The development of the brain is a marvelous event that has, as yet, defied our ability to completely understand this God-given phenomenon. But we do know many intriguing things about this process. Basically, the brain must be constructed from a mere three layers of cells that differentiate into numerous types of specialized cells which in turn sprout out into trillions of spiny processes, each molded into a three-dimensional architecture of incredible exactness. During this intricate process, the brain makes far too many connections and must remove a large number of them by a process called pruning, just as you would prune a fruit tree. This pruning process is extremely precise and requires a critically timed release of higher concentrations of glutamate. Too much glutamate for too long a time and the brain will be overpruned; too little, and the connections will form a mass of confusing signals.
As this delicate molding process takes place, special enzymes make their appearance in the brain, again in a specifically timed sequence. Mercury, as an enzyme poison, interferes with this meticulous process, causing the brain to be "miswired." The process of miswiring can result in anything from mild behavioral and learning problems to major disorders such as autism and other forms of cerebral malfunction. Another way mercury seems to interfere with this process is by altering the careful balance of calcium within the cell. We know that calcium passing into the cell, and within compartments of the cell, plays a major role in the transmission of signals that direct the development process as well as neuron function.
In part, special bulbs, called growth cones, located at the end of the neural fibers direct this process of neural pathway development in the brain. These specialized cones direct the nerve fiber to its correct location in the three-dimensional maze that makes up the immature brain. How the growth cone does this depends to a large degree on calcium, and heavy metals like mercury and cadmium interfere with this calcium-directed process. As a result, the nerve fiber gets lost and the brain is miswired. The final effect of this miswiring process depends on the severity of the miswiring. Mercury has been shown to affect this growth process at concentrations in the micromolar or even sub-micromolar range.34 In other words, it happens with exposures that are extremely small.
In simple terms, the reason for this disorganization of brain development is that mercury poisons the chemicals used to induce these cells to migrate to their assigned locations. Brain cells normally align themselves in functional columns, which on stained slides have beauti fully layered patterns of light and dark. In the past, neuroscientists classified these patterns in elaborate maps (cytoarchitectonic maps). The process of brain development is very complex and beyond the scope of this book, but basically we know that toxins, like heavy metals, can disrupt many of the intricate steps in brain formation.35
As you know by now, one of the central processes in brain injuries and degeneration is the formation of free radicals. For example, in Down's syndrome there is a fourfold increase in these destructive particles.36 A recent study found that exposure of brain neurons (caudate, hippocampus, cerebellum, and frontal cortex) to as little as 1-5 uM of methylmercury significantly increased free-radical generation in all of the cells.37 A micromole is one-millionth of a mole weight, an infinitesimally small amount of mercury.
One of the ways mercury induces free-radical formation is by damaging a cell's mitochondria.38 Because of this loss of energy-producing capacity, the neuron becomes infinitely more susceptible to excitotoxic injury and death even in the presence of normal levels of the neurotransmitter, glutamate. The cycle continues until the cells begin to die or the dendritic fibers shrink. It is these dendritic fibers that make the trillions of connections in the brain.
Destruction of the spiny dendrites can occur independent of the death of the neuron. This is especially important when considering chronic exposure to very low concentrations of mercury. By removing the mercury and supplying nutrients to the neuron, we may be able to regrow these dendritic spines that are so critical to brain function. Synapses are also very sensitive to free-radical injury and lipid peroxidation.
Neurotransmitters, like most other things in the brain, appear in a set pattern, a sequence which is carefully controlled during brain development but can be disrupted by environmental toxins such as mercury. For example, mercury has been shown to cause a sudden release of acetylcholine in the brain, which can not only interrupt developmental signals but can be directly neurotoxic.39
It has been well-demonstrated that even minor changes in the structure or function of these cells, or their processes, can have profound consequences on behavioral, neurological and learning functions, as well as other body functions. It must be remembered that the nervous system connects to all parts of the body and exerts either a direct or an indirect influence on body function. For example, the brain has intimate bi-directional connections with the immune system, endocrine system, and gastrointestinal tract. We know that MSG-induced injuries in a newborn's hypothalamus can result in profound depression of the immune system that may last a lifetime. The same is true for endocrine malfunction; that is, we see a loss of the normal flow of growth hormone, reproductive hormones, and adrenal hormones with MSG-type hypothalamic injuries.
