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Akathisia and Restless Legs Syndrome: Solving the Dopaminergic Paradox.
Ferré, S, Guitart, X, Quiroz, C, Rea, W, García-Malo, C, Garcia-Borreguero, D, Allen, RP, Earley, CJ
Sleep medicine clinics. 2021;(2):249-267
Abstract
Akathisia is an urgent need to move that is associated with treatment with dopamine receptor blocking agents (DRBAs) and with restless legs syndrome (RLS). The pathogenetic mechanism of akathisia has not been resolved. This article proposes that it involves an increased presynaptic dopaminergic transmission in the ventral striatum and concomitant strong activation of postsynaptic dopamine D1 receptors, which form complexes (heteromers) with dopamine D3 and adenosine A1 receptors. It also proposes that in DRBA-induced akathisia, increased dopamine release depends on inactivation of autoreceptors, whereas in RLS it depends on a brain iron deficiency-induced down-regulation of striatal presynaptic A1 receptors.
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2.
Electrochemical Biosensing of Dopamine Neurotransmitter: A Review.
Lakard, S, Pavel, IA, Lakard, B
Biosensors. 2021;(6)
Abstract
Neurotransmitters are biochemical molecules that transmit a signal from a neuron across the synapse to a target cell, thus being essential to the function of the central and peripheral nervous system. Dopamine is one of the most important catecholamine neurotransmitters since it is involved in many functions of the human central nervous system, including motor control, reward, or reinforcement. It is of utmost importance to quantify the amount of dopamine since abnormal levels can cause a variety of medical and behavioral problems. For instance, Parkinson's disease is partially caused by the death of dopamine-secreting neurons. To date, various methods have been developed to measure dopamine levels, and electrochemical biosensing seems to be the most viable due to its robustness, selectivity, sensitivity, and the possibility to achieve real-time measurements. Even if the electrochemical detection is not facile due to the presence of electroactive interfering species with similar redox potentials in real biological samples, numerous strategies have been employed to resolve this issue. The objective of this paper is to review the materials (metals and metal oxides, carbon materials, polymers) that are frequently used for the electrochemical biosensing of dopamine and point out their respective advantages and drawbacks. Different types of dopamine biosensors, including (micro)electrodes, biosensing platforms, or field-effect transistors, are also described.
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3.
Graphene and Carbon Nanotube-based Electrochemical Sensing Platforms for Dopamine.
Islam, S, Shaheen Shah, S, Naher, S, Ali Ehsan, M, Aziz, MA, Ahammad, AJS
Chemistry, an Asian journal. 2021;(22):3516-3543
Abstract
Dopamine (DA) is an important neurotransmitter, which is created and released from the central nervous system. It plays a crucial role in human activities, like cognition, emotions, and response to anything. Maladjustment of DA in human blood serum results in different neural diseases, like Parkinson's and Schizophrenia. Consequently, researchers have started working on DA detection in blood serum, which is undoubtedly a hot research area. Electrochemical sensing techniques are more promising to detect DA in real samples. However, utilizing conventional electrodes for selective determination of DA encounters numerous problems due to the coexistence of other materials, such as uric acid and ascorbic acid, which have an oxidation potential close to DA. To overcome such problems, researchers have put their focus on the modification of bare electrodes. The aim of this review is to present recent advances in modifications of most used bare electrodes with carbonaceous materials, especially graphene, its derivatives, and carbon nanotubes, for electrochemical detection of DA. A brief discussion about the mechanistic phenomena at the electrode interface has also been included in this review.
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4.
The "Sick-but-not-Dead" Phenomenon Applied to Catecholamine Deficiency in Neurodegenerative Diseases.
