Low Concentrations Of Dopamine Research Articles

Platinum nanowires/MXene nanosheets/porous carbon ternary nanocomposites for in situ monitoring of dopamine released from neuronal cells

Dopamine is an important neurotransmitter in the body and closely related to many neurodegenerative diseases. Therefore, the detection of dopamine is of great significance for the diagnosis and treatment of diseases, screening of drugs and unraveling of relevant pathogenic mechanisms. However, the low concentration of dopamine in the body and the complexity of the matrix make the accurate detection of dopamine challenging. Herein, an electrochemical sensor is constructed based on ternary nanocomposites consisting of one-dimensional Pt nanowires, two-dimensional MXene nanosheets, and three-dimensional porous carbon. The Pt nanowires exhibit excellent catalytic activity due to the abundant grain boundaries and highly undercoordinated atoms; MXene nanosheets not only facilitate the growth of Pt nanowires, but also enhance the electrical conductivity and hydrophilicity; and the porous carbon helps induce significant adsorption of dopamine on the electrode surface. In electrochemical tests, the ternary nanocomposite-based sensor achieves an ultra-sensitive detection of dopamine (S/N = 3) with a low limit of detection (LOD) of 28 nM, satisfactory selectivity and excellent stability. Furthermore, the sensor can be used for the detection of dopamine in serum and in situ monitoring of dopamine release from PC12 cells. Such a highly sensitive nanocomposite sensor can be exploited for in situ monitoring of important neurotransmitters at the cellular level, which is of great significance for related drug screening and mechanistic studies.

Dopamine and its precursor levodopa inactivate SARS-CoV-2 main protease by forming a quinoprotein

Many studies show either the absence, or very low levels of, SARS-CoV-2 viral RNA and/or antigen in the brain of COVID-19 patients. Reports consistently indicate an abortive infection phenomenon in nervous cells despite the fact that they contain the SARS-CoV-2 receptor, ACE2. Dopamine levels in different brain regions are in the range of micromolar to millimolar concentrations. We have shown that sub-micromolar to low micromolar concentrations of dopamine or its precursor (levodopa) time- and dose-dependently inhibit the activity of SARS-CoV-2 main protease (Mpro), which is vital for the viral life cycle, by forming a quinoprotein. Thiol detection coupled with the assessment of Mpro activity suggests that among the 12 cysteinyl thiols, the active site, Cys145-SH, is preferentially conjugated to the quinone derived from the oxidation of dopamine or levodopa. LC-MS/MS analyses show that the Cys145-SH is covalently conjugated by dopamine- or levodopa-o-quinone. These findings help explain why SARS-CoV-2 causes inefficient replication in many nerve cell lines. It is well recognized that inhaled pulmonary drug delivery is the most robust therapy pathway for lung diseases. CVT-301 (orally inhaled levodopa) was approved by the FDA as a drug for Parkinson's patients prior to the outbreak of COVID-19 in 2018. Based on the fact that SARS-CoV-2 causes inefficient replication in the CNS with abundant endogenous Mpro inhibitor in addition to the current finding that levodopa has an Mpro-inhibitory effect somewhat stronger than dopamine, we should urgently investigate the use of CVT-301 as a lung-targeting, COVID-19, Mpro inhibitor.

Polydopamine-coated photoautotrophic bacteria for improving extracellular electron transfer in living photovoltaics

