4 octobre 2015 par maty185
The autonomic nervous system (ANS) : https://en.wikipedia.org/wiki/Autonomic_nervous_system
Le système nerveux autonome ou système nerveux viscéral (aussi appelé système nerveux (neuro-)végétatif) : https://fr.wikipedia.org/wiki/Syst%C3%A8me_nerveux_autonome
The sympathetic ganglion: https://en.wikipedia.org/wiki/Sympathetic_ganglion
The sympathetic nervous system:
Le système nerveux sympathique ou système nerveux orthosympathique: https://fr.wikipedia.org/wiki/Syst%C3%A8me_nerveux_sympathique
Parasympathetic ganglion: https://en.wikipedia.org/wiki/Parasympathetic_ganglion
Parasympathetic nervous system: https://en.wikipedia.org/wiki/Category:Parasympathetic_nervous_system
Norepinephrine ( Noradrenaline ) : https://en.wikipedia.org/wiki/Norepinephrine
La Noradrénaline ( Norépinéphrine ) : https://fr.wikipedia.org/wiki/Noradr%C3%A9naline
Above: Schema of some pathways in the formation, release, and metabolism of noradrenaline (norepinephrine) from sympathetic nerve terminals. Tyrosine is converted into dihydroxyphenylalanine (dopa) by tyrosine hydroxylase (TH). Dopa is converted into dopamine (DA) by dopa decarboxylase (DDC). In the vesicles, dopamine is converted into noradrenaline (NA) by dopamine β-hydroxylase. Nerve impulses release both dopamine β-hydroxylase and noradrenaline into the synaptic cleft by exocytosis. Noradrenaline acts predominantly on α1-adrenoceptors but has actions on β-adrenoceptors on the effector cell of target organs. It also has presynaptic adrenoceptor effects. Those acting on α2-adrenoceptors inhibit noradrenaline release and those on β-adrenoceptors stimulate noradrenaline release. Noradrenaline may be taken up by a neuronal process (uptake 1) into the cytosol, where it may inhibit further formation of dopa through the rate-limiting enzyme tyrosine hydroxylase. Noradrenaline may be taken into vesicles or metabolized by monoamine oxidase (MAO) in the mitochondria. Noradrenaline may be taken up by a higher-capacity, but lower-affinity, extraneuronal process (uptake 2) into peripheral tissues, such as vascular and cardiac muscle and certain glands. Noradrenaline is also metabolized by catechol-O-methyl transferase (COMT). Thus, noradrenaline measured in plasma is the overspill not affected by these numerous processes. (b) Outline of the major transmitters at autonomic ganglia and postganglionic sites on target organs supplied by the parasympathetic and sympathetic efferent pathways. The acetylcholine (ACh) receptor at all ganglia is of the nicotinic subtype (ACh-n). Ganglionic blockers such as hexamethonium thus prevent both parasympathetic and sympathetic activation. Atropine, however, acts only on the muscarinic (ACh-m) receptors at postganglionic parasympathetic and sympathetic cholinergic sites. The cotransmitters, along with the primary transmitters, are also indicated. NPY, neuropeptide Y; VIP, vasoactive intestinal peptide.
There are differences between organs, especially the gastrointestinal system, in which the enteric nervous system is considered as a third autonomic division. The multiplicity of neural pathways, transmitters, and modulators results in selective control of responses in specific vascular territories and organs, making it a highly complex but precisely regulated and integrated system.
Effect of aspartame on the brain
Aspartame is composed of:
Effects of phenylalanine
- reduction of dopamine
- reduction of serotonin
Phenylalanine not only plays a role in amino acid metabolism and protein structuring in all tissues, but is also a precursor for tyrosine, DOPA, dopamine, norepinephrine, epinephrine, phenylethylamine and phenylacetate. Phenylalanine also plays an important role in neurotransmitter regulation.
Pathways of uptake in the body
– A part is converted into tyrosine (a nonessential amino acid) in the liver by the enzyme phenylalanine hydroxylase. Tyrosine is converted into dihydroxyphenylalanine (DOPA) once it is in the brain, by the enzyme tyrosine hydroxylase, with the help of the co-factors oxygen, iron and tetrahydrobiopterin (THB). Dopamine, a catecholamine, is formed from DOPA by an aromatic amino acid decarboxylase. Tyrosine hydroxylase activity is inhibited by high concentrations of dopamine through its influence on the THB co-factor (negative feedback). This system is very necessary to prevent large amount of dopamine being produced, as dopamine is an inhibitory neurotransmitter.
– The remaining portion of phenylalanine (not converted in the liver) will bind to a large neutral amino acid transporter (NAAT) to be carried over the blood–brain barrier (BBB). NAAT is also a co-transporter for phenylalanine, tryptophan (an important precursor for synthesis of serotonin), methionine and the branch-chained amino acids, so a large quantity of one amino acid in the blood stream will occupy most of this transporter.