When we consider the effects of small concentrations of mercury on the developing brain, we must appreciate the subtle effects that can result. Medical science generally assumes a substance is safe if it does not cause an obvious abnormality on neurological function or behavior. For example, if a substance does not cause a seizure, loss of movement, or obviously impaired learning, it is considered generally safe. Unfortunately, this is very naive and dangerous thinking. The human brain is a very complex structure that can withstand significant injuries with only subtle changes in function, yet even these subtle effects can have a devastating impact on our children's ability to function normally throughout life.
But of special concern is mercury's ability to do two things in the brain. One is to activate the brain's immune system (microglia), and another is to poison the glutamate re-uptake system.
The amino acid, glutamate, is used by the brain as a neurotransmitter, mainly to cause excitation of special brain cells, used for communication between neurons. But, overex-citing the brain can also be very dangerous: it can lead to seizures, and destruction of brain cells by a process called excitotoxicity. For this reason, the amount of free glutamate allowed to move around in the brain's extracellular spaces is carefully controlled by the brain under normal circumstances.
This control system involves a family of protein-carrier molecules whose job it is to bind with the free glutamate and carry it to a nearby cell called an astrocyte, where the glutamate is safely stored. Even microscopic increases in free glutamate can trigger a destructive process that causes neurons to commit suicide. Under certain conditions, even normal levels of glutamate can kill brain cells.
Mercury is unique among metals in that it can selectively block the glutamate re-uptake system, even when present in incredibly small concentrations. When the system is blocked, free glutamate accumulates in the brain's extracellular spaces, triggering excitotoxicity. The glutamate transporter continues to be impaired since mercury stays in the brain for such long periods of time.
We know that the infant brain is four times more sensitive than the adult brain to excitotoxicity. This is because many of the infant brain's protective systems are immature and poorly developed. Not surprisingly, glutamate plays a critical role in brain circuitry formation, including the operation of the growth cones that guide neural fibers in the developing brain.
Introduction of mercury during this delicate process can cause glutamate levels to rise too soon or accumulate in high concentrations, resulting in miswiring of the brain. The effects of this miswiring can be subtle or devastating, depending on many conditions: the dose of the mercury, when it was given, and the nutritional status of the baby.
Subtle changes may result in minor behavioral problems, such as some difficulty with memory and cognition, or a loss of anger control. As a child, these conditions may be classed as attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), or one of autism spectrum disorders. In more severe cases, the damage may result in full-blown autism or Asperger's syndrome. As we shall see in chapter seven, early changes in glutamate levels can also disrupt the endocrine system, resulting in reproductive problems, hypothyroidism, and adrenal gland malfunction later in life.
58 • Health and Nutrition Secrets That Can Save Your Life Localization of Mercury in the Immature Brain
Acute, high-dose, mercury poisoning in adults is characterized by a localization of the toxin in the occipital lobes of the brain, especially in an area called the calcarine cortex, which is the part of the brain controlling vision. This may explain the loss of color vision and tunnel vision seen in mercury miners. Remember that the cerebellum is a primary site of localization of mercury in both adults and children. Chronic exposure in children has a somewhat different brain deposition, with localization more commonly found in the amygdala, neocortex, and temporal lobes.40
Significant but lower accumulations of mercury also occur in other parts of the brain. In children exposed to high-dose mercury, we see widespread destruction of neurons in the brain accompanied by scarring (called gliosis), but more importantly we see grossly abnormal development of brain-cell layers (referred to as the cytoarchitecture of the brain) with isolated clumps of malformed brain cells and disorganization of the cells in the cortex of the brain.41 This was the sort of damage seen in the Iraq and Minamata poisonings.
Most studies of mercury's effect on brain development have concentrated on methylmercury rather than inorganic mercury, but, as we have seen, dental amalgam releases both methylmercury and inorganic mercury, and within the brain methylmercury can undergo
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