Complexity of dopamine metabolism - PubMed Central (PMC)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693914
May 17, 2013 · A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates reactive oxygen species (ROS) and DA oxidation can lead to endogenous neurotoxins whereas some DA derivatives show antioxidative effects.
tyrosine or phenylalanine
DA biosynthesis and degradation. The major pathway for DA biosynthesis starts at tyrosine or phenylalanine which can be hydroxylated by phenylalanine hydroxylase. Tyrosine is hydroxylated to form DOPA, now bearing the catechol moiety, by BH4-dependent tyrosine hydroxylase or alternatively by tyrosinase. Decarboxylation of DOPA by AADC leads then to DA. In another pathway for DA synthesis AADC action occurs before the hydroxylation at the aromatic ring. Tyramine is then oxidized by Cyp2D. Besides being a neurotransmitter itself, DA is also the precursor of epinephrine and norepinephrine. DA degradation is performed by COMT, MAO, ADH, ALDH and AR in variable order leading to DOPAC and HVA as the main endproducts. Phenolsulfotransferases and uridine diphosphoglucuronosyltransferases catalyze conjugation reactions with phosphate and glucuronic acid respectively. The relative contributions of the different enzymes are strongly species-, tissue- and celltype-dependent. The depicted reactions may occur in distinct compartments.
Cocaethylene Synthesis and Pathophysiology - Proteopedia, life in 3D
http://proteopedia.org/wiki/index.php/Cocaethylene_Synthesis_and_Pathophysiology
Complexity of dopamine metabolism - PubMed Central (PMC)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693914
May 17, 2013 · A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates reactive oxygen species (ROS) and DA oxidation can lead to endogenous neurotoxins whereas some DA derivatives show antioxidative effects.
Cited by: 309
Publish Year: 2013
Author: Johannes Meiser, Daniel Weindl, Karsten Hiller
Complexity of dopamine metabolism | Cell Communication and ...
https://biosignaling.biomedcentral.com/articles/10.1186/1478-811X-11-34
May 17, 2013 · A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates reactive oxygen species (ROS) and DA oxidation can lead to endogenous neurotoxins whereas some DA derivatives show antioxidative effects.
Dopamine Receptors and Neurodegeneration
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567218
Oct 01, 2015 · Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D 1 and D 5 ) and the D2-like (D 2 , D 3 and D 4).
Cited by: 108
Publish Year: 2015
Author: Claudia Rangel-Barajas, Israel Coronel, Benjamín Fl
DEFINITION Schizophrenia (see also here) is a debilitating chronic psychiatric syndrome that affects 1% of the adult population, characterized by a course of more than six months and the persistence of abnormal thinking, behavior, and emotions.
The term actually means a class of disorders that vary in severity and progression. The etiology is complex (genetic, morphological, environmental, social ...) and still unclear.
EPIDEMIOLOGY
Schizophrenia is a disorder that occurs most frequently in adults aged 15 to 25 years.
The prevalence in the general population is about 1%. The prevalence among first-degree relatives of people affected is: 5-12%; there is a concordance of 50-65% among monozygotic twins; while in dizygotic twins it is equal to 5-12%.
The disease tends to occur earlier in males than in females. In females the event is late: usually around 30-35 years. The late-onset forms are generally better prognosis because they present a predominance of positive symptoms (and therefore a better response to drug therapy) and a minor frequency of disorganization and negative symptoms. There is also a greater preservation of: basic personality, affect and social functioning.
SYMPTOMS
There are three clinical phases :
• Premorbid
• Prodromal
• Overt disease (active phase or state period)
The Premorbid Phase
The vulnerability of schizophrenia may be evident before the onset of a disease in the form of a premorbid and inadequate functioning: 50% of future schizophrenics do not have a particular premorbid personality; 25% non-specific traits (emotional sensitivity, difficulty in keeping with the others, etc.); the remaining 25%, represented mainly by children of parents with schizophrenia, presents premorbid personality characterized by introversion, isolation or withdrawal, distrust, poor social skills, mild cognitive impairment (attentional, poor arithmetic skills), weird and eccentric behavior, pseudo-depressive aspects with disregard for the usual activities carried out by coetaneous (sports, the opposite sex), poor ability to emotionally connect, irrelevant psychomotor abnormalities (neurological soft sign), interest-philosophical-religious-esoteric astrology.
