IVMS Neuro-Neurotransmitters Overview / Review

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Neurotransmitter

Retrieved and modified from"http://en.wikipedia.org/w/index.php?title=Neurotransmitter&oldid=556935683 "Categories:

Neurotransmitters Molecular neuroscience

Neuroscience

Structure of a typical chemical synapse

Neurotransmitters are endogenous chemicals that transmit signals from a neuron to atarget cell across a synapse.[1]Neurotransmitters are packaged into synaptic vesiclesclustered beneath the membrane in the axon terminal, on the presynaptic side of asynapse. They are released into and diffuse across the synaptic cleft, where they bindto specific receptors in the membrane on the postsynaptic side of the synapse.

[2]

Release of neurotransmitters usually follows arrival of an action potential at thesynapse, but may also follow graded electrical potentials. Low level "baseline" releasealso occurs without electrical stimulation. Many neurotransmitters are synthesized fromplentiful and simple precursors, such as amino acids, which are readily available fromthe diet and which require only a small number of biosynthetic steps to convert.[3]

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Discovery

Until the early 20th century, scientists assumed that the majority of synapticcommunication in the brain was electrical. However, through the careful histologicalexaminations ofRamn y Cajal (18521934), a 20 to 40 nm gap between neurons,

known today as the synaptic cleft, was discovered. The presence of such a gapsuggested communication via chemical messengers traversing the synaptic cleft, and in1921 German pharmacologist Otto Loewi (18731961) confirmed that neurons cancommunicate by releasing chemicals. Through a series of experiments involving thevagus nerves of frogs, Loewi was able to manually slow the heart rate of frogs bycontrolling the amount of saline solution present around the vagus nerve. Uponcompletion of this experiment, Loewi asserted that sympathetic regulation of cardiacfunction can be mediated through changes in chemical concentrations. Furthermore,Otto Loewi is accredited with discovering acetylcholine (ACh)the first knownneurotransmitter.

[4]Some neurons do, however, communicate via electrical synapses

through the use ofgap junctions, which allow specific ions to pass directly from one cell

to another.[5]

Identifying neurotransmitters

The chemical identity of neurotransmitters is often difficult to determine experimentally.For example, it is easy using an electron microscope to recognize vesicles on thepresynaptic side of a synapse, but it may not be easy to determine directly whatchemical is packed into them. The difficulties led to many historical controversies overwhether a given chemical was or was not clearly established as a transmitter. In aneffort to give some structure to the arguments, neurochemists worked out a set of

experimentally tractable rules. According to the prevailing beliefs of the 1960s, achemical can be classified as a neurotransmitter if it meets the following conditions:

There are precursors and/or synthesis enzymes located in the presynaptic sideof the synapse.

The chemical is present in the presynaptic element. It is available in sufficient quantity in the presynaptic neuron to affect the

postsynaptic neuron. There are postsynaptic receptors and the chemical is able to bind to them. A biochemical mechanism for inactivation is present.

Modern advances in pharmacology, genetics, and chemical neuroanatomy have greatlyreduced the importance of these rules. A series of experiments that may have takenseveral years in the 1960s can now be done, with much better precision, in a fewmonths. Thus, it is unusual nowadays for the identification of a chemical as aneurotransmitter to remain controversial for very long periods of time.

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Types of neurotransmitters

There are many different ways to classify neurotransmitters. Dividing them into aminoacids, peptides, and monoamines is sufficient for some classification purposes.

Major neurotransmitters:

Amino acids: glutamate,[3] aspartate, D-serine,-aminobutyric acid (GABA),

glycine Monoamines and otherbiogenic amines: dopamine (DA), norepinephrine

(noradrenaline; NE, NA), epinephrine (adrenaline), histamine, serotonin (SE, 5-HT)

Peptides:somatostatin, substance P, opioid peptides[6]

Others: acetylcholine (ACh), adenosine, anandamide, nitric oxide, etc.

