An Introduction
Neurochemistry: Why Life Depends On It.
Everyone knows that the brain is important, but most people don’t think about how it actually works. Ask anyone what the brain does and you will probably get a response along the lines of “It’s like the control center of the body; it thinks, and tells your body to move and stuff like that.” While this statement is true, it doesn’t explain how the brain works, or why it works.
Chemistry explains the “How, what, and why?” of the brain. While understanding the brain on a chemical level can get very complex, the basics are easy to comprehend with moderate knowledge in biology and chemistry. The anatomy and physiology of the brain are an important part of understanding neurochemistry. The chemistry of the brain is based largely on chemicals called neurotransmitters. There are many types of neurotransmitters which have various functions. Absence of neurotransmitters or abnormal neurotransmitter can explain several diseases. Many of these diseases are treated with drugs. Drugs, both medicinal and recreational, cause changes in neurotransmitters. Neurotransmitters are quite possibly some of the most important chemicals in our body because they control or regulate almost everything your body does.
In order to understand how the brain works, you need to understand some parts of neuroanatomy and physiology. It’s a safe assumption that almost everyone knows what the brain looks like; its overall shape roughly resembles a slanted question mark, and it is wrinkly. There are three main regions of the brain (forebrain, midbrain, hindbrain) which can be broken down into hundreds of subregions, each perform a variety of different tasks. The brain communicates through specialized cells called neurons. Neurons are very important. The primary nervous system (brain, brain stem, spinal cord) contains roughly 86 billion neurons (Williams, R. W. & Herrup). Different regions of the brain and body communicate via neurons. Neurons communicate to each other by “sending” chemicals to each other.
These chemicals of communication are known as neurotransmitters. Try to think of neurotransmitters as bits of information. When one neuron “sends” a neurotransmitter to another neuron it is received via a receptor site. A receptor site is a protein embedded in dendrite of the adjacent neuron. Dendrites are the “receiving” portion of the neuron. Once a neurotransmitter attaches to the receptor site, the receiving neuron either has an excitatory or inhibitory response. An excitatory response causes the neuron to send neurotransmitters; an inhibitory response stops the neuron from sending neurotransmitters. The technical terms for these responses are ESPS (excitatory post-synaptic potential) and ISPS (inhibitory post-synaptic potential). The soma (main body of a neuron cell), soma processes the incoming number ESPS and ISPS. The soma is the part of a neuron which synthesizes different types of neurotransmitters. The newly synthesized neurotransmitters are packaged in a bubble like structure called a vesicle. The vesicles of neurotransmitters are then sent down a long stretch of the neuron called the axon to the axon terminal. The axon terminal is the “sending” portion of a neuron (Kalat 30-45).
When a neuron receives enough ESPS, it creates an action potential. The mechanics of an action potential is purely chemical. Neurons contain high concentrations of potassium ions (K+) and very low concentrations of sodium ions (Na+). Conditions outside the neuron are the opposite (Na+ > K+). During an action potential, pores on the cell membrane open. These pores allow Na+ to flood into the cell, but K+ pores stay closed. This flood of ions creates an electrical charge. The charge moves down the axon to the axon terminal. Once the action potential (electrical charge) has reached the axon terminal, calcium ions enter the neuron which causes vesicles of neurotransmitters to be released into the synapse. The synapse is simply a space between an axon terminal of one neuron and the dendrite of another neuron. The neurotransmitters in the synapse attach to receptor sites where they create an ESPS or ISPS for the receiving neuron, and “communication” process starts over (Kalat 39-59). The difference between an ESPS and ISPS is determined completely by the specific type of neurotransmitter and receptor site.
The total number of neurotransmitters is unknown, new neurotransmitters are discovered very frequently. Some are more important than others. The neurotransmitters most commonly used by neurons belong to the following categories: amino acids, peptides, acetylcholine, monoamines, and purines (Kalat 59-60) The neurotransmitters in these categories are all organic molecules. Individual neurotransmitters within categories differ by functional groups. When neurotransmitters are released from the axon terminal into the synapse, they bind with receptor sites of the adjacent neuron or are “reabsorbed” by the releasing neuron. Each type of neurotransmitters binds with a very specific receptor site, although some receptor sites will bind with several types of neurotransmitters. Try to imagine putting a puzzle together, each piece has a certain place that it will fit; this is similar to the relationship between neurotransmitters and receptor sites. There are variations on each type of receptor site. For example, a neurotransmitter called serotonin (5-hydroxytryptamine, 5-HT) binds with receptor sites known as 5HT sites, but there are subtypes of 5-HT sites (ie: 5-HT2A, 5-HT2B). Neurotransmitters will bind with all of their respective receptor site subtypes, but different things happen depending on which subtype of the receptor the neurotransmitters binds with. An example to clarify: Serotonin binds with 5-HT receptor sites, but it can bind with 5-HT2A, 5-HT2B, etc. receptor site subtypes as well. Once a neurotransmitter binds with its respective receptor site, the “receiving” neuron is either excited or inhibited. Remember, a neuron must reach a certain amount of ESPS/ISPS before anything “happens.” Because one neuron may have thousands of different receptor sites, the result of what happens after binding becomes very complex. Most neurons communicate via complex, interconnected pathways to produce a result (ie: blinking). An excitation or inhibition of a neuron in a given pathway can cause an incredible amount of things to happen; again, this gets very complex. The complexity of neuronal networks and communication can lead to a variety of problems.