The Prodromal Phase
In the next phase , there is a change from the status of previous operation, often after a normal event experienced as stressful by the subject (exams, university, military, separations and losses). This implies the development of subclinical signs and symptoms that signal the imminent failure occurring before the onset of the disease (differential diagnosis with adolescent adjustment disorder). This trend may have:
Acute phase (in days or weeks) with a feeling of sudden break with the past and positive rapid onset of classic symptoms.
Slow, insidious and subtle (in months or years) with progressive change in the way of being, usually in the earlier onset forms (which are the most disabling clinical course).
At this stage what occurs is:
Emotional detachment with reduced expression of the emotions (affective coarctation) and flattening of affective relationships.
Progressive difficulty in relation to isolation and social withdrawal (you leave school, friends, sports, hobbies and closed in a room or walking endlessly and aimlessly).
Loss of interest motivation with the appearance of interests sometimes strange and magical themes of eccentric, pseudo-philosophical or pseudo-faced with an obvious lack of critical.
Strange behavior / eccentric or impulsive, irritability (unprovoked aggression towards family, food, or inappropriate sexual behaviors).
Impoverishment of the ideational content and the appearance of bizarre ways of thinking .
Reduced social functioning and personal hygiene.
Inability to perform peculiar tasks of their role.
Progressive decline in attention, concentration, distractibility, impaired learning and performance at school and work.
Anxiety that evolve in a vague sense of unease and fear in deep anguish.
Perplexity
The Active Phase
In overt disease (active phase or period of state) there have been found positive symptoms, negative and disorganization variously associated.
Schizophrenia is characterized by two types of symptoms:
Positive symptoms
Negative Symptoms
Positive symptoms can be included under the term psychosis.
They are characterized by: obsessions, delusions, hallucinations and thought disorder.
Negative symptoms include a decline or disappearance of some of the skills of the person (emotional detachment, poverty of speech, decreased functions of communication, lack of motivation).
DIAGNOSIS
The diagnosis of schizophrenia requires the fulfillment of the following criteria:
A- (Symptoms and signs) The persistent presence of two or more of the following symptoms for a significant period of time that is considered at least a month (it appears that the duration may be less if the problem recedes following treatment):
Delusions
Hallucinations
Disruption of verbal discourse (eg. losing the thread, incoherence, digression and expression are too abstract)
Severe disorganization of behavior (eg. in clothing, diurnal habits, sleep disturbances, dysphoria, laugh or cry frequently and inappropriately), or been severely catatonic.
Presence of negative symptoms, that convey a strong sense of disinterest, distance or absence of the subject: affective flattening (lack or strong reduction of emotional responses), alogia , avolizione (lack of motivation), attention deficit disorder and intellectual capacity, lack of eye contact.
B- Deficits or social dysfunction and / or employment: For a significant period of time one or more major areas of the subject's life are in serious jeopardy than before the onset of the disorder (work, interpersonal relationships, body care, nutrition, etc..)
C- Duration: persistence of symptoms "B" for at least six months, including at least a month of persistent symptoms of "A".
Note: The fulfillment of the criterion A is the only required (eg. the diagnosis is not required for the fulfillment of points B and C) only if the fixed ideas are bizarre and unrealistic, if hallucinations consist of hearing two or more unreal voices that speak to each other, or hearing a voice that "says" live the actions and perceptions of the patient.
DIAGNOSTIC PROCEDURES OF FUNCTIONAL NEUROIMAGINING
The Functional Neuroimaging is the use of neuroimaging technology to measure brain metabolism, in order to analyze and study the relationship between the activity of certain specific brain areas and brain functions.
The most commonly used methods include positron emission tomography (PET), functional magnetic resonance (fMRI), the multichannel EEG (EEG), the Single-photon emission computed tomography (SPECT), the magnetoencephalography (MEG) and the infrared spectroscopy (NIRS).
PET, fMRI, NIRS and SPECT measure changes in blood flow, related to the increase of cellular activity and thus neuronal activity. These changes in flow regions are defined as "active". The areas of the brain that are activated when the subject performs a particular task play a key role in the understanding of behavior, emotions, cognitive function and neural substrate.
