Neurological Research Has Identified Over 50 Kinds of Neurotransmitters

Neurological research has identified over 50 kinds of neurotransmitters. Scientists have found that several neurotransmitters are directly related to mental health problems. These specific neurotransmitters are Dopamine, Serotonin, Norepinephrine, and Gamma Aminobutyric Acid. A shortage or excess of these neurotransmitters are thought to be responsible for emotional disorders like anxiety, depression, ADHD, social anxiety and mood disorder.

Some examples of neurotransmitter action:

 Acetylcholine - voluntary movement of the muscles  Norepinephrine - wakefulness or arousal  Dopamine - voluntary movement and emotional arousal  Serotonin - memory, emotions, wakefulness, sleep and temperature regulation  GABA (gamma aminobutyric acid) - motor behaviour  Glycine - spinal reflexes and motor behaviour  Neuromodulators - sensory transmission-especially pain catecholamines  norepinephrine, epinephrine and dopamine.  exhibit peripheral nervous system excitatory and inhibitory effects as well as actions in the CNS such as respiratory stimulation and an increase in psychomotor activity  The excitatory effects are exerted upon smooth muscle cells of the vessels that supply blood to the skin and mucous membranes  Cardiac function is also subject to excitatory effects, which lead to an increase in heart rate and in the force of contraction  Inhibitory effects, by contrast, are exerted upon smooth muscle cells in the wall of the gut, the bronchial tree of the lungs, and the vessels that supply blood to skeletal muscle

Serotonin  (90%) is found in the enterochromaffin cells of the gastrointestinal tract  Most of the remainder of the body's 5HT is found in platelets and the CNS.  The effects of 5HT are felt most prominently in the cardiovascular system, with additional effects in the respiratory system and the intestines.  Vasoconstriction is a classic response to the administration of 5HT.  Reuptake  mediate platelet aggregation and smooth muscle contraction

 The 5HT2C receptors are suspected in control of food intake as mice lacking this gene become obese from increased food intake and are also subject to fatal seizures

 The 5HT3 receptors are present in the gastrointestinal tract and are related to vomiting.

 Also present in the gastrointestinal tract are 5HT4 receptors where they function in secretion and peristalsis.  The 5HT6 and 5HT7 receptors are distributed throughout the limbic system of the

brain and the 5HT6 receptors have high affinity for antidepressant drugs

GABA is a well-known inhibitor of presynaptic transmission in the CNS, and also in the retina  GABA-A receptors form a Cl- channel. The binding of GABA to GABA-A receptors increases the Cl- conductance of presynaptic neurons.  Gamma-aminobutyric acid (usually abbreviated to GABA) is an inhibitory neurotransmitter found in the nervous systems of widely divergent species. It is the chief inhibitory neurotransmitter in the vertebrate central nervous system

In vertebrates, GABA acts at inhibitory synapses in the brain. GABA acts by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neurons. This binding causes the opening of ion channels to allow either the flow of negatively-charged chloride ions into the cell or positively-charged potassium ions out of the cell. This will typically result in a negative change in the transmembrane potential, usually causing hyperpolarization.

Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate. Medium Spiny Cells are a typical example of inhibitory CNS GABAergic cells. GABA exhibits excitatory actions in insects, mediating muscle activation at synapses between nerves and muscle cells and also the stimulation of certain glands. In hippocampus and neocortex of the mammalian brain, GABA has primarily excitatory effects early in development, and is in fact the major excitatory neurotransmitter in many regions of the brain prior to the maturation of glutamate synapses. developing cortex. Whether GABA is excitatory or inhibitory depends on the direction (into or out of the cell) and magnitude of the ionic currents controlled by the

GABAA receptor. When net positive ionic current is directed into the cell, GABA is excitatory, when the net positive current is directed out of the cell, GABA is inhibitory. A developmental switch in the molecular machinery controlling the polarity of this current is responsible for the changes in the functional role of GABA between the neonatal and adult stages.

Drugs that act as agonists of GABA receptors (known as GABA analogues or GABAergic drugs) or increase the available amount of GABA typically have relaxing, anti-anxiety and anti-convulsive effects. Many of the substances below are known to cause short-term memory loss and retrograde amnesia.

