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The main aim of drug therapy for this disease is to replace the deficiency of the transmitter (dopamine) in the basal ganglia (target of nigrostriatal projection). Another potentially useful but controversial approach is to implant fetal midbrain or adrenal medullary tissue into the deteriorating caudate nucleus and putamen. Dopaminergic projections from the ventral tegmental area to the limbic structures, especially the projections to nucleus accumbens, may be involved in emotional reinforcement and motivation associated with cocaine drug addiction. Epinephrine thus formed in the cytoplasm is actively transported back into storage vesicles in the nerve terminal (or chromaffin granules in the adrenal medulla) and stored for subsequent release. Antibodies, developed for enzymes involved in the synthesis of different catecholamine neurotransmitters, have been used for immunohistochemical identification of these neurons. After its release, serotonin is removed from the synaptic cleft by the mechanisms of reuptake and metabolism. The threat of their sting is what makes them unwelcome when they nest on, in or near peoples' homes. Research done through Tufts University Framingham Offspring Study has suggested that 40% of people between the ages of 26 and 83 have low-normal plasma B12 levels.
The absorption, assimilation and methylation of B12 is a very complex process and there are many factors that reduce our bodies ability. Without adequate methylation processes the individual cannot adapt or heal effectively and will suffer the delirious effects of accelerated aging (5). Individuals with gene mutations such as MTHFR or MTRR have trouble with the process of methylating B12.
The best sources of B12 are found in organic meat and eggs.  Be sure to find humanely raised, grass-fed sources of these meat products.
Health practitioners trained in functional medicine will see slight elevations in MCV, MCH and MCHC and be suspicious of functional methylation issues.
When people have MTHFR gene mutations, in particular a homozygous trait, they require more B12, folate, and B6 for their detoxification pathways and body to function optimally. It’s estimated that those with one mutation (heterozygous) decrease their ability to methylate by 30% and those with two mutations (homozygous) decrease their ability to methylate by 70%, making it virtually impossible get adequate B12 from diet alone (19).
This is a very common test that I use to look at methylation factors, nutrient deficiencies, detox pathways and neurotransmitter function.
There are several different forms of B12 including cyanocobalamin (Cyano-B12), Methylcobalamin (Methyl B12), Hyroxocobalamin (Hydroxy-B12) and Adenosylcobalamin (Adeno-B12). This form is naturally created by bacteria fermentation and is the main type that is found in food. This is the least stable form of B12 outside of the human body and therefore is not recommended in supplement form. Zittan E, Preis M, Asmir I, Cassel A, Lindenfeld N, Alroy S, Halon DA, Lewis BS, Shiran A, Schliamser JE, Flugelman MY. Shibuya K, Misawa S, Nasu S, Sekiguchi Y, Beppu M, Iwai Y, Mitsuma S, Isose S, Arimura K, Kaji R, Kuwabara S.
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Because dopamine does not cross the blood-brain barrier, its immediate metabolic precursor (L-DOPA, or levo-dopa), which does cross this barrier, is administered orally.
A future possibility is transplantation of genetically engineered cells capable of expressing tyrosine hydroxylase that is involved in the synthesis of dopamine.
Many adult psychotic disorders, including schizophrenia, are believed to involve increased activity at dopaminergic synapses. Cocaine (a local anesthetic drug) blocks the reuptake of dopamine (and norepinephrine) into the nerve terminals.
Initial steps in the synthesis of norepinephrine (up to the step of transport and storage of dopamine into the storage vesicles) are described in the section about dopamine.