Living photovoltaics are microbial electrochemical devices that use whole cell–electrode interactions to convert solar energy to electricity. The bottleneck in these technologies is the limited electron transfer between the microbe and the electrode surface. This study focuses on enhancing this transfer by engineering a polydopamine (PDA) coating on the outer membrane of the photosynthetic microbe Synechocystis sp. PCC6803. This coating provides a conductive nanoparticle shell to increase electrode adhesion and improve microbial charge extraction. A combination of scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV–Vis absorption, and Raman spectroscopy measurements were used to characterize the nanoparticle shell under various synthesis conditions. The cell viability and activity were further assessed through oxygen evolution, growth curve, and confocal fluorescence microscopy measurements. The results show sustained cell growth and detectable PDA surface coverage under slightly alkaline conditions (pH 7.5) and at low initial dopamine (DA) concentrations (1 mM). The exoelectrogenicity of the cells prepared under these conditions was also characterized through cyclic voltammetry (CV) and chronoamperometry (CA). The measurements show a three-fold enhancement in the photocurrent at an applied bias of 0.3 V (vs. Ag/AgCl [3 M KCl]) compared to non-coated cells. This study thus lays the framework for engineering the next generation of living photovoltaics with improved performances using biosynthetic electrodes.

Alkaline liquid-derived NaxTi11.5MoVOx/C-40 material with controlled electron transfer rate for sensitive electrochemical detection of dopamine

The neurotransmitter dopamine (DA) is associated with many physiological and pathological processes, so the importance of low detection limits and high sensitivity analysis cannot be overstated, especially for early disease detection. Here, 2 M NaOH aqueous solution is used to precipitate metal ions in an ethanol solution containing carbon black (CB), and then nanocomposite catalysts (NaxTi11.5MoVOx/C-40 (40 denoted as 40 mg CB)) were obtained by calcining the precipitation. When used for DA detection, NaxVOx acts as the main active site for electrochemical oxidation of DA and NaxTi11.5MoOx plays a role in facilitating the binding of DA to the active site and stabilizing the active site. The NaxTi11.5MoVOx/C-40 electrochemical biosensor has a limit of detection (LOD) of 0.003 μM with a linear range of 0.005–51.665 μM for DA. This sensor can be used to sensitively identify the concentration of DA in human blood and urine. Catalysts containing varying amounts of CB exhibit diverse electron transfer rates, and surprisingly, we found that the appropriate electron transfer rate is optimal for the detection of low concentrations of DA. Because the performance of the electrochemical biosensors is affected by both the activity of the catalysts and the accuracy of the electrochemical testing instrumentation. To better explain this phenomenon, we propose the concept of resolution (Rn) and present the formula to derive it, offering a new approach to evaluating the performance of electrochemical biosensors.

Impaired night-time mobility in patients with Parkinson’s disease: a systematic review

Impaired bed mobility (IBM) is a symptom characteristic of patients having difficulty intentionally moving their bodies during nighttime sleep. IBM is one of the most common nocturnal symptoms of Parkinson’s disease (PD) and may lead to extreme pain and even death; it also increases the burden on the patients’ caregivers. In this systematic review, we included 19 studies involving a total of 1,407 patients with PD to observe the causes, assessment methods, and treatment options for IBM. We conclude that the extent of IBM is positively correlated with the severity of symptoms such as disease duration, dyskinesia and decreased sleep quality in patients with PD, and the evidence implies that IBM may be able to serve as a prodromal feature in the development of PD. IBM probably results from low nocturnal dopamine concentrations, reduced function of the spinal tract, torque problems in the muscles, and aging. Therefore, treatment is mostly based on continuously increasing the patient’s nocturnal dopamine concentration, while deep brain stimulation (DBS) also has a mitigating effect on IBM. Both scales and sensors are commonly used to measure the severity of IBM, the wearable device monitoring and scales being updated makes measurements easier and more accurate. The future of the advancement in this field lies in the use of more family-oriented devices (such as smart phones or watches and bracelets, etc.) to monitor IBM’s symptoms and select the appropriate therapeutic treatment according to the severity of the symptoms to relieve patients’ suffering.

Dopamine regulates colonic glial cell-derived neurotrophic factor secretion through cholinergic dependent and independent pathways.