The technique to observe the areas activated during a particular task requires multiple scans of brain activity. Activity is detected primarily "at rest", ie in the context of experimental research, but without the specific task. Next activity is detected during the task. The difference between the two maps can identify areas activated specifically during that particular task.
MEG and EEG record neural activity directly in the form of electromagnetic radiation, instead of PET images, SPECT and fMRI images that return indirect neuronal activity (for example, by studying in SPECT cerebral blood flow).
LABORATORY TEST
Lab tests may help to highlight the physical processes that underlie the patient's symptoms. The tests currently in use include various techniques for the representation of the brain, blood and urine tests, and analysis of the endocrine function of neurotransmitters and the use of EEG to evaluate the electrical activity of the brain.
NEUROCHEMICAL TESTS
Dexamethasone-suppression test
5-HIAA excreation test
ETIOLOGY and PATHOGENESIS
There is no single cause that leads to the occurrence of this disease. It would seem to be involved:
Alterations in neurotransmission
Morphologic modifications(investigated by diagnostic imaging and parallel with the theory of fractals)
Risk factors
1. ALTERATIONS IN NEUROTRANSMISSION
The dopamine theory is among the hypotheses of the pathophysiological causes of schizophrenia.
Dopaminergic hypotheses
The symptoms of schizophrenia are due to hyperactivity of the dopaminergic system, especially in its mesolimbic component at post synaptic.
Dopaminergic system
The dopamine system is composed of three main ways:
Nigrostriatal Pathway, important in motor control
Mesolimbic and mesocortical pathway that originates from clusters of midbrain cells to reach parts of the limbic system, especially the nucleus accumbens, and cortex. It is member of the control of behavior.
The tuberoinfundibular pathway and pituitary pathway used for the endocrine control.
The main neurotransmitter in this system is the dopamine, a noradrenaline precursor that works on five different subclasses of receptors:
D1 e D5 : involved in the stimulation of the adenylate cyclase
D2, D3 e D4 : involved in the inhibition of the adenylate cyclase
The receptors D1 and D2 (pre and post-sinaptic) are involved in the modulation of psychomotor systems , while in the schizophrenia the activation of these receptors causes hallucinations, delusions, paranoia (positive symptoms).
The receptors D3 and D4 are located most of all in areas mainly involved in the origin of the schizophrenia negative symptoms.
Evidence of this hypothesis is:
L-DOPA worsen symptoms in schizophrenic patients; it may lead to onset of hallucinations in patients with Parkinson
The DA receptor antagonists are effective in the treatment of schizophrenia.
It is possible to observe increased levels of DA and HVA (homovanillic acid) in the striatum and cortex of schizophrenic patients (post-mortem)
It is possible to observe an increase of DA D2 receptors in striatal and limbic brain of schizophrenics (post-mortem)
PET Studies in vivo show, with some variability, an increase of D2 receptors in the brains of schizophrenics and an increase of DA release in response to apomorphine compared to controls.
However, other neurotransmitter systems seem to be involved In schizophrenia,:
Serotonergic system :Serotonin inhibits the firing of dopaminergic neurons in striatal and mesolimbic level.
Noradrenergic and gabaergic systems
Cotrasmitter and neuro peptides: cholecystokinin, which is located in the dopaminergic neurons of the mesolimbic system and the Nerve growth factor which has recently been implicated as important cofactor in the mechanisms leading to this disease.
Glutamatergic system : less neurotransmitter release in schizophrenic patients.
2. MORPHOLOGIC MODIFICATIONS
Through the observation of magnetic resonance imaging studies of schizophrenic patients, it has been possible to observe brain abnormalities.
These changes include:
Expansion of the lateral ventricles (reported by 80% of studies)
Expansion of the third ventricle (73% of studies)
Involvement of the medial temporal lobe structures (74% of studies) such as the amygdala, hippocampus, parahippocampus around and neocortical temporal lobe regions.
If studies evaluating both the white matter and the gray matter are taken into consideration, in the temporal superior circle, abnormalities can be highlighted in 67% of the cases.
It Has also been reported evidence of abnormal frontal lobe (59% of studies), particularly the prefrontal gray matter and orbitofrontal regions in frontal and subcortical abnormalities.
These abnormalities seem to cause a disturbance in the connection between the various regions of the brain inside these regions. This is probably originated in the course of neurodevelopment.
