Basic Cell Biology

Basic Cell Biology for Parents of a Child with Down Syndrome

by Ginger Houston-Ludlam

This article is written for parents who have recently learned that their baby has Down syndrome. After I learned that my baby Carmen had Down syndrome, and after the shock wore off, I immediately set to work learning as much as I could about this condition. In the process, I learned about Targeted Nutritional Intervention, or TNI. I ordered a huge stack of literature about TNI. All of a sudden, I was faced with a great deal of Latin! It is important that parents understand what is happening inside their child’s body. Therefore, it helps to have some basic background in cell biology, and a little bit of biochemistry, before tackling all the Latin.

So, why is all this important? Well, the simple answer is that an extra copy of chromosome 21 lives in each cell of your child’s body. Much of the biochemical damage done by that extra chromosome happens in the cells.

So, I am going to discuss the various parts of the cell, paying special attention to the portions that seem to be most affected by the extra chromosome. I will also discuss general cell function, again focusing on the functions that are affected by Down syndrome. Finally, I will discuss the specific functions that are affected in nerve cells. I have tried to only give as much detail as I think is necessary to understand the basic issues of Down syndrome, and have aimed to describe things at a level detailed enough to be accurate and descriptive, but simple enough to be understood. For this reason, some things may be somewhat simplified, and much detail has been omitted. Also, I have included a glossary of words (all the long ones and the initials!) at the end of this essay.

Parts of the Cell

Nerve Cells

Conclusion

Parts of the Cell

The basic cell (see Figure 1) consists of a cell membrane (the covering around the outside of the cell), the cytoplasm (the liquid inside the cell where all the other parts of the cell float around), the nucleus (which in turn contains the DNA) and various “organelles,” which have specific jobs within the cell. I will not be focusing on any of the organelles, because, while important, an understanding of what they do specifically, or how they contribute to some of the chemistry, is not important in your understanding of the biochemical issues here.

Cell Membrane

The cell membrane (see Figure 2), while simple in its basic concept, is actually quite a complicated thing. It is primarily composed of “phospholipids”. The amazing thing about the phospholipid is that one end is attracted to water (the phosphate “head”), and the other end repels water (the fatty acid chains). When the phospholipids line up to form a cell membrane, they have the unique ability to keep both fat-based and water-based chemicals from passing through the membrane. The water-based stuff can’t get past the fatty acids, and the fat-based stuff can’t get past the phosphate group, in the same way that oil and water don’t mix. This means that all the big stuff (proteins, fats, and so forth) that belongs inside the cell stays there and everything that belongs outside the cell stays there. This is, in fact, the primary purpose for the membrane. At the same time the cell membrane controls these big molecules, it allows certain small chemicals to pass freely in and out of the cell, such as water, oxygen and carbon dioxide.

To get a picture in your mind of what a cell membrane looks like, imagine a bathtub covered with ping-pong balls, each of which has two strings hanging from it. The ping-pong balls are the phosphate heads and the strings are the fatty acid chains. It is important to imagine these ping-pong balls floating, because a cell membrane, in its healthy state, is indeed fluid, at about the same consistency as olive oil. Now imagine some larger balls floating in the bathtub amongst the ping-pong balls. Those are proteins that have specific jobs to do. Some of the proteins move special substances through the cell membrane, either to bring good stuff in (food, raw materials for chemical reactions), or to push bad stuff out (waste products). This process of moving things is called “transport” and it is a critical function of the cell membrane. However, for the transport to work correctly, the cell membrane must be fluid, because the protein changes shape as it grabs a molecule to pass in or out of the cell. If these proteins don’t have enough “elbow room” then they can’t do their job. As we will see later, one of the problems that Down syndrome causes is a loss of fluidity in the cell membranes, much as normal aging does, but much sooner than in genetically normal folks.

So, now let’s consider the impact of Down syndrome on the cell membrane. The fatty acid portions of the cell membrane are subject to chemical damage from a process called lipoperoxidation, or more generally, “oxidative stress.” There are many reasons for this, some of which will be discussed in the next section, after we have discussed the nucleus and DNA. The end result of this oxidative stress is that the cell membrane loses its fluidity, and therefore transport can’t operate correctly. When transport is not operating correctly, some chemicals can accumulate inside the cell, killing the cell. There are other needed chemicals that are stuck outside the cell, and the cell starves.