Reduction of dopamine
If high concentration of aspartame is taken through the daily diet, 50% of it is broken down to phenylalanine. If phenylalanine competes with tyrosine for NAAT, it will bind more frequently and freely than tyrosine owing to its higher concentration, and thus lead to lower concentrations of dopamine in the brain.
This causes reduced dopamine and serotonin production as the enzyme actions controlling numerous types of neurotransmitters (and their precursor amino acids) are debilitated by overdoses of the competitive circulating phenylalanine isolates
Reduction of serotonin
Serotonin, an indolamine, causes powerful smooth muscle contraction. Physiologically, it is also important for behaviour and control of sleep, temperature, appetite and neuroendocrine functions. Tryptophan, independently utilized for synthesis of serotonin in the brain, is transported across the BBB via NAAT. Therefore, if NAAT is occupied with phenylalanine, tryptophan will not be adequately carried across the BBB and serotonin production can ultimately be compromised.
Effects of aspartic acid
Aspartic acid is thought to play a role as an excitatory neurotransmitter in the central nervous system. Glutamate, asparagines and glutamine are formed from their precursor, aspartic acid. Aspartate is inactivated by reabsorption into the presynaptic membrane and it opens an ion channel. Aspartate is an excitatory neurotransmitter and has an increased likelihood for depolarization of the postsynaptic membrane. Even short-lived increases of a powerful neural stimulator are enough to induce neuroendocrine disturbances.
Effect of methanol
The methanol in the body is converted to formate, which is then excreted. It can also give rise to formaldehyde, diketopiperazine (a carcinogen) and a number of other highly toxic derivatives. The absorption-metabolism sequence of methanol-formaldehyde- formic acid also results in synergistic damage. The accumulation of formate rather than methanol is itself considered to cause methanol toxicity, but research has shown that formaldehyde adducts accumulate in the tissues, in both proteins and nucleic acids, after aspartame ingestion (Trocho et al., 1998). The formed adducts of the metabolic poisons alter both mitochondrial DNA and nucleic DNA. Methanol and formaldehyde are also known to be carcinogenic and mutagenic. The damaged DNA could cause the cell to function inadequately or have an unbalanced homoeostasis, thus initiating disease states. In addition, it is thought that the methanol is the aspartame is converted to formaldehyde in the retina of the eye, causing blindness.
Effects of aspartame on the blood brain barrier
A compromised BBB (altered lipid-mediated transport or active carrier transport) will result in the transport of excitotoxins (aspartame) across BBB and within the cerebrospinal fluid causing several adverse reactions to occur:
- The nerves will be stimulated to fire excessively by the excitotoxins.
- The offset of induced, repeated firing of the neurons mentioned above will require normal enzymes, which are negated by the phenylalanine and aspartic acid present in aspartame.
These compulsory enzyme reactions mentioned above require a normal functioning energy system. Thus, it could be stated that the neurons become compromised from:
- diminishing intracellular ATP stores;
- the presence of formaldehyde;
- intracellular calcium uptake been changed (e.g. phenylalanine binds to NMDA receptor, not glutamate, thus altering calcium channels);
- cellular mitochondrial damage;
- destruction of the cellular wall; and
- subsequent release of free radicals.
These preceding reactions potentiate oxidative stress and neurodegeneration.
Secondary damage is caused by the toxic by-products, which in turn will increase capillary permeability, continuing to destroy the surrounding nerve and glial cells, thus further obstructing enzyme reactions and promoting DNA structural defects. Cellular death occurs over the next 1–12 h.
For more information see:
Direct and indirect cellular effects of aspartame on the brain.
Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies.
Berardi Daniela (matr. 300429) e Coppo Alessandra (matr. 276329 27)
Scuola di Specializzazione in Patologia Clinica 2° Anno
It was seen that aspartame disturbs amino acid metabolism, protein structure and metabolism, integrity of nucleic acids, neuronal function, endocrine balances and changes in the brain concentrations of catecholamines. It was also reported that aspartame and its breakdown products cause nerves to fire excessively, which indirectly causes a very high rate of neuron depolarization. The energy systems for certain required enzyme reactions become compromised, thus indirectly leading to the inability of enzymes to function optimally. The ATP stores in the cells are depleted, indicating that low concentrations of glucose are present in the cells, and this in turn will indirectly decrease the synthesis of acetylcholine, glutamate and GABA. The intracellular calcium uptake has been altered, thus the functioning of glutamate as an excitatory neurotransmitter is inhibited. Mitochondria are damaged, which could lead to apoptosis of cells and infertility in men and also a lowered rate of oxidative metabolism are present, thus lowering concentrations of the transmitters glutamate and production of GABA. The cellular walls are destroyed; thus, the cells (endothelium of the capillaries) are more permeable, leading to a compromised BBB. Thus, overall oxidative stress and neurodegeneration are present.
From all the adverse effects caused by this product, it is suggested that serious further testing and research be undertaken to eliminate any and all controversies surrounding this product.