Glial cell-derived neurotrophic factor (GDNF) maintains gut homeostasis. Dopamine promotes GDNF release in astrocytes. We investigated the regulation by dopamine of colonic GDNF secretion. D1 receptor knockout (D1 R-/- ) mice, adeno-associated viral 9-short hairpin RNA carrying D2 receptor (AAV9-shD2 R)-treated mice, 6-hydroxydopamine treated (6-OHDA) rats and primary enteric glial cells (EGCs) culture were used. Incubation fluid from colonic submucosal plexus and longitudinal muscle myenteric plexus were collected for GDNF and ACh measurements. D2 receptor-immunoreactivity (IR), but not D1 receptor-IR, was observed on EGCs. Both D1 receptor-IR and D2 receptor-IR were co-localized on cholinergic neurons. Low concentrations of dopamine induced colonic GDNF secretion in a concentration-dependent manner, which was mimicked by the D1 receptor agonist SKF38393, inhibited by TTX and atropine and eliminated in D1 R-/- mice. SKF38393-induced colonic ACh release was absent in D1 R-/- mice. High concentrations of dopamine suppressed colonic GDNF secretion, which was mimicked by the D2 receptor agonist quinpirole, and absent in AAV-shD2 R-treated mice. Quinpirole decreased GDNF secretion by reducing intracellular Ca2+ levels in primary cultured EGCs. Carbachol ( ACh analogue) promoted the release of GDNF. Quinpirole inhibited colonic ACh release, which was eliminated in the AAV9-shD2 R-treated mice. 6-OHDA treated rats with low ACh and high dopamine content showed decreased GDNF content and increased mucosal permeability in the colon. Low concentrations of dopamine promote colonic GDNF secretion via D1 receptors on cholinergic neurons, whereas high concentrations of dopamine inhibit GDNF secretion via D2 receptors on EGCs and/or cholinergic neurons.

Drug repurposing of dopaminergic drugs to inhibit ataxin-3 aggregation

The accumulation of mutant ataxin-3 (Atx3) in neuronal nuclear inclusions is a pathological hallmark of Machado-Joseph disease (MJD), also known as Spinocerebellar Ataxia Type 3. Decreasing the protein aggregation burden is a possible disease-modifying strategy to tackle MJD and other neurodegenerative disorders for which only symptomatic treatments are currently available. We performed a drug repurposing screening to identify inhibitors of Atx3 aggregation with known toxicological and pharmacokinetic profiles. Interestingly, dopamine hydrochloride and other catecholamines are among the most potent inhibitors of Atx3 aggregation in vitro. Our results indicate that low micromolar concentrations of dopamine markedly delay the formation of mature amyloid fibrils of mutant Atx3 through the inhibition of the earlier oligomerization steps. Although dopamine itself does not cross the blood-brain barrier, dopamine levels in the brain can be increased by low doses of dopamine precursors and dopamine agonists commonly used to treat Parkinsonian symptoms. In agreement, treatment with levodopa ameliorated motor symptoms in a C. elegans model of MJD. These findings suggest a possible application of dopaminergic drugs to halt or reduce Atx3 accumulation in the brains of MJD patients.

Laser-induced graphene electrodes on polyimide membranes modified with gold nanoparticles for the simultaneous detection of dopamine and uric acid in human serum.

