brain of astrocytes and then resulting in neuron death, studies on astrocytes is the only way to reveal a cure.

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Evolution has created who we are, not perfect, but simply the state we are as a species today. Some aspects of the brain—for instance, how it has folded inside the skull—and the areas of location for different functions seem completely haphazard. Little makes sense when you step back and look at it. However, it is beneficial that the brain stem is hidden at the base of the brain because we aren’t going to have time to ponder how we evolved if we don’t survive a head-on collision with a wall.

The brain stem is hidden deep in the base of the brain because it controls our vital functioning, such as breathing and heart rate. If you are going to commit suicide, it is best to aim for the back of your mouth instead of straight into the roof of your mouth. Otherwise, you will just blow off the front of your brain. You can lie there for a day and the paramedics might still find you alive.

Although other medical treatments from antiquity have been lost over time, we know that treatment for brain injuries likely existed as long as 10,000 years ago. Skulls with holes drilled into them (signs of trephaning) have been found as far back as the ancient Egyptians, in the ancient Incan culture as well. This surgery could also have been a cure for psychosis to relieve evil spirits, but the indications seem to be that the person might have sustained some traumatic insult.

This relief of pressure and swelling by cutting open a hole in the skull is still used by neurosurgeons today. Brain injuries come in two main types: open head injury and closed head injury. Open head injury results in a focal contusion that occurs when the brain is directly insulted because of an opening in the skull. A gunshot wound is one example. In this instance, the skull is compromised and the projectile directly damages the brain. The most obvious case of this is a widely reported event from the nineteenth century. Phineas Gage was helping repair a railroad
and slammed a spike accidentally into a bit of dynamite. This propelled the spike through the soft tissue in his cheek, behind his eye sockets, and up through his forebrain.

Amazingly, besides the exit wound at the top of his head, he experienced no other bone fractures or damage to his optic nerve. Everything was intact except the part of brain the railroad spike sliced through. As a result of this, his personality completely changed. Normally a hard worker, he became abusive and crazed and was unable to control his behaviors. The area that sustained the most damage was the amygdala and the frontal cortex, both now known to temper our personalities. Studies of open head injury have helped us understand that some areas of the brain are specialized for certain functions. A lesion in the hypothalamus can cause someone to overeat; an injury a little below that and the person is hypersexual.

The major research on open head injury has been during wars. In World War I, one of the most common injuries was a gunshot wound to the head because of the trench warfare both sides were engaged in. On the German side, they favored leaving the wound open so it could breathe, but on the British and American side, the prevailing theory was debridement, or a closing of the wound. The American and British side prevailed in this war as well, as leaving the wound open usually resulted in an infection and death.