Several theories have been proposed in the attempt to understand the implication of so many brain regions in schizophrenia, many of which are functionally related to each other.
Some researchers have hypothesized that abnormalities in the thalamus and its connections with the cortex and the cerebellum can cause a sort of cognitive dysmetria .
Others have focused their attention on the frontal lobes, basal ganglia and connections with the temporal lobe.
In contrast to the hypothesis that schizophrenia may be considered a neurodevelopmental encephalopathy, it has been proposed a model of disconnection in order to explain how changes in the temporal lobe may interrupt the connections between the limbic and prefrontal regions of the temporo-and vice versa.
A New Frontier: the Fractals
The fractal dimension (FD) was used to highlight the findings of brain structural irregularities in schizophrenic patients. This new approach seems to be a useful way to quantify the complexity of the bound form cerebral convolutions of the human brain.
But what is meant by fractal dimension?
A fractal is a geometric object that is repeated in its structure the same on different scales, this means that changes appearance even when viewed through a magnifying glass. There is a wide variety of objects that are defined but each manifests fractal variables. It 'so good to have these common characteristics of these objects.
Nature produces many examples of shapes very similar to fractals. For example, in a tree (especially in spruces) each branch is roughly similar to the entire tree and each branch in turn is similar to their own branch, and so on. It is also possible to see phenomena of self-similarity in the shape of a coast : with even larger satellite images, you can see that the general structure of more or less indented bays shows many components that, if not identical to the original, they look pretty much the same. According to Mandelbrot, the relationship between fractals and nature are deeper than you think.
« They believe that, in some way or the other, fractals have connections with the structure of the human mind. It is for this very reason that people find them so familiar. This familiarity still remains a mistery and the more they delve into this topic, the more the mistery increases. »
Benoit Mandelbrot
Fractals are used to find a new representation that starts from the basic idea that the small in nature is nothing but a copy of the great. Several mathematicians and physicians, observing and studying the physiology of the human body, found the structures and geometric forms of fractal figures and were able to apply everything that has been presented so far, to organs, tissues and cells.
A significant example of fractal theory applied to biology is the neuronal structure.
Neurons are cells used for the collection and transfer of information from all parts of our body in the form of electrical impulses. These signals are collected by means of thin cytoplasmic extensions, called dendrites, which then transfer them to the cell body. Information can be sent to adjacent neurons and move it throughout the body to reach the affected area. The fractal approach of these cells is clear by looking at the dendrites at high magnification level: on the larger ramifications there are other smaller.
The fractal dimension can serve the classification of neurons based on morphological characteristics of the branches. Starting from some basic parameters, it is possible to start the analysis of fractal geometry applied to a given cell of the organism, a tissue or to a specific organ. With regard to nerve cells, their functions are largely dependent on its structure. To understand how a neuron integrates synaptic thousands of points, in order to generate an appropriate response, it requires the complete knowledge of geometry and cell morphology.
You can forward this brief classification:
There are biological fractal structures beyond a certain point pass into a new shape and functions of different fractal (trachea and bronchial tree).
There are fractal isolated biological structures, but which are linked to a higher-order fractal (many types of neurons of the cerebral convolutions with the macroscopic system. An example of these neurons are the Purkinje cells with their dendrites which are characteristic of fractal structures because the main branches are divided into small extensions to scalar relationships, consistent with each other.)
Isolated biological structures fractals (bird feathers)
Through the observation of MR images from patients with schizophrenia compared to healthy controls, it was found the FD (fractal dimension), taking into account the following parameters according to some mathematical methods that take into consideration the ratio of gray matter / white matter, total cranial volume, relief morpho - structural each hemisphere.
The results have shown that schizophrenics have larger values of FD compared with healthy controls, in relation to the total cranial volume and in reference to the right hemisphere.
3. RISK FACTORS
Genetic Factors
Several genes are involved in the pathogenesis of schizophrenia, but nobody has an important role so as to be recognized as the only candidate gene.
Among the possible genes involved, studies have been conducted on:
Gene COMT (Aggressive behavior in schizophrenia is associated with the low enzyme activity COMT polymorphism: a replication study.2003) (catechol-O- methyltransferasi) : helps the catecolaminic neurotransmitter metabolism, such as dopamine.