In addition, over 50 neuroactive peptides have been found, and new ones arediscovered regularly. Many of these are "co-released" along with a small-moleculetransmitter, but in some cases a peptide is the primary transmitter at a synapse.-endorphin is a relatively well known example of a peptide neurotransmitter; it engagesin highly specific interactions with opioid receptors in the central nervous system.

Single ions, such as synaptically released zinc, are also considered neurotransmittersby some,[7]as are some gaseous molecules such as nitric oxide (NO), hydrogen sulfide(H2S), and carbon monoxide (CO).

[8]Because they are not packaged into vesicles they

are not classical neurotransmitters by the strictest definition, however they have all beenshown experimentally to be released by presynaptic terminals in an activity-dependentway.

By far the most prevalent transmitter is glutamate, which is excitatory at well over 90%of the synapses in the human brain.[3]The next most prevalent is GABA, which isinhibitory at more than 90% of the synapses that do not use glutamate. Even thoughother transmitters are used in far fewer synapses, they may be very importantfunctionallythe great majority of psychoactive drugs exert their effects by altering theactions of some neurotransmitter systems, often acting through transmitters other thanglutamate or GABA. Addictive drugs such as cocaine and amphetamine exert their

effects primarily on the dopamine system. The addictive opiate drugs exert their effectsprimarily as functional analogs ofopioid peptides, which, in turn, regulate dopaminelevels.

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Excitatory and inhibitory

Some neurotransmitters are commonly described as "excitatory" or "inhibitory". The onlydirect effect of a neurotransmitter is to activate one or more types of receptors. Theeffect on the postsynaptic cell depends, therefore, entirely on the properties of those

receptors. It happens that for some neurotransmitters (for example, glutamate), themost important receptors all have excitatory effects: that is, they increase the probabilitythat the target cell will fire an action potential. For other neurotransmitters, such asGABA, the most important receptors all have inhibitory effects (although there isevidence that GABA is excitatory during early brain development). There are, however,other neurotransmitters, such as acetylcholine, for which both excitatory and inhibitoryreceptors exist; and there are some types of receptors that activate complex metabolicpathways in the postsynaptic cell to produce effects that cannot appropriately be calledeither excitatory or inhibitory. Thus, it is an oversimplification to call a neurotransmitterexcitatory or inhibitorynevertheless it is convenient to call glutamate excitatory andGABA inhibitory so this usage is seen frequently.

Actions

Main article:Neuromodulation

As explained above, the only direct action of a neurotransmitter is to activate a receptor.Therefore, the effects of a neurotransmitter system depend on the connections of theneurons that use the transmitter, and the chemical properties of the receptors that thetransmitter binds to.

Here are a few examples of important neurotransmitter actions:

Glutamateis used at the great majority of fast excitatory synapses in the brainand spinal cord. It is also used at most synapses that are "modifiable", i.e.capable of increasing or decreasing in strength. Excess glutamate canoverstimulate the brain and causes seizures.[ Modifiable synapses are thought tobe the main memory-storage elements in the brain. Excessive glutamate releasecan lead to excitotoxicity causing cell death.

GABAis used at the great majority of fast inhibitory synapses in virtually everypart of the brain. Many sedative/tranquilizing drugs act by enhancing the effectsof GABA. Correspondingly glycine is the inhibitory transmitter in the spinal cord.