Goldstein, DS
Seminars in neurology. 2020;(5):502-514
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Abstract
The catecholamines dopamine and norepinephrine are key central neurotransmitters that participate in many neurobehavioral processes and disease states. Norepinephrine is also the main neurotransmitter mediating regulation of the circulation by the sympathetic nervous system. Several neurodegenerative disorders feature catecholamine deficiency. The most common is Parkinson's disease (PD), in which putamen dopamine content is drastically reduced. PD also entails severely decreased myocardial norepinephrine content, a feature that characterizes two other Lewy body diseases-pure autonomic failure and dementia with Lewy bodies. It is widely presumed that tissue catecholamine depletion in these conditions results directly from loss of catecholaminergic neurons; however, as highlighted in this review, there are also important functional abnormalities in extant residual catecholaminergic neurons. We refer to this as the "sick-but-not-dead" phenomenon. The malfunctions include diminished dopamine biosynthesis via tyrosine hydroxylase (TH) and L-aromatic-amino-acid decarboxylase (LAAAD), inefficient vesicular sequestration of cytoplasmic catecholamines, and attenuated neuronal reuptake via cell membrane catecholamine transporters. A unifying explanation for catecholaminergic neurodegeneration is autotoxicity exerted by 3,4-dihydroxyphenylacetaldehyde (DOPAL), an obligate intermediate in cytoplasmic dopamine metabolism. In PD, putamen DOPAL is built up with respect to dopamine, associated with a vesicular storage defect and decreased aldehyde dehydrogenase activity. Probably via spontaneous oxidation, DOPAL potently oligomerizes and forms quinone-protein adducts with ("quinonizes") α-synuclein (AS), a major constituent in Lewy bodies, and DOPAL-induced AS oligomers impede vesicular storage. DOPAL also quinonizes numerous intracellular proteins and inhibits enzymatic activities of TH and LAAAD. Treatments targeting DOPAL formation and oxidation therefore might rescue sick-but-not-dead catecholaminergic neurons in Lewy body diseases.
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Putative COVID- 19 Induction of Reward Deficiency Syndrome (RDS) and Associated Behavioral Addictions with Potential Concomitant Dopamine Depletion: Is COVID-19 Social Distancing a Double Edged Sword?
Blum, K, Cadet, JL, Baron, D, Badgaiyan, RD, Brewer, R, Modestino, EJ, Gold, MS
Substance use & misuse. 2020;(14):2438-2442
Abstract
The overwhelming fatalities of the global COVID-19 Pandemic will have daunting epigenetic sequala that can translate into an array of mental health issues, including panic, phobia, health anxiety, sleep disturbances to dissociative like symptoms including suicide. Method: We searched PUBMED for articles listed using the search terms "COVID 19 Pandemic", COVID19 and genes," "stress and COVID 19", Stress and Social distancing: Results: Long-term social distancing may be neurologically harmful, the consequence of epigenetic insults to the gene encoding the primary receptor for SARS-CoV2, and COVID 19. The gene is Angiotensin I Converting-Enzyme 2 (ACE2). According to the multi-experiment matrix (MEM), the gene exhibiting the most statistically significant co-expression link to ACE2 is Dopa Decarboxylase (DDC). DDC is a crucial enzyme that participates in the synthesis of both dopamine and serotonin. SARS-CoV2-induced downregulation of ACE2 expression might reduce dopamine and serotonin synthesis, causing hypodopaminergia. Discussion: Indeed, added to the known reduced dopamine function during periods of stress, including social distancing the consequence being both genetic and epigenetic vulnerability to all Reward Deficiency Syndrome (RDS) addictive behaviors. Stress seen in PTSD can generate downstream alterations in immune functions by reducing methylation levels of immune-related genes. Conclusion: Mitigation of these effects by identifying subjects at risk and promoting dopaminergic homeostasis to help regulate stress-relative hypodopaminergia, attenuate fears, and prevent subsequent unwanted drug and non-drug RDS type addictive behaviors seems prudent.
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The Principle of Nanomaterials Based Surface Plasmon Resonance Biosensors and Its Potential for Dopamine Detection.
Kamal Eddin, FB, Fen, YW
Molecules (Basel, Switzerland). 2020;(12)
Abstract
For a healthy life, the human biological system should work in order. Scheduled lifestyle and lack of nutrients usually lead to fluctuations in the biological entities levels such as neurotransmitters (NTs), proteins, and hormones, which in turns put the human health in risk. Dopamine (DA) is an extremely important catecholamine NT distributed in the central nervous system. Its level in the body controls the function of human metabolism, central nervous, renal, hormonal, and cardiovascular systems. It is closely related to the major domains of human cognition, feeling, and human desires, as well as learning. Several neurological disorders such as schizophrenia and Parkinson's disease are related to the extreme abnormalities in DA levels. Therefore, the development of an accurate, effective, and highly sensitive method for rapid determination of DA concentrations is desired. Up to now, different methods have been reported for DA detection such as electrochemical strategies, high-performance liquid chromatography, colorimetry, and capillary electrophoresis mass spectrometry. However, most of them have some limitations. Surface plasmon resonance (SPR) spectroscopy was widely used in biosensing. However, its use to detect NTs is still growing and has fascinated impressive attention of the scientific community. The focus in this concise review paper will be on the principle of SPR sensors and its operation mechanism, the factors that affect the sensor performance. The efficiency of SPR biosensors to detect several clinically related analytes will be mentioned. DA functions in the human body will be explained. Additionally, this review will cover the incorporation of nanomaterials into SPR biosensors and its potential for DA sensing with mention to its advantages and disadvantages.