Vitamin E and some of the other vitamins have been included in NuTriVene-D specifically to protect against lipoperoxidation. Fatty acid supplements are included as part of the TNI protocol because giving healthy fatty acids will provide materials to repair the damaged cell membranes. Piracetam, a drug which can be included in the TNI protocol, also helps with the problem of oxidative damage to the cell membrane.

Nucleus

The next part of the cell that we need to look at is the nucleus. You might remember from high school Biology that the nucleus is where the DNA (Deoxyribonucleic Acid) lives in a cell. However, there is another thing that is relevant about the nucleus, and which is very important in understanding what is happening in Down syndrome. That is the process of “protein synthesis,” or the making of proteins. As the body goes about its daily life, it requires proteins for many things. For example, it requires enzymes to digest food, and it requires building materials to repair muscles, skin, etc. To make a protein, a portion of the DNA inside of the nucleus “unzips.” A section of RNA (a molecule similar to DNA, which is used in the making of proteins) is formed to match the unzipped DNA. Amino acids (the building blocks of proteins) are then strung together according to the instructions in the RNA to make the protein. Once the protein is made, it moves to the place in the cell where it is needed (or for that matter, it may leave the cell to go elsewhere) and goes to work doing whatever that protein is supposed to do.

This is one of the places where the extra chromosome 21 comes into play. Chromosomes are made of DNA. Because there is an extra copy of that chromosome in each cell of a person with Down syndrome, there is more DNA busy making proteins. More copies of proteins are produced than are needed for the normal chemical reactions that occur in a cell. In some cases, these extra proteins can cause metabolic imbalances, which lead to too much of some chemicals and not enough of others in the body.

A good example (and a fairly simple one to understand, but devastating in its effects) is the SOD gene, which is on chromosome 21. SOD stands for superoxide dismutase and it is half of a two-step process to take a poisonous form of oxygen, called superoxide, and turn it into oxygen and water. SOD, because it lives on chromosome 21, is made in larger quantity (the term used for this is “overexpressed”) than normal. The enzyme for the other half of this two-step process, glutathione peroxidase, is not overexpressed because it is on a different chromosome. (There is another enzyme that can work in place of glutathione peroxidase, called catalase. You may see either or both of these enzymes mentioned in when this process is discussed.) There is an imbalance, then. In step one, SOD takes the superoxide and turns it into hydrogen peroxide. But in step two, there isn’t enough glutathione peroxidase to break the hydrogen peroxide into oxygen and water fast enough. This leaves excess hydrogen peroxide hanging around in the cells. Unfortunately, hydrogen peroxide alone, if in a high enough concentration, is toxic to cells, especially nerve cells. This, incidentally, is why we use hydrogen peroxide on wounds. It is toxic to bacteria cells too.

The process by which hydrogen peroxide does its damage is called “oxidation,” and it is the same process that destroys the paint on your car, and turns cut apples and avocados brown. Furthermore, hydrogen peroxide also behaves badly when exposed to other chemicals in the body (such as iron) and can cause even more damage.

What is needed to address this problem is a variety of anti-oxidants, or chemicals (mostly vitamins and minerals) that keep the oxidative damage from happening, and in some cases, repair damage that has been done. The antioxidants in NuTriVene-D include Vitamins A (including beta-carotene), C, E, the minerals zinc and selenium and the supplements Alpha Lipoic Acid, Co-Q10, inositol and bioflavinoids. The drug piracetam also acts as an antioxidant, and helps to repair the loss of membrane fluidity.

Nerve Cells

Since nerve cells are so important to the understanding of the overall picture of Down syndrome, I am going to give a brief description of their structure and function. I am then going to discuss neurotransmitters, or the chemicals that are involved with the transmission of information from one nerve cell to the other. Of course, the various aspects of TNI that address these issues will be discussed as appropriate.