Acetylcholineis distinguished as the transmitter at the neuromuscular junction

connecting motor nerves to muscles. The paralytic arrow-poison curare acts byblocking transmission at these synapses. Acetylcholine also operates in manyregions of the brain, but using different types of receptors, including nicotinic andmuscarinic receptors.[9]

Dopaminehas a number of important functions in the brain; this includesregulation of motor behavior, pleasures related to motivation and also emotionalarousal. It plays a critical role in the reward system; people with Parkinson's

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disease have been linked to low levels of dopamine and people withschizophrenia have been linked to high levels of dopamine.[10]

Serotoninis a monoamine neurotransmitter. Most is produced by and found inthe intestine (approximately 90%), and the remainder in central nervous systemneurons. It functions to regulate appetite, sleep, memory and learning,

temperature, mood, behaviour, muscle contraction, and function of thecardiovascular system and endocrine system. It is speculated to have a role indepression, as some depressed patients are seen to have lower concentrationsof metabolites of serotonin in theircerebrospinal fluid and brain tissue.[11]

Substance Pis an undecapeptide responsible for transmission of pain fromcertain sensory neurons to the central nervous system. It also aids in controllingrelaxation of the vasculature and lowering blood pressure through the release ofnitric oxide.[12]

Opioid peptidesare neurotransmitters that act within pain pathways and theemotional centers of the brain; some of them are analgesics and elicit pleasureor euphoria.[13]

Neurons expressing certain types of neurotransmitters sometimes form distinctsystems, where activation of the system affects large volumes of the brain, calledvolume transmission. Major neurotransmitter systems include the noradrenaline(norepinephrine) system, the dopamine system, the serotonin system and thecholinergic system.

Drugs targeting the neurotransmitter of such systems affect the whole system; this factexplains the complexity of action of some drugs. Cocaine, for example, blocks thereuptake ofdopamine back into the presynaptic neuron, leaving the neurotransmittermolecules in the synaptic gap longer. Since the dopamine remains in the synapse

longer, the neurotransmitter continues to bind to the receptors on the postsynapticneuron, eliciting a pleasurable emotional response. Physical addiction to cocaine mayresult from prolonged exposure to excess dopamine in the synapses, which leads to thedownregulation of some postsynaptic receptors. After the effects of the drug wear off,one might feel depressed because of the decreased probability of the neurotransmitterbinding to a receptor. Prozac is a selective serotonin reuptake inhibitor(SSRI), whichblocks re-uptake of serotonin by the presynaptic cell. This increases the amount ofserotonin present at the synapse and allows it to remain there longer, hencepotentiating the effect of naturally released serotonin.[14] AMPT prevents the conversionof tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopaminestorage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thusincreases dopamine levels.

Diseases may affect specific neurotransmitter systems. For example, Parkinson'sdisease is at least in part related to failure of dopaminergic cells in deep-brain nuclei, forexample the substantia nigra. Levodopa is a precursor of dopamine, and is the mostwidely used drug to treat Parkinson's disease.

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A brief comparison of the major neurotransmitter systems follows:

Neurotransmitter systems

System Origin[15] Effects[15]

Noradrenalinesystem

locus coeruleus arousal

rewardLateral tegmental field

Dopaminesystem

dopamine pathways:

mesocortical pathway mesolimbic pathway

nigrostriatal pathway tuberoinfundibular

pathway

motor system, reward, cognition, endocrine,nausea

Serotoninsystem

caudal dorsal raphe nucleus Increase (introversion), mood, satiety, body

temperature and sleep, while decreasingnociception.rostral dorsal raphe nucleus

Cholinergicsystem

pontomesencephalotegmentalcomplex

learning short-term memory arousal

rewardbasal optic nucleus of Meynert

medial septal nucleus

Common neurotransmitters

Category Name AbbreviationMetabotropic Ionotropic

Small: Amino acids Aspartate - -

Neuropeptides N-Acetylaspartylglutamate

NAAG

Metabotropicglutamatereceptors;selective agonistofmGluR3

-

Small: Amino acidsGlutamate (glutamicacid)

GluMetabotropicglutamatereceptor

NMDA receptor,Kainate receptor,AMPA receptor

Small: Amino acidsGamma-aminobutyricacid

GABA GABAB receptorGABAA, GABAA-receptor

Small: Amino acids Glycine Gly - Glycine receptor

Small: Acetylcholine Acetylcholine AchMuscarinicacetylcholinereceptor

Nicotinicacetylcholinereceptor

Small: Monoamine(Phe/Tyr)