This variety of
problems that may arise may manifest itself as diseases. There are several mental
illnesses directly related to malfunctions in neurotransmitters. Parkinson’s disease is a prime example.
Parkinson’s is a neurodegenerative disease typically seen in elderly patients.
Its symptoms are muscle rigidity, partial paralysis and tremors. It is caused
by the death of dopamine and noradrenaline producing neurons (Nagatsu,
T. & Sawada, M.). Dopamine is a neurotransmitter that is related to
many types of disease. Parkinson’s disease occurs because there is not enough
dopamine in the brain. The result of an excess in dopamine can cause
schizophrenia, a disease which produces hallucinations (both audio and visual),
delusions, and paranoia. While the primary cause of schizophrenia is excess
dopamine, the complexity of pathways and other neurotransmitters play a large
role in this disease. There is
speculation that the NMDA glutamate receptor under-functions in schizophrenia
patients. Glutamate is a neurotransmitter that researchers believe somehow
interrupts the dopamine pathway causing an excess in dopamine (Coyle,
J.T.). Common diseases like depression are also related to
neurotransmitters. Depression caused, in part, by low serotonin levels.
Research suggests that 5-HT2A serotonin receptors are not working
properly in depressed patients. Aside from the receptor malfunction causing
depression, 5-HT2A sites are also associated with the mobilization
of calcium in the body. Problems with calcium mobilization can lead to other
diseases that do not directly correlate with neurology, such as cancer. (Uchitomi, Y., et al). There are countless other diseases which involve
neurotransmitter/receptor site malfunctions. Many types of toxins chemically
affect the neuron before they can even use neurotransmitters. One example is
scorpion venom. It attacks the nervous system by opening Na+ pores
and closing K+ pores. This ruins a neuron’s ability to fire action
potentials because the Na+ and K+ gradient must be
maintained or reestablished after the firing of an action potential (Pappone
& Cahalan). As made apparent, problems
with neurotransmitters and their receptor sites can have widespread and
devastating effects on the entire body.
Not all hope is lost though. There is plenty of research
being done in the neuroscience field, and drugs are being developed to help
people with diseases. A drug named L-DOPA supplies extra dopamine to a
Parkinson’s patient’s dopamine deficient mind. Clozapine, a treatment for
schizophrenia, blocks D4 receptor sites (Kalat 449). By blocking D4
sites, neurons that released dopamine are forced to take the dopamine back into
their cells (a process called reuptake). For depression, there is a whole range
of drugs. The most popular class of antidepressants is serotonin reuptake
inhibitors (SSRIs). These drugs prevent the reuptake of serotonin by blocking
the reuptake sites. By blocking reuptake sites serotonin is forced to stay in
the synapse until it is able to bind to a 5-HT receptor site. Examples of SSRIs
are Paxil®, Prozax®, Lexapro®, etc. Other
classes of antidepressant drugs are: tricyclics, monoamine oxidase inhibitors,
and atypical antidepressants. All antidepressant drugs target serotonin levels
in some manner except for the atypical class. Atypical antidepressants work on
a wide range of neurotransmitters that are known to contribute to depression.
These neurotransmitters include: epinephrine, norepinephrine, noradrenaline and
dopamine. Scientists are still working on finding out exactly which
neurotransmitters are involved in many diseases. Likewise, as they are
discovering new problems, they are developing newer, more efficient drugs.
Neurochemistry and neuroscience is an area that most people
would never think about. As it turns out though, neurochemistry is absolutely
vital to our lives. The anatomy and physiology of neurons is important in
understanding how the brain works. Neurotransmitters are vital chemicals that
the brain and body use to communicate. When things go wrong with
neurotransmitters and their receptor sites, diseases can arise. Because
neuroscience, neurochemistry, and psychopharmacology are continually doing new
research, treatments are becoming available for neurologically bases diseases.
The study and understanding of neurochemistry is continually working to improve
the quality of life and therefore society.
Coyle, J.T. “Glutamate and
Schizophrenia: Beyond the Dopamine Hypothesis”. Cellular and Molecular Neurobiology. (2006)
Kalat, J. W. “Biological
Psychology”. 7th ed. Wadsworth-Thomson Learning, Inc.
Nagatsu, T. & Sawada, M.
“Cellular and Molecular Mechanisms of Parkinson’s Disease: Neurotoxins,
Causative Genes,and Inflammatory Cytokines”. Cellular and Molecular Neurobiology. (2006).
Pappone & Cahalan. “Pandinus imperator Scorpion Venom Blocks
Voltage-Gated Potassium Channels in Nerve Fibers”. The Journal of Neuroscience. (1987). 7(10): 3300-3305
Uchitomi, Y., et al. “Three sets of diagnostic criteria for major depression and correlations with serotonin-induced platelet calcium mobilization in cancer patients”. Psychopharmacology. (2001). 153:244–248.
Williams, R. W. & Herrup. “Three-Dimensional Counting: An Accurate and Direct Method to Estimate Numbers of Cells in Sectioned Material”. Journal of Comparative Neurology. (1988). 278:344–352.