Drugs that affect GABA receptors:

 alcohol (ethanol [1] [2])  barbiturates  opiates  cannabinoids Indolamines are a class of neurotransmitters which are all synthesized from the amino acid tryptophan. A common example of an indolamine is serotonin which is involved in mood and sleep. (Pinel 2006) In humans Indolamines are believed to be produced in the pineal gland, deep in the brain. Another example of an Indolamine - is Melatonin nitric oxide, which does not interact with membrane receptors but diffuse to target intracellular receptor

Dopamine

 similar to adrenaline and affects the brain processes that control movement, emotional response, and the capacity to feel pleasure and pain.  vital for performing balanced and controlled movements.  A shortage of dopamine can cause a lack of controlled movements such as those experienced in Parkinson disease.  moves into the frontal lobe and regulates the flow of information coming in from other areas of the brain. A shortage or problem with the flow of dopamine can cause a person to lose the ability to think rationally, demonstrated in schizophrenia.  an excess of dopamine in the limbic system and not enough in the cortex may produce a suspicious personality and possible paranoia.  A shortage of Dopamine in the frontal lobe can reduce one’s memory.  An increase of dopamine into the frontal lobe relieves pain and boosts feelings of pleasure.

Norepinephrine: a neurotransmitter in the catecholamine family that mediates chemical communicaion in the sympathetic nervous system,

 almost identical in structure to epinephrine, which is released into the bloodstream from the adrenal medulla under sympathetic activation.  The sympathetic nervous system functions in response to short-term stress; hence norepinephrine and epinephrine increase the heart rate as well as blood pressure.  Other actions of norepinephrine include increased glycogenolysis (the conversion of glycogen to glucose) in the liver,  increased lipolysis (the conversion of fats to fatty acids; see fats and oils) in adipose (fat) tissue  relaxation of bronchial smooth muscle to open up the air passages to the lungs. All of these actions represent a mobilization of the body’s resources in order to meet the stressful challenge—such a response is often termed the “flight or fight” syndrome. endorphins and enkephalins

 Chemical painkillers produced naturally in the body.  They are polypeptides, able to bind to the neuro-receptors in the brain to give relief from pain. This effect appears to be responsible for the so called runner's high, the temporary loss of pain when severe injury occurs, and the analgesic effects that acupuncture and chiropractic adjustments of the spine offer. (1)  enkephalins are pentapeptides, the smallest of the molecules with pain killing or opiate activity.  found in the thalamus of the brain and in parts of the spinal cord that transmit pain impulses  Endorphins may act to prevent the release of substance P, which may account for the sedating effects of endogenous endorphins and narcotics given exogeneously, such as heroin and morphine. A rise in blood levels of endorphins is measurable after exercise, and sexual activity. Our own opiates may explain how someone severely wounded in battle can continue to fight or have the strength to save someone else. Some scientists feel that endorphin release may be another reason some people pursue dangerous activities such as bungee jumping. So called thrill seekers and adrenaline junkies may not just be addicted to the rush of adrenaline. (2)

Pleasant memories such as our first bike, or a great vacation, or bad memories, as when a loved one or a pet dies are also linked to the autonomic nervous system and the brain stem. Endorphin research suggest a link between our emotional state of well being and the health of our immune systems. Endorphins and other neurotransmitters that are flooded into our bloodstream during stressful, as well as good times, are often felt "physically" as we get a queasy or nervous feeling in our stomachs. That "gut feeling" most people, at one time or another have felt, is our second brain talking to us, according to Jeff Cohen, M.D., a Kaiser Permanente neurologist. (4) The placebo effect is also attributed to endorphin and enkephalin release, as the emotional component of receiving a sugar pill. Many types of therapies such as massage or hydrotherapy's have also been shown to release endorphins and enkephalins. (2).

Nitric oxide serves many important functions in the cardiovascular system as summarized below:

 Vasodilation (ligand mediated and flow dependent)  Inhibition of vasoconstrictor influences (e.g., inhibits angiotensin II and sympathetic vasoconstriction)  Inhibition of platelet adhesion to the vascular endothelium (anti-thrombotic)  Inhibition of leukocyte adhesion to vascular endothelium (anti-inflammatory)  Antiproliferative (e.g., inhibits smooth muscle hyperplasia following vascular injury)  Scavenging superoxide anion (anti-inflammatory) When NO production is impaired as occurs when the vascular endothelium becomes damaged or dysfunctional, the following can result:

 Vasoconstriction (e.g., coronary vasospasm, elevated systemic vascular resistance, hypertension)  Platelet aggregation and adhesion leading to thrombosis  Upregulation of leukocyte and endothelial adhesion molecules leading to enhanced inflammation  Vascular stenosis, or restenosis as occurs following balloon angioplasty and stent placement  Increased inflammation and tissue damage mediated by reactive oxygen species such as superoxide anion and hydroxyl radical There is considerable evidence that the following diseases/conditions are associated with endothelial dysfunction and reduced NO production and/or bioavailability:  Hypertension  Obesity  Dyslipidemias (particularly hypercholesterolemia and hypertriglyceridemia)  Diabetes (both type I and II)  Heart failure  Atherosclerosis, cigarette smoking, aging, and vascular injury

The effects of carbon monoxide as a neurotransmitter.

Johnson RA, Johnson FK.

Department of Physiology, Tulane School of Medicine, New Orleans, Louisiana 70112, USA. [email protected]

Neural tissues generate carbon monoxide. Although neuronal carbon monoxide does not appear to be released in a directed manner, heme-derived carbon monoxide affects neuronally mediated activities. This rather suggests that endogenously formed carbon monoxide is an important neuromodulator. In addition, it appears that carbon monoxide may contribute to various neuropathological conditions. http://www.psych.org/pnews/00-07-07/neurotransmitter.html

Cocaine Physical mechanisms

 One significant effect of cocaine on the central nervous system is the blockage of the dopamine transporter protein (DAT). Dopamine transmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the pre-synaptic neuron, where it is taken up into storage vesicles.  Cocaine binds tightly at the DAT forming a complex that blocks the transporter's function. The DAT can no longer perform its reuptake function, and thus dopamine accumulates in the extracellular space (synaptic cleft).  This results in an enhanced and prolonged post-synaptic effect of dopaminergic signalling at dopamine receptors on the receiving neuron. Prolonged exposure to cocaine, as occurs with habitual use, leads to homeostatic dysregulation of normal (i.e., without cocaine) dopaminergic signaling via downregulation of D1 receptors and enhanced signal transduction.  The decreased dopaminergic signalling after chronic cocaine use may contribute to depressive mood disorders and sensitize this important brain reward circuit to the reinforcing effects of cocaine (e.g., enhanced dopaminergic signalling only when cocaine is self-administered). This sensitization contributes to the intractable nature of addiction and relapse.

Dopamine-rich brain regions such as the ventral tegmental area (VTA), nucleus accumbens (nAC), and prefrontal cortex (PFC) are frequent targets of cocaine addiction research. Of particular interest is the pathway consisting of dopaminergic neurons originating in the VTA that terminate in the nAC. This projection functions as a "reward center" in that it shows activation is response to drugs of abuse like cocaine in addition to natural rewards like food or sex (R Spanagel and F Weiss, The dopamine hypothesis of reward: past and current status. Trends Neurosci 22 (1999), pp. 521–527). While the precise role of DA in the subjective experience of reward is controversial among neuroscientists, the release of DA in the nAC is widely considered to be responsible for cocaine's rewarding effects. This conclusion is largely based on laboratory data involving rats that are trained to self- administer cocaine intravenously (i.v.). If DA antagonists are infused directly into the nAC, well-trained rats self-administering cocaine will undergo extinction (i.e., initially increase responding only to stop completely) thereby indicating that cocaine is no longer reinforcing (i.e., rewarding) the drug-seeking behavior.

Cocaine is also a less potent blocker of the norepinephrine transporter (NET) and serotonin transporter (SERT). Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials; thus, like lignocaine and novocaine, it acts as a local anesthetic. Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. The locomotor enhancing properties of cocaine may be attributable to its enhancement of dopaminergic transmission from the substantia nigra. Recent research points to an important role of circadian mechanisms[11] and clock genes[12] in behavioral actions of cocaine.

Because nicotine increases the levels of dopamine in the brain, many cocaine users find that consumption of tobacco products during cocaine use enhances the euphoria. This, however, may have undesirable consequences, such as uncontrollable chain smoking during cocaine use (even users who don't normally smoke cigarettes have been known to chain smoke when using cocaine), in addition to the detrimental health effects and the additional strain on the cardiovascular system caused by tobacco. In addition to irritability, mood disturbances, restlessness, paranoia, and auditory hallucinations, crack can cause several dangerous physical conditions. It can lead to disturbances in heart rhythm and heart attacks, as well as chest pains or even respiratory failure. In addition, strokes, seizures and headaches are common in heavy users.