Dopamine DADopaminereceptor

-

Small: Monoamine Norepinephrine NE Adrenergic -

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Category Name AbbreviationMetabotropic Ionotropic

(Phe/Tyr) (noradrenaline) receptor

Small: Monoamine(Phe/Tyr)

Epinephrine (adrenaline) EpiAdrenergicreceptor

-

Small: Monoamine(Phe/Tyr) Octopamine

- -

Small: Monoamine(Phe/Tyr)

Tyramine -

Small: Monoamine(Trp)

Serotonin (5-hydroxytryptamine)

5-HTSerotoninreceptor, all but 5-HT3

5-HT3

Small: Monoamine(Trp)

Melatonin MelMelatoninreceptor

-

Small: Diamine(His)

Histamine HHistaminereceptor

-

PP: Gastrins Gastrin

- -

PP: Gastrins Cholecystokinin CCKCholecystokininreceptor

-

PP:Neurohypophyseals

Vasopressin AVPVasopressinreceptor

-

PP:Neurohypophyseals

Oxytocin OT Oxytocin receptor -

PP:Neurohypophyseals

Neurophysin I - -

PP:Neurohypophyseals

Neurophysin II - -

PP: Neuropeptide Y Neuropeptide Y NYNeuropeptide Yreceptor

-

PP: Neuropeptide Y Pancreatic polypeptide PP - -

PP: Neuropeptide Y Peptide YY PYY - -

PP: OpioidsCorticotropin(adrenocorticotropichormone)

ACTHCorticotropinreceptor

-

PP: Opioids Dynorphin - -

PP: Opioids Endorphin - -

PP: Opioids Enkephaline - -

PP: Secretins Secretin Secretin receptor -

PP: Secretins Motilin Motilin receptor -

PP: Secretins Glucagon Glucagonreceptor

-

PP: SecretinsVasoactive intestinalpeptide

VIPVasoactiveintestinal peptidereceptor

-

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Category Name AbbreviationMetabotropic Ionotropic

PP: SecretinsGrowth hormone-releasing factor

GRF - -

PP: Somatostatins Somatostatin Somatostatinreceptor

-

SS: Tachykinins Neurokinin A - -

SS: Tachykinins Neurokinin B - -

SS: Tachykinins Substance P - -

PP: Other Bombesin - -

PP: OtherGastrin releasingpeptide

GRP - -

Gas Nitric oxide NOSoluble guanylylcyclase

-

Gas Carbon monoxide CO -Heme bound topotassium

channels

Other Anandamide AEACannabinoidreceptor

-

Other Adenosine triphosphate ATP P2Y12 P2X receptor

Precursors of neurotransmitters

While intake of neurotransmitterprecursors does increase neurotransmitter synthesis,evidence is mixed as to whetherneurotransmitter release (firing) is increased. Even withincreased neurotransmitter release, it is unclear whether this will result in a long-term

increase in neurotransmitter signal strength, since the nervous system can adapt tochanges such as increased neurotransmitter synthesis and may therefore maintainconstant firing.[16]Some neurotransmitters may have a role in depression, and there issome evidence to suggest that intake of precursors of these neurotransmitters may beuseful in the treatment of mild and moderate depression.[16][17]

Dopamine precursors

L-DOPA, a precursor ofdopamine that crosses the bloodbrain barrier, is used in thetreatment ofParkinson's disease.

Norepinephrine precursors

For depressed patients where low activity of the neurotransmitternorepinephrine isimplicated, there is only little evidence for benefit of neurotransmitter precursoradministration. L-phenylalanine and L-tyrosine are both precursors fordopamine,norepinephrine, and epinephrine. These conversions require vitamin B6, vitamin C, andS-adenosylmethionine. A few studies suggest potential antidepressant effects of L-phenylalanine and L-tyrosine, but there is much room for further research in this area.[16]

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Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum".Cell135 (5): 825837.doi:10.1016/j.cell.2008.09.059.PMC2614332.PMID19041748.

15. Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. pp. 474 fornoradrenaline system, page 476 for dopamine system, page 480 for serotonin

system and page 483 for cholinergic system.ISBN0-443-07145-4.16. Meyers, Stephen (2000)."Use of Neurotransmitter Precursors for Treatment ofDepression".Alternative Medicine Review5 (1): 6471.PMID10696120.

17. Van Praag, HM (1981). "Management of depression with serotonin precursors".Biol Psychiatry16 (3): 291310.PMID6164407.

External links

Molecular Expressions Photo Gallery: The Neurotransmitter Collection Brain Neurotransmitters Endogenous Neuroactive Extracellular Signal Transducers

Neurotransmitterat the US National Library of MedicineMedical SubjectHeadings(MeSH) neuroscience for kids website brain explorer website wikibooks cellular neurobiology

Supplemental: An overview of neurotransmitters for non-biomedical science

learners

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Source:http://www.integrativepsychiatry.net/neurotransmitter.html

The Four Major Neurotransmitters

Neurotransmitters are powerful chemicals that regulate numerous physical andemotional processes such as mental performance, emotional states and pain response.Virtually all functions in life are controlled by neurotransmitters. They are the brain'schemical messengers.Interactions between neurotransmitters, hormones, and the brainchemicals have a profound influence on overall health and well-being. When ourconcentration and focus is good, we feel more directed, motivated, and vibrant.Unfortunately, if neurotransmitter levels are inadequate these energizing and motivatingsignals are absent and we feel more stressed, sluggish, and out-of-control.

Proteins, minerals, vitamins,carbohydrates, and fats are the essential nutrients thatmake up your body. Proteins are the essential components of muscle tissue, organs,blood, enzymes, antibodies, and neurotransmitters in the brain. Your brain needs theproper nutrients everyday in order to manufacture proper levels of the neurotransmittersthat regulate your mood.

Neurotransmitter Effects:

Control the appetite center of the brainStimulates Corticotropin Releasing Factor, Adrenalcorticotropic Hormone, & CortisolRegulate male and female sex hormoneRegulates sleepModulate mood and thought processesControls ability to focus, concentrate, and remember thingsThe Mind Body ConnectionThe chemistry of our bodies can alter, and be altered by our every thought and feeling.Our bodies and our minds are truly interconnected, the health of one depends on thehealth of the other.

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There are many biochemical neurotransmitter imbalances that result in mentalhealth symptoms such as:

*Adrenal dysfunction *Blood sugar imbalance

*Food and Chemical allergy *Heavy Metal Toxicity *Hormone imbalance *NutritionalDeficiency *Serotonin/Dopamine/Noradrenalin imbalance *Stimulant and drug intoxication *Under or overactive thyroid

Neurotransmitter Imbalances

Disrupted communication between the brain and the body can have serious effects to

ones health both physically and mentally. Depression, anxiety and other mood disordersare thought to be directly related to imbalances with neurotransmitters. The four majorneurotransmitters that regulate mood are Serotonin, Dopamine, GABA andNorepinephrine.

The Inhibitory System is the brains braking system, it prevents the signal fromcontinuing. The inhibitory system slows things down. Serotonin and GABA areexamples of inhibitory neurotransmitters.

GABA (Gamma amino butyric acid) GABA is the major inhibitory neurotransmitter in thecentral nervous system. It helps the neurons recover after transmission, reduces anxiety

and stress.It regulates norepinephrine, adrenaline, dopamine, and serotonin, it is asignificant mood modulator.