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Neurochemical features of idiopathic restless legs syndrome.
Jiménez-Jiménez, FJ, Alonso-Navarro, H, García-Martín, E, Agúndez, JAG
Sleep medicine reviews. 2019;:70-87
Abstract
The most important traditional hypotheses of the pathogenesis of idiopathic restless legs syndrome (iRLS) involve dopaminergic dysfunction and iron deficiency. However, a possible role of other neurotransmitter or neuromodulators, mainly glutamate, gamma-hydroxybutyric acid (GABA), and adenosine have been suggested in recent reports. Moreover, iron deficiency in experimental models (which causes sensorimotor symptoms resembling those of RLS) is able to induce changes in dopaminergic, glutamatergic and adenosinergic neurotransmission, thus suggesting its crucial role in the pathogenesis of this disease. Relationship between iRLS and opiates, oxidative stress and nitric oxide, and with vitamin D deficiency has also been reported, although data regarding these variables should be considered as preliminary. In this review, we focus on studies relating to neurochemical findings in iRLS.
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8.
Mean Diffusivity in the Dopaminergic System and Neural Differences Related to Dopaminergic System.
Takeuchi, H, Kawashima, R
Current neuropharmacology. 2018;(4):460-474
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Abstract
BACKGROUND The mean diffusivity (MD) parameter obtained by diffusion tensor imaging provides a measure of how freely water molecules move in brain tissue. Greater tissue density conferred by closely arrayed cellular structures is assumed to lower MD by inhibiting the free diffusion of water molecules. METHODS In this paper, we review studies showing MD variation among regions of the brain dopaminergic system (MDDS), especially subcortical structures such as the putamen, caudate nucleus, and globus pallidus, in different conditions with known associations to dopaminergic system function or dysfunction. The methodologies and background related to MD and MDDS are also discussed. RESULTS Past studies indicate that MDDS is sensitive to pathological derangement of dopaminergic activity, neural changes caused by cognitive and pharmacological interventions that are known to affect the dopaminergic system, and individual character traits related to dopaminergic function. CONCLUSION These results suggest that MDDS can be one useful tool to tap the neural differences related to the dopaminergic system.
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9.
THE RESTLESS LEGS SYNDROME (REVIEW).
Japaridze, G, Kasradze, S, Maisuradze, L, Popp, R, Wetter, T
Georgian medical news. 2018;(285):74-81
Abstract
The restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a common sleep related neurological disorder with prevalence between 1 and 10%, increasing with age. Women are more frequently affected than men. RLS is characterized by an urge to move the legs accompanied by uncomfortable and unpleasant sensations in the legs, worsening of complaints during periods of rest, improvement by movement and an increase of symptoms in the evening or at night. In addition, affected patients may also suffer from severe sleep disorders and negative effects on daily activities. There is often a history of RLS among first-degree relatives, especially with the primary form. Among other, comorbidities or causal factors are iron deficiency, terminal renal insufficiency, pregnancy, polyneuropathy, or psychotropic drugs. The etiology of primary (idiopathic) RLS has not been clarified yet; however, genetic factors and dysfunctional dopaminergic neurotransmission as well as alterations of central iron metabolism play an important role. In addition to non-pharmacological treatment such as lifestyle modifications or behavioral strategies, levodopa, dopamine agonists, or anticonvulsants are effective. Opioids may be used in otherwise refractory forms. In the case of secondary or comorbid RLS, treatment of the underlying disease is necessary.
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10.
Striatal dopamine in Parkinson disease: A meta-analysis of imaging studies.
Kaasinen, V, Vahlberg, T
Annals of neurology. 2017;(6):873-882
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Abstract
A meta-analysis of 142 positron emission tomography and single photon emission computed tomography studies that have investigated striatal presynaptic dopamine function in Parkinson disease (PD) was performed. Subregional estimates of striatal dopamine metabolism are presented. The aromatic L-amino-acid decarboxylase (AADC) defect appears to be consistently smaller than the dopamine transporter and vesicular monoamine transporter 2 defects, suggesting upregulation of AADC function in PD. The correlation between disease severity and dopamine loss appears linear, but the majority of longitudinal studies point to a negative exponential progression pattern of dopamine loss in PD. Ann Neurol 2017;82:873-882.