Gene WKl1 (Is the WKL1 gene associated with schizophrenia?.2004) at the level of chromosome 22. It codifies a proteine for the transportation of alternate current along the neurons. This protein is found exclusively in the brain.
Gene PLCB1 (Deletion of PLCB1 gene in schizophrenia affected patients.2011): found in chomosome 20. In patients affected by schizophrenia there is a deletion of this gene at the level of the frontal cortex.
Genes DOCK4 e CEACAM21 (DOCK4 and CEACAM21 as novel schizophrenia candidate genes in the Jewish population.2011)
Environment and Social Factors
There are several theories that are based on the concept of conflict and disharmony within the family as a contributory cause of schizophrenia.
THERAPY
Today you can get complete remissions by the critical phases and significant improvement of cognitive, affective and relational in the residual phases.
You can also start early treatment with a significantly lower risk of developing the disorder.
The main treatments for schizophrenia are called antipsychotics. Antipsychotics help
treating the positive symptoms of schizophrenia, helping to correct an imbalance in chemical reactions allow brain cells to communicate with each other.
As is the case for drug treatments for other illnesses, many patients with serious mental illness need to try several before finding an antipsychotic drug, or combination of medications, that works best for them.
The Conventional Antipsychotics were introduced in the 50s and all had the same ability to treating the positive symptoms of schizophrenia. Most of these early antipsychotics "conventional" products differed in side effects. These conventional antipsychotics include:
» chlorpromazine (Thorazine)
» fluphenazine (Anatensol, Moditen)
» haloperidol (Haldol)
» trifluoperazine (Modalina)
» perphenazine (Trilafon)
» thioridazine (Mellaril)
The new "atypical" antipsychotics. Over the past ten years have introduced new "atypical" antipsychotics. Compared to older antipsychotic "conventional", these drugs appear to be equally effective
in reducing positive symptoms such as hallucinations and delusions - but are they better in raising the negative symptoms of the disease, such as apathy, thinking problems, and lack of energy.
The atypical antipsychotics include:
» risperidone (Risperdal)
» clozapine (Clozaril)
» olanzapine (Zyprexa),
» quetiapine (Seroquel)
» ziprasidone (not yet commercially available in Italy)
The current treatment guidelines recommend the use of an atypical antipsychotic, clozapine, in part, as a first treatment option for new patients. Instead, for patients who already benefit from treatment with conventional antipsychotics, atypical with a replacement may not be the best choice. Those wishing to change their medication should always consult your health care work together to develop the treatment plan more effective and safe as possible.
The therapy also includes a psycho-social rehabilitation.
Research shows that people with schizophrenia who attend structured programs, psychosocial rehabilitation, and continue with medication, better manage the disease and getting a better quality of life.
What are the side effects of medications used to treat schizophrenia?
All medicines have side effects.
Different medications produce different side effects, and people differ in both quantity and severity of side effects they experience.
Side effects can be treated by changing the dose of medication, changing the type of medication or treating the side effects directly, by other medications.
The most common side effects of antipsychotic drugs are: dry mouth, constipation, blurred vision, drowsiness.
Some people experience sexual dysfunction or decreased sexual desire, changes in
menstrual cycle and significant weight gain. Other common side effects are related and motor problems. These side effects include: agitation, rigidity, tremors, muscle spasms, and one of the most unpleasant and serious side effects, a condition called tardive dyskinesia.
Tardive dyskinesia is a movement disorder, which occurs in uncontrolled facial movements and sometimes shooting or twisting movements of other body parts. This condition usually develops after several years of treatment with antipsychotic drugs, and to a greater extent in older adults. Tardive dyskinesia affects 15 to 20% of those treated with conventional antipsychotics. The risk of being affected by tardive dyskinesia is lower for those taking the newer antipsychotics. Tardive dyskinesia can be treated with other drugs or reducing the dosage of the antipsychotic, if possible.