Serotonin imbalance is one of the most commoncontributors to mood problems. Some feel it is a virtualepidemic in the United States. Serotonin is key to ourfeelings of happiness and very important for our emotionsbecause it helps defend against both anxiety anddepression. You may have a shortage of serotonin if youhave a sad depressed mood, anxiety, panic attacks, lowenergy, migraines, sleeping problems, obsession or

compulsions, feel tense and irritable, crave sweets, andhave a reduced interest in sex. Additionally, your hormonesand Estrogen levels can affect serotonin levels and thismay explain why some women have pre-menstrual andmenopausal mood problems. Moreover, daily stress can greatly reduce your serotoninsupplies.

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The Excitatory Neurotransmitter System can be related to your car's accelerator. Itallows the signal to go. When the excitatory neurotransmitter system is in drive yoursystem gets all reved up for action. Without a functioning inhibitory system to put on thebrakes, things (like your mood) can get out of control

Epinephrine also known as adrenaline is a neurotransmitter and hormone essential tometabolism. It regulates attention, mental focus, arousal, and cognition. It also inhibitsinsulin excretion and raises the amounts of fatty acids in the blood. Epinephrine is madefrom norepinephrine and is released from the adrenal glands. Low levels have been canresult in fatigue, lack of focus, and difficulty losing weight. High levels have been linkedto sleep problems, anxiety and ADHD.

Dopamine is responsible for motivation, interest, and drive. It is associated with positivestress states such as being in love, exercising, listening to music, and sex . When wedon't have enough of it we don't feel alive, we have difficulty initiating or completingtasks, poor concentration, no energy, and lack of motivation. Dopamine also is involved

in muscle control and function. Low Dopamine levels can drive us to use drugs (selfmedicate), alcohol, smoke cigarettes, gamble, and/or overeat. High dopamine has beenobserved in patients with poor GI function, autism, mood swings, psychosis, andchildren with attention disorders.

Glutamate is the major excitatory neurotransmitter in the brain. It is required forlearning and memory. Low levels can lead to tiredness and poor brain activity.Increased levels of glutamate can cause death to the neurons (nerve cells) in the brain.Dysfunction in glutamate levels are involved in many neurodegenerative diseases suchas Alzheimer's disease, Parkinson's, Huntington's, and Tourette's. High levels alsocontribute to Depression, OCD, and Autism.

Histamine is most commonly known for it's role in allergic reactions but it is alsoinvolved in neurotransmission and can affect your emotions and behavior as well.Histamine helps control the sleep-wake cycle and promotes the release of epinephrineand norepinephrine. High histamine levels have been linked to obsessive compulsivetendencies, depression, and headaches.Low histamine levels can contribute toparanoia, low libido, fatigue, and medication sensitivities.

Norepinephrine also known as noradrenaline is a excitatory neurotransmitter that isproduced by the adrenal medulla or made from dopamine. High levels of norepinephrineare linked to anxiety, stress, high blood pressure, and hyperactivity. Low levels arelinked to lack of energy, focus, and motivation.

PEA is an excitatory neurotransmitter made from phenylalanine. It is important in focusand concentration. High levels are observed in individuals experiencing "mind racing",sleep problems, anxiety, and schizophrenia. Low PEA is associated with difficultypaying attention or thinking clearly, and in depression.

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Neurotransmitter Levels

Neurotransmitter levels can now be determined by a simple and convenient urine testcollected at home. Knowing your neurotransmitter levels can help you correct a problemtoday or prevent problems from occuring in the future.

For many years, it has been known in medicine that low levels of theseneurotransmitters can cause many diseases and illnesses. A Neurotransmitterimbalance can cause:

Depression Anxiety Attention deficit/ADHD Panic Attacks Insomnia Irritable bowel

PMS/ Hormone dysfunction Fibromyalgia Obesity Eating disorders Obsessions and Compulsions Adrenal dysfunction Psychosis Early Death Chronic Pain Migraine Headaches

What causes a neurotransmitter imbalance?

Prolonged periods of stress can deplete neurotransmitters levels. Our fast paced, fastfood society greatly contributes to these imbalances.