Structure of a Nerve Cell

The brain and spinal cord is heavily composed of nerve cells. There are some very significant differences between a nerve cell (”neuron”) and other cells in the body (see Figure 3). Think about this in terms of an octopus. First of all, neurons have a number of “tentacles” which stick out from the cell body. These tentacles are called dendrites, and they receive messages from other neurons. There is one more (usually longer) tentacle that sticks out from the cell body called the axon. This is the path that the message takes to be sent on to other neurons. There can be many dendrites on a neuron, but there is only one axon, and the nerve impulse always flows from a dendrite, through the cell body, and down the axon. At the end of the axon, the nerve branches out in multiple directions, and each of these branches connects to something else, such as another neuron, a muscle or an organ. The process of learning causes new connections to be made from one neuron to another. When connections are unused, they die off, or are “pruned” by the body.

One other significant difference between neurons and other cells is that mature neurons do not reproduce. Therefore, if a neuron is allowed to die (for example, by oxidative damage) then there will not be any way to replace it.

Finally, neuronal axons are often covered with a coating called myelin. This myelin is formed by another type of cell, called a glial cell, wrapping itself tightly around the axon. This myelin acts as an insulator (kind of like wrapping electrical tape around a live wire), and makes the neuron send the message more quickly, and keeps it from getting confused with impulses from neighboring neurons.

There is research which shows that starting at two months of age myelin formation slows in the brains of children with Down syndrome compared to genetically normal children. This research links delayed myelination of nerve cells with developmental delays. The glial cells which make up the myelin sheath have very little cytoplasm, therefore the myelin is made up almost entirely of the cell membranes of these glial cells. The cell membranes of these glial cells are made up of a lipid-protein mixture (slightly different than other types of cells) making the myelin have a higher proportion of lipids (fats) than any other type of cell in the body. A high percentage of these fats are in the form of docosahexaenoic acid, or DHA. DHA is one of the fatty acids supplemented as a part of the TNI protocol.

Function of Nerve Cells

When a neuron is stimulated, an electrical impulse is created, which travels down the dendrites, through the cell body and finally down the axon. At the end of the axon are bell-shaped little gadgets which “connect” to other things, in this case, other neurons. The bell-shaped gadgets are called synaptic knobs, and they hold chemicals called neurotransmitters. The synaptic knobs don’t actually touch the next neuron, but there is a tiny space between the two nerves called the synapse.

When the nerve impulse reaches the synaptic knob, the synaptic knob responds by releasing a neurotransmitter into the synapse. The next neuron detects the neurotransmitter through “receptors”, and if enough neurotransmitter has been released for that nerve to “fire,” it will do so, and the process repeats with the next neuron in the chain. After the neurotransmitter has been released into the synapse, the neurotransmitter is either slowly reabsorbed by the synaptic knob, or is destroyed by enzymes that live in the synapse. This keeps the receiving neuron from being incorrectly stimulated continuously. Neurons can be connected to, and therefore stimulate, other neurons, muscles (causing movement), glands (causing secretion of hormones and other chemicals) and organs.

Neurotransmitters

It’s time to focus on some particular neurotransmitters which seem to be particularly affected in Down syndrome. These are acetylcholine, serotonin, norpeinephrine and dopamine.

Acetlycholine. Acetylcholine has many functions in the body, including activation of muscle fiber, release of hormones, and learning/memory. The reason that acetylcholine is of interest to us is that there are fewer acetylcholine receptors in the brain in Down syndrome. It is thought that this contributes to some of the memory and learning problems seen in Down syndrome, because nerves are being stimulated less frequently. Finally, it may explain some of the endocrine (hormone) problems seen in Down syndrome, such as short stature, since release of Growth Hormone is affected by acetylcholine (essentially, the nerves are not talking to the portion of the brain that releases the hormone.) To counter this problem, supplementary choline and inositol is included in the TNI formula. These chemicals are used by the body to make acetylcholine.