Serena Del Peschio
AnnalisaSchizophrenia
http://flipper.diff.org/app/items/3651
A Standardized Chinese Herbal Decoction, Kai-Xin-San, Restores Decreased Levels of Neurotransmitters and Neurotrophic Factors in the Brain of Chronic Stress-Induced Depressive Rats
南京中医药大学
Kai-xin-san (KXS)开心散, a Chinese herbal decoction being prescribed by Sun Simiao in Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma, Polygalae Radix, Acori tatarinowii Rhizoma, and Poria. KXS has been used to treat stress-related psychiatric disease with the symptoms of depression and forgetfulness in ancient China until today. However, the mechanism of its antidepression action is still unknown. Here, the chronic mild-stress-(CMS-) induced depressive rats were applied in exploring the action mechanisms of KXS treatment. Daily intragastric administration of KXS for four weeks significantly alleviated the CMS-induced depressive symptoms displayed by enhanced sucrose consumption. In addition, the expressions of those molecular bio-markers relating to depression in rat brains were altered by the treatment of KXS. These KXS-regulated brain biomarkers included: (i) the levels of dopamine, norepinephrine, and serotonin (ii) the transcript levels of proteins relating to neurotransmitter metabolism; (iii) the transcript levels of neurotrophic factors and their receptors. The results suggested that the anti-depressant-like action of KXS might be mediated by an increase of neurotransmitters and expression of neurotrophic factors and its corresponding receptors in the brain. Thus, KXS could serve as alternative medicine, or health food supplement, for patients suffering from depression.
(PDF) A Standardized Chinese Herbal Decoction, Kai-Xin-San, Restores Decreased Levels of Neurotransmitters and Neurotrophic Factors in the Brain of Chronic Stress-Induced Depressive Rats
https://www.researchgate.net/publication/230843993_A_Standardized_Chinese_Herbal_Decoction_Kai-Xin-San_Restores_Decreased_Levels_of_Neurotransmitters_and_Neurotrophic_Factors_in_the_Brain_of_Chronic_Stress-Induced_Depressive_Rats
单胺氧化酶
MAO是单胺降解的关键分子，也是许多治疗抑制剂(MAOI)的靶点。它以黄素腺嘌呤二核苷酸(FAD)为辅助因子，催化CAs的氧化脱氨反应生成相应的醛类，并生成过氧化氢作为副产物。有两种形式:MAO-A和MAO-B，它们由两个独立的基因编码[142,143]。酶定位于线粒体外膜，在中枢神经系统和外周均有发现。在中枢神经系统中，MAO存在于神经元、小胶质细胞和星形胶质细胞中。与其他神经元或胶质细胞相比，黑质神经元的MAO含量较低[144]。
两种酶的亲和力存在物种特异性差异:虽然两种MAO类型的体外亲和力相同，但DA在人体内主要被MAO- b氧化，在大鼠体内主要被MAO- a氧化[89]。然而，在大鼠和灵长类动物中，一种引起类pd症状的合成化合物MPTP[145]被MAO-B氧化[146]。The Dopamine Hypothesis of Schizophrenia - Advances in Neurobiology
https://psychscenehub.com/psychinsights/the-dopamine-hypothesis-of-schizophrenia/
Complexity of dopamine metabolism | Cell Communication and Signaling | Full Text
https://biosignaling.biomedcentral.com/articles/10.1186/1478-811X-11-34
Beef: Various types of beef will provide you with enough tyrosine increase dopamine levels.
Cheese: Eating cheese can provide you with the amino acid tyrosine, which helps you create dopamine. As an alternative to standard types of cheese, many people like to eat cottage cheese because it has lower fat.
Chicken: An ounce of breast meat chicken is estimated to contain nearly 1500 mg of tyrosine.
Eggs: If you eat eggs, you’re getting tyrosine. A raw, fresh egg white alone contains an estimated 1900 mg of tyrosine. Plus eggs provide the added benefit of choline, which is necessary for optimal neurotransmission.
Fish: You may want to consider eating fatty fish (particularly wild-caught fish) as a way to boost your dopamine levels. Fish contain omega-3 fatty acids (DHA and EPA) which have been shown to elevate dopamine levels in the brain. Examples of fish to consider include: halibut, salmon, striped bass, rainbow trout, tuna, and sardines. mackerel, salmon, striped bass, rainbow trout, halibut, tuna, and sardines.
Turkey: We’ve all heard that turkey contains tryptophan (a precursor to serotonin), but many people don’t know that it also contains sufficient tyrosine to increase dopamine.
Proteins are good stable sources of amino acids and will facilitate healthy dopamine levels in the brain. By eating some source of protein, you’ll be giving your brain some of the necessary amino acids to synthesize dopamine.
Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease
Elisa Greggio Elisabetta Bergantino Donald Carter Rili Ahmad Gertrude‐Emilia Costin Vincent J. Hearing Jordi Clarimon Andrew Singleton Johanna Eerola Olli Hellström
First published: 21 February 2005 https://doi.org/10.1111/j.1471-4159.2005.03019.x Citations: 62
Address correspondence and reprint requests to Elisa Greggio, Department of Biology, University of Padova, Via Ugo Bassi 58b, 35121, Padova, Italy. E‐mail: elisa@cribi.unipd.it
Abstract
Tyrosinase is a key enzyme in the synthesis of melanin in skin and hair and has also been proposed to contribute to the formation of neuromelanin (NM). The presence of NM, which is biochemically similar to melanin in peripheral tissues, identifies groups of neurons susceptible in Parkinson's disease (PD). Whether tyrosinase is beneficial or detrimental to neurons is unclear; whilst the enzyme activity of tyrosinase generates dopamine‐quinones and other oxidizing compounds, NM may form a sink for such radical species. In the present study, we demonstrated that tyrosinase is expressed at low levels in the human brain. We found that mRNA, protein and enzyme activity are all present but at barely detectable levels. In cell culture systems, expression of tyrosinase increases neuronal susceptibility to oxidizing conditions, including dopamine itself. We related these in vitro observations to the human disease by assessing whether there was any genetic association between the gene encoding tyrosinase and idiopathic PD. We found neither genotypic or haplotypic association with three polymorphic markers of the gene. This argues against a strong genetic association between tyrosinase and PD, although the observed contribution to cellular toxicity suggests that a biochemical association is likely.Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease - Greggio - 2005 - Journal of Neurochemistry - Wiley Online Library
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2005.03019.x
Protective and toxic roles of dopamine in Parkinson's disease
Juan Segura‐Aguilar Irmgard Paris Patricia Muñoz Emanuele Ferrari Luigi Zecca Fabio A. Zucca
First published: 18 February 2014 https://doi.org/10.1111/jnc.12686 Citations: 161
Abstract
The molecular mechanisms causing the loss of dopaminergic neurons containing neuromelanin in the substantia nigra and responsible for motor symptoms of Parkinson's disease are still unknown. The discovery of genes associated with Parkinson's disease (such as alpha synuclein (SNCA), E3 ubiquitin protein ligase (parkin), DJ‐1 (PARK7), ubiquitin carboxyl‐terminal hydrolase isozyme L1 (UCHL‐1), serine/threonine‐protein kinase (PINK‐1), leucine‐rich repeat kinase 2 (LRRK2), cation‐transporting ATPase 13A1 (ATP13A), etc.) contributed enormously to basic research towards understanding the role of these proteins in the sporadic form of the disease. However, it is generally accepted by the scientific community that mitochondria dysfunction, alpha synuclein aggregation, dysfunction of protein degradation, oxidative stress and neuroinflammation are involved in neurodegeneration. Dopamine oxidation seems to be a complex pathway in which dopamine o‐quinone, aminochrome and 5,6‐indolequinone are formed. However, both dopamine o‐quinone and 5,6‐indolequinone are so unstable that is difficult to study and separate their roles in the degenerative process occurring in Parkinson's disease. Dopamine oxidation to dopamine o‐quinone, aminochrome and 5,6‐indolequinone seems to play an important role in the neurodegenerative processes of Parkinson's disease as aminochrome induces: (i) mitochondria dysfunction, (ii) formation and stabilization of neurotoxic protofibrils of alpha synuclein, (iii) protein degradation dysfunction of both proteasomal and lysosomal systems and (iv) oxidative stress. The neurotoxic effects of aminochrome in dopaminergic neurons can be inhibited by: (i) preventing dopamine oxidation of the transporter that takes up dopamine into monoaminergic vesicles with low pH and dopamine oxidative deamination catalyzed by monoamino oxidase (ii) dopamine o‐quinone, aminochrome and 5,6‐indolequinone polymerization to neuromelanin and (iii) two‐electron reduction of aminochrome catalyzed by DT‐diaphorase. Furthermore, dopamine conversion to NM seems to have a dual role, protective and toxic, depending mostly on the cellular context.Protective and toxic roles of dopamine in Parkinson's disease - Segura‐Aguilar - 2014 - Journal of Neurochemistry - Wiley Online Library
https://onlinelibrary.wiley.com/doi/10.1111/jnc.12686
What is Dopamine?
https://neurohacker.com/what-is-dopamine
Jun 13, 2018 · The synthesis of L-DOPA by tyrosine hydroxylase (TH) is considered the rate-limiting step (i.e., the slowest step in the pathway, so akin to a bottleneck, which is the most likely place for a metabolic traffic jam to occur) in the synthesis of dopamine.