Activation of presynap-tic adrenergic receptors results in inhibition of the release of norepinephrine. Norepinephrine is released as a transmitter from postganglionic sympathetic nerve terminals.
The initial steps (up to synthesis and storage of norepinephrine in the storage vesicles) in the synthesis of epinephrine are identical to those of nore-pinephrine.
The mechanisms for removal of epinephrine are the same as those for norepinephrine and dopamine. Two major groups of adrenergic cells have been identified in the medulla: C1 neurons located in the rostral ventrolateral medulla, and C2 neurons located in the solitary nucleus and tract (nucleus tractus solitarius).
For example, positive staining for tyrosine hydroxylase indicates that the neuron contains a catecholamine.
Indole consists of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. The distribution of some 5-HT receptors on different components of the serotonergic synapse is also shown. Reuptake involves entry of serotonin into the neuronal terminals by active transport via plasma membrane serotonin transporter proteins (SERT). Serotonin-containing neurons have been identified in the midline raphe nuclei of the medulla, pons, and upper brainstem.
Serotonin-containing cells in the raphe regions of the brainstem are believed to play a role in descending pain-control systems. Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitors (SSRIs) are used in the treatment of depression, anxiety disorders, and some personality disorders. Their paper-like nests are usually ball-shaped and can be in the ground, in walls or hanging from trees or buildings. It’s entirely possible that at least some of the symptoms we attribute to “normal” aging – such as memory loss, cognitive decline, decreased mobility, etc. Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy. Pseudovitamin B(12) is the predominant cobamide of an algal health food, spirulina tablets.
Diagnostic value of the mean corpuscular volume in the detection of vitamin B12 deficiency. High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia. Homocysteine and methylmalonic acid as indicators of folate and vitamin B12 deficiency in pregnancy.
Absorption of cyanocobalamin, coenzyme B 12 , methylcobalamin, and hydroxocobalamin at different dose levels. L-DOPA is transported into the brain via a large neutral amino acid transporter, and it permeates the striatal tissue, where it is decarboxylated to dopamine. Elevated levels of dopamine in certain brain circuits may be responsible for the euphoric effects of cocaine. The noradrenergic neurons contain an enzyme, dopamine b-hydroxylase (DBH), which converts dopamine into norepinephrine. These neurons send projections through the central tegmental tract and the medial forebrain bundle to the thalamus, hypothalamus, limbic forebrain structures (cingulate and parahippocampal gyri, hippocampal formation, and amygdaloid complex), and the cerebral cortex.
Positive staining for tyrosine hydroxy-lase, but not DBH, indicates that the neuron contains dopamine. Metabolism involves deamination of serotonin by MAO to form 5-hydroxyindoleacetaldehyde, which is then oxidized by aldehyde dehydrogenase to form 5-hydroxyindoleacetic acid.
The raphe nuclei are located in the central portion of the medullary, pontine, and midbrain reticular formation.


Other serotonin-containing neurons may play a role in mediating affective processes, such as aggressive behavior and arousal. These drugs inhibit reuptake of serotonin into the presynaptic terminal and increase the extracellular level of the serotonin available for binding to the postsynaptic receptor. Each bee can sting only once as its stinger is left in the wound and the bees disembowel themselves when they pull away from you.
They usually nest underground but are also frequently found in compost piles and sometimes in walls. In recent years, a combination of L-DOPA and carbidopa (Sinemet) has been prescribed for this disease. This mechanism is not responsible for the local anesthetic effect of cocaine that is mediated via the blockade of neuronal voltage-gated Na+ channels.
It should be noted that the synthesis of norepinephrine takes place in the storage vesicles (Fig.
8-13), norepinephrine stored in the vesicles leaks out into the cytoplasm and is converted into epinephrine by the enzyme phenylethanolamine-N-methyl-transferase (PNMT). Positive staining for DBH, but not PNMT, indicates that the neuron contains norepinephrine.
Serotonin synthesized in the pineal gland serves as a precursor for the synthesis of melatonin, which is a neurohor-mone involved in regulating sleep patterns. For example, fluoxetine (Prozac) selectively blocks reuptake of serotonin and enhances serotonin levels in the brain. These hornets are very aggressive when their nest is approached or disturbed but rarely bother people at other times. Dopaminergic neurons located in the substantia nigra are degenerated in this disease, and the release of dopamine in the caudate nucleus and putamen is decreased. Carbidopa is an inhibitor of dopa-decarboxylase and reduces the decarboxylation of L-DOPA in the peripheral tissues, enabling a greater concentration of this precursor to reach the brain. It may produce beneficial effects in mental depression via enhancement of transmission through 5-HT1A receptors.
Toxic effects of these drugs are dehydration, hyperthermia, tachycardia (increase in heart rate), and sweating. When they sting you a chemical is released which tells the other wasps to come and sting you too!
The exact mechanism by which increased levels of norepinephrine in the CNS mediate the antidepressant action of these drugs is not clearly known.
Plasma tryptophan enters the brain by an active uptake process and is hydroxylated by tryptophan hydroxylase to form 5-hydroxytryptophan, which is immediately decarboxylated by aromatic L-amino acid decar-boxylase to form serotonin. Undesirable side effects following prolonged use of Ecstasy are believed to be caused by the degeneration of the projections of serotonin-containing neurons. Norepinephrine released into the synaptic cleft is removed by the mechanisms described in the dopamine section. Serotonin is then actively taken up via vesicular monoamine transporter and stored in vesicles where it is ready for release. It is a vasoconstrictor of intracra-nial arteries and has proved useful in treating migraine headaches. Projections from the raphe nuclei terminating in the dorsal horn regulate the release of enkephalins.
Sumatriptan-induced constriction of intracra-nial arteries is mediated via 5-HT1B 5-HT1D receptors that are located in the smooth muscle and endothelial cells of these arteries.



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