The level control of biological active molecules in human body fluids is important for the surveillance of several human diseases. Dopamine (DA) and uric acid (UA) are two important biomarkers of neurological and bone diseases, respectively. Design of sensitive and cost-effective sensors for their detection is an effervescent research field. We report on the straightforward design of laser-induced graphene electrodes (LIGEs) from the laser ablation of a polyimide substrate and their modification by electrochemical deposition of gold nanoparticles (AuNPs/LIGE) and their uses as chemosensors. Electrochemical investigations showed that the presence of gold nanoclusters onto the electrode surface improved the electrochemical surface area (ECSA) and the heterogenous electron transfer (HET) rate. Furthermore, the AuNPs/LIGEs can be used to detect simultaneously low concentrations of DA and UA in presence of ascorbic acid (AA)as an potentiallyinterfering substance at redox potentials of 300 mV, 230 mV and 450 mV and 91 mV, respectively, compared with the Ag/AgCl (3 M KCl) reference electrode in cyclic voltametric. The method displayed linear ranges varying from 2 to 20 μM and 5 to 50 μM, led to limits of detection of 0.37 μM and 0.71 μM for DA and UA, respectively. The AuNPs/LIGE was applied to simultaneously detect both analytes in scarcely diluted human serum with good recoveries. The data show that the recovery percentages ranged from 94% ± 2.1 to 102 % ± 0.5 and from 94% ±0.3 to 112% ± 1.4 for dopamine and uric acid, respectively. Thus, the AuNPs/LIGEs are promising candidates for the detection of other biologically active molecules such as drugs, pesticides, and metabolites.

Lab in tube: comparing different morphological dependent gold nanomaterials towards naked eye and optical sensing of dopamine using aptamer

ABSTRACT Dopamine is a major catecholamine neuro-transmitter that plays important function in the human central nervous system’s function. Dopamine release disorders are linked to neurological illnesses and depression. To comprehend dopamine’s physiological roles, it is vital to monitor dopamine levels at early stage or in regular basis. Many diagnostic procedures are accessible, but they have limitations, thus low-cost and simple ways to test dopamine were needed like colorimetric biosensors. Such biosensors were built with nanoparticles (gold) as a label to help identify targets and the results may be viewed with the naked eye. These gold nanomaterials are available in a range of morphologies, including nanoparticles, nanorods, and others. The present method reported the use of gold nanoparticles (GNPs) and gold nanorods (GNRs) for effective aptamer-based sensing of dopamine. Herein a comparison study was conducted between GNPs and GNRs based apta-sensing of dopamine. Both AuNPs (gold nanoparticles) and AuNRs (gold nanorods) were characterised by SEM (Scanning electron microscope), XRD (X-Ray diffraction) and UV-Vis spectrophotometer (Ultraviolet-Visible spectroscopy). The result claimed that GNRs are more sensitive as they were detecting low concentration of dopamine which was confirmed via UV analysis. Various other parameters such as change in salt concentration, incubation time and interferents were also studied which proved that utilising aptamer and gold-nanorods can be a promising material in the neurotransmitter based diagnosis.

PH Effects Can Dominate Chemical Shift Perturbations in 1H,15N-HSQC NMR Spectroscopy for Studies of Small Molecule/α-Synuclein Interactions.

1H,15N-Heteronuclear Single Quantum Coherence (HSQC) NMR is a powerful technique that has been employed to characterize small-molecule interactions with intrinsically disordered monomeric α-Synuclein (aSyn). We report how solution pH can impact the interpretation of aSyn HSQC NMR spectra and demonstrate that small-molecule formulations (e.g., complexation with acidic salts) can lower sample pH and confound interpretation of drug binding and concomitant protein structural changes. Through stringent pH control, we confirm that several previously identified compounds (EGCG, Baicalin, and Dopamine (DOPA)) as well as a series of potent small-molecule inhibitors of aSyn pathology (Demeclocycline, Ro90-7501, and (±)-Bay K 8644) are capable of direct target engagement of aSyn. Previously, DOPA-aSyn interactions have been shown to elicit a dramatic chemical shift perturbation (CSP) localized to aSyn's H50 at low DOPA concentrations then expanding to aSyn's acidic C-terminal residues at increasing DOPA levels. Interestingly, this CSP profile mirrors our pH titration, where a small reduction in pH affects H50 CSP, and large pH changes induce robust C-terminal CSP. In contrast, under tightly controlled pH 5.0, DOPA induces significant CSPs observed at both ionizable and nonionizable residues. These results suggest that previous interpretations of DOPA-aSyn interactions were conflated with pH-induced CSP, highlighting the need for stringent pH control to minimize potential false-positive interpretations of ligand interactions in HSQC NMR experiments. Furthermore, DOPA's preferential interaction with aSyn under acidic pH represents a novel understanding of DOPA-aSyn interactions that may provide insight into the potential gain of toxic function of aSyn misfolding in α-synucleinopathies.

Parkin Knockdown Modulates Dopamine Release in the Central Complex, but Not the Mushroom Body Heel, of Aging Drosophila.

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons leading to reduced locomotion. Mutations of parkin gene in Drosophila produce the same phenotypes as vertebrate models, but the effect of parkin knockdown on dopamine release is not known. Here, we report age-dependent, spatial variation of dopamine release in the brain of parkin-RNAi adult Drosophila. Dopamine was repetitively stimulated by local application of acetylcholine and quantified by fast-scan cyclic voltammetry in the central complex or mushroom body heel. In the central complex, the main area controlling locomotor function, dopamine release is maintained for repeated stimulations in aged control flies, but lower concentrations of dopamine are released in the central complex of aged parkin-RNAi flies. In the mushroom body heel, the dopamine release decrease in older parkin-RNAi flies is similar to controls. There is not significant dopaminergic neuronal loss even in older parkin knockdown flies, which indicates that the changes in stimulated dopamine release are due to alterations of neuronal function. In young parkin-RNAi flies, locomotion is inhibited by 30%, while in older parkin-RNAi flies it is inhibited by 85%. Overall, stimulated dopamine release is modulated by parkin in an age and brain region dependent manner. Correlating the functional state of the dopaminergic system with behavioral phenotypes provides unique insights into the PD mechanism. Drosophila can be used to study dopamine functionality in PD, elucidate how genetics influence dopamine, and test potential therapies to maintain dopamine release.

Ketamine plasmonic sensor using polyaniline-rGO-Fe3O4 nanocomposite thin layer

Ketamine is a narcotic and palliative substance and the measurement of the low concentration of ketamine is a great intense interest matter in biotechnology and medicine. The surface plasmon resonance imaging method can monitor the low concentration of bio-substance such as ketamine and dopamine. The reduced graphene oxide-Fe 3 O 4 nanoparticles and polyaniline-reduced graphene oxide-Fe 3 O 4 nanocomposite layers as the sensing layer were prepared using sonication and electro-deposition methods, respectively. The average particle size of Fe 3 O 4 was 38.53 nm, and the sensing layer thickness was in the range of 19–24.5 nm. The morphology, functional group, and contribution of chemical elements were investigated using field emission electron microscopy; Fourier transforms infrared spectroscopy, and energy-dispersive X-ray spectroscopy, respectively. The surface plasmon resonance imaging pattern confirmed that the minimum concentration for detecting ketamine, the sensitivity of the sensor, and the response time were about 0.1 mg/L, 0.044, and 220 s, respectively. The affinity constant is 11.19 for the detection of ketamine, and the tendency of the sensing layer to bind the ketamine is higher than dopamine and glucose. • Hazardous chemical detection using surface plasmon resonance image sensor. • Detection of ketmine using surafce plasmon resonance image sensor. • Nanocomposite based on reduced graphene oxide and magnetic nanoparticles for biosensor application. • The effect of low concentration of Ketamine, dopamine, and glucose on the intensity pattern of SPR image.

Dopamine-Mediated Major Depressive Disorder in the Neural Circuit of Ventral Tegmental Area-Nucleus Accumbens-Medial Prefrontal Cortex: From Biological Evidence to Computational Models.

Major depressive disorder (MDD) is a serious psychiatric disorder, with an increasing incidence in recent years. The abnormal dopaminergic pathways of the midbrain cortical and limbic system are the key pathological regions of MDD, particularly the ventral tegmental area- nucleus accumbens- medial prefrontal cortex (VTA-NAc-mPFC) neural circuit. MDD usually occurs with the dysfunction of dopaminergic neurons in