Effect of the Co-Administration of Vitamin C and Vitamin E on Tyrosine Hydroxylase and Nurr1 Expression in the Prenatal Rat Ventral Mesencephalon
Hae Young LEE, Nibedita NAHA, Najeeb ULLAH, Guang Zhen JIN, Il Keun KONG, Phil Ok KOH, Hwan Hoo SEONG, Myeong Ok KIM
Tyrosine hydroxylase (TH) is the rate-limiting enzyme of dopamine (DA) biosynthesis, which is up-regulated by vitamin C administration. Nurr1 gene is highly expressed in brain and important for midbrain DAergic cell development and survival. But, the role of vitamin C and/or vitamin E during Nurr1 expression is yet to be known. Further, the synergistic effect of vitamins C and E on TH expression has not yet been explored clinically. Therefore, we studied the effects of single or co- administration of vitamin C (0.5 mM) and vitamin E (1 mM) for 72 hr, on both TH and Nurr1 expression in in vitro primary cultured gestational days (GD) 13.5 rat ventral mesencephalon (VM) by Western blot and immunocytochemistry. Our study revealed highest expressions of both TH and Nurr1 in the vitamin C + vitamin E treated group. TH expression was also increased in the vitamin C treated group than that of the control group, but the vitamin E treated group did not show any statistically significant effect. However, both the vitamin C and the vitamin E treated groups revealed increased expression of Nurr1 protein as compared with the control group. The present experimental data suggest that vitamin C can up-regulate the protein expression of TH, but Nurr1 level was elevated either by vitamin C or by vitamin E administration. Further, vitamin E acts synergistically with vitamin C to elevate TH and Nurr1 expression, which is the most novel finding of our study and for the first time; we reported this result, since there have been no published data on the synergistic effect of both the antioxidant vitamins on TH and Nurr1 expression in VM. As the motor function defect due to the progressive loss of DAergic neuron is the major reason of Parkinsonism, therefore, the results of our study finally suggest the effective role of vitamin C and vitamin E during early treatment of Parkinsonism.Effect of the Co-Administration of Vitamin C and Vitamin E on Tyrosine Hydroxylase and Nurr1 Expression in the Prenatal Rat Ventral Mesencephalon
https://www.jstage.jst.go.jp/article/jvms/70/8/70_8_791/_article/-char/ja/
Archives of Biochemistry and Biophysics
Volume 152, Issue 2, October 1972, Pages 515-520
Archives of Biochemistry and Biophysics
Effect of ascorbic acid on tyrosine hydroxylase activity in vivo
National Institute of Nutrition, 1 Toyamacho, Shinjuku-ku, Tokyo 162, Japan
https://doi.org/10.1016/0003-9861(72)90246-9Get rights and content
Abstract
The activity of tyrosine hydroxylase in the homogenate of adrenal gland decreased in scurvy, and it was recovered by the administration of ascorbic acid. The mechanism of increase in tyrosine hydroxylase activity by administration of ascorbic acid has been studied.
The enzyme activities of the adrenal homogenates in nonscorbutic and scorbutic guinea pigs were changed neither by dialysis nor by gel filtration on Sephadex G-25. However, stimulation of enzyme activity by the administration of ascorbic acid, was blocked either by puromycin or by actinomycin D.
Tyrosine hydroxylase was purified by ammonium sulfate fractionation, Sephadex G-200, and hydroxylapatite chromatography. Antibody to the partially purified enzyme was prepared in rabbit. Immunochemical analysis indicated that there was a constant amount of immunochemically precipitable enzyme per unit of enzyme activity. The studies reported here showed that the increase of enzyme activity by the administration of ascorbic acid was due to the increased amount of the enzyme protein.Effect of ascorbic acid on tyrosine hydroxylase activity in vivo - ScienceDirect
https://www.sciencedirect.com/science/article/abs/pii/0003986172902469
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