Cocaine can often cause reduced food intake, many chronic users lose their appetite and can experience severe malnourishment and significant weight loss.

The mixture of cocaine and alcohol is the most common two-drug combination that results in drug related death

Disorders:

Psychosomatic illness

Alzheimers: a progressive degenerative disease

 Results in dementia, memory loss (recent)  Good natured become fool, moody, confused, hallucinations  Cognitive functions and memory areas have abnormal protein deposits and twisted fibers in neurons, brain atrophy

Parkinsons: a progressive nervous disease occurring most often after the age of 50, associated with the destruciton of brain cells that produce dopamine

 Muscle tremors  Slowing of movement  Partial facial paralysis  Peculiarity of gait and posture and weakness

Stroke: A sudden loss of brain function caused by a blockage or rupture of a blood vessel to the brain, ; cerebrovascular accident (CVA)

 Loss of muscle control  Diminution or loss of sensation or consciousness  Dizziness, slurred speech,

Concussion: a violent or jarring shaking, aninjury to a soft structure especially the brain, produced by a violent blow and followed by a temporary or prolonged loss of function

Contussion: marked tissue destruction

Cerebral edema: swelling due to intracranial hemorrhage Meningitis: inflammation of the menninges of the brain and spinal cord, mostoften the result of a bacterial or viral infection

 Fever, vomiting, intense headache and stiff neck

Encephalitis: inflammation of the brain

Lumbar puncture: a spinal tap, withdraw CSF, lay down 6-12 hours

Epidural: layer over the dura mater. An injection into the space between lumbar or sacral region of the spine

Spina bifida: a congenital defect in which the spinal column is imperfectly closed so that part of the meninges or spinal cord may protrude, often resulting in neurological disorders

 Cystica: protrusion of meninges or cord  Occulta: No protrusion

Anencephaly: congenital absence of most of the brain and spinal cord

Paralysis: loss of power of voluntary movement of a muscle through injury or disease through its nerve supply, loss of sensation over a region of the body

Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig's disease, is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells (neurons) responsible for controlling voluntary muscles. The disease belongs to a group of disorders known as motor neuron diseases, which are characterized by the gradual degeneration and death of motor neurons.

 both the upper motor neurons and the lower motor neurons degenerate or die, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, waste away (atrophy), and twitch (fasciculations) . Eventually, the ability of the brain to start and control voluntary movement is lost.  Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms. However, about 10 percent of ALS patients survive for 10 or more years.  Autoimmune, genetic, toxins, no one knows the cause but there is evidence for more than once cause adrenoleukodystrophy (ALD). It is a progressive degenerative myelin disorder, meaning that myelin, the "insulation" around nerves, breaks down over time. Without myelin, nerves can't function normally, or at all. Unfortunately, the body can't grow replacement myelin, so the disorder is progressive--it gets worse over time.

 inherited genetic disorder linked to the X sex chromosome.  disorder leaves the body unable to break down big fat molecules, either ones the body makes itself or ones that enter the body through food.  Recent research shows that this is most likely due to a carrier protein that fails to work correctly and carry the fat molecules to where they would be broken down. The fat molecules build up and clog up cells, and hurt nerve cells in the brain and spinal cord.

Polio spreads through human-to-human contact, usually through the mouth due to fecally contaminated water or food (fecal-oral transmission). Poliovirus enters the human body by penetrating the intestinal lining. From there, it enters into the lymphatic system via the Peyer's patches and the bloodstream via the mesentery and becomes a viremia.[6] The incubation period of polio, from the time of first exposure to first symptoms, is 2-20 days, with a range of 3 to 35 days. Following an initial infection (either apparent or inapparent) with poliovirus, virus particles are excreted in the feces for several weeks.[15] This increases transmission the disease, as the infected person may be unaware that they have had the disease, and make no effort to prevent passing it on to others.

A number of factors increase the risk of polio infection or affect the severity of the disease including: immune deficiency,[16] malnutrition,[17] intramuscular injection,[18] pregnancy, [18] and physical activity immediately following the onset of paralysis.[19]

During pregnancy, the virus can cross the placenta; however, it does not appear that the fetus is affected by either maternal infection with wild poliovirus, or by polio vaccination.[5] Protective maternal antibodies are also able to cross the placenta, providing passive immunity, and protect the infant from polio infection during the first few months of life.[20]