Serotonin. Another neurotransmitter of interest in Down syndrome is serotonin. Serotonin controls peristalsis (the wave-like movements of the intestines which move food through as it is digested), and blood pressure, as well as being involved with control of behavior (especially mood and agression) and control of sleep-wake cycles. Levels of serotonin have been found to be reduced in people with Down Syndrome, both in the blood and in the cerebro-spinal fluid (the liquid that surrounds the brain and the spinal cord). L-tryptophan is supplemented in the nighttime formula portion of NuTriVene-D along with vitamin B-6. Tryptophan is an amino acid which is converted into serotonin inside the body, and which requires vitamins B-6 and C for that conversion.

Serotonin is also converted to Melatonin, which provides a proper deep state of sleep (called rapid eye movement, or REM sleep). During REM sleep, the brain is able to release its highest levels of Human Growth Hormone, which will improve growth. Ornithine is included in the nighttime formula to stimulate the release of Growth Hormone.

Dopamine. Dopamine, which has been found to be decreased in Down syndrome in some research articles but not others (in other words, the jury is still out on this one in terms of being affected in Down syndrome) is involved in high order association (bringing two separate pieces of information together in the brain), coordinating processes in the brain, and controlling movement. Tyrosine is a precursor to the production of dopamine, which is included in the NuTriVene-D formula.>

Norepinephrine. Dopamine is also converted to another neurotransmitter, called epinephrine, which is then converted to yet another one, called norepinephrine. Norepinephrine, also found to be decreased in Down syndrome, causes the brain to react to input from sensory organs, such as the eyes and ears. It, like serotonin, is also involved in regulating sleep-wake cycles as well as mood issues such as anxiety and arousal. Tyrosine from the NuTriVene-D formula is also provided to increase the levels of norepinephrine.

Conclusion

Down syndrome in many ways behaves like a degenerative disease. As such we have opportunities to intervene before the degeneration takes place, or to provide the body with the raw materials it needs to correct and repair the damage. This article has touched on a number of areas of the body which are affected by the extra chromosome. But research is proceeding at a furious pace, and new discoveries are being made every day. While there is no “cure” for Down syndrome waiting in the wings, we can certainly give our children the opportunity to live longer, happier, more capable lives than any prior generation of people with Down syndrome. By using multiple strategies—TNI to support health and development at a cellular level, and the various therapy approaches discussed in later sections of this book—there is nowhere to look but up as we all reach for the sky with our children.

Glossary

Chromosome. A strand of DNA which contains the code for specific genetic information. Chromosomes gather themselves up into bundles just prior to cell division.

DNA. (Deoxyribonucleic Acid) Where the genetic code for any living thing is stored.

Gene. A small portion of a strand of DNA that contains a single piece of information- such as the code needed for a particular protein in the body.

Lipoperoxidation. The process by which toxic forms of oxygen damage fats in the body, most notably the fatty acids in cell membranes.

Metabolism. The sum total of all the chemical reactions in the body.

Metabolic imbalance. The condition where too much of some chemicals and/or too few of other chemicals cause the body to operate incorrectly.

Neuron. A special type of cell used to transmit information within the brain and between the brain and the body.

Neurotransmitter. A chemical messenger used by nerve cells to communicate with each other.

Overexpression. More than a normal amount of a particular chemical (protein) is made because there are extra copies of the gene for that chemical.

Oxidation. The process by which molecules of toxic oxygen chemically alter, and damage, other chemicals.

Phospholipid. The combination of a phosphate molecule with two fatty acids. This type of chemical is the primary component of cell membranes.

Protocol. A set of medicines, chemicals or practices aimed at correcting a medical problem.

RNA (Ribonucleic Acid). A chemical structure similar to DNA that is involved in the process of protein synthesis.

SOD (Superoxide Dismutase). An enzyme that takes superoxide, a toxic form of oxygen, and converts it to hydrogen peroxide.

Superoxide. One of several toxic forms of oxygen, referred to collectively as free radicals.

Synapse. The space between neurons where neurotransmitters are used to communicate.

Synaptic knob. The small knob at the end of an axon where the neurotransmitter is stored and released during the process of communication between nerve cells.

From the book A Circle of Friends II, edited by Mullaly and Bolt, copyright 2000 A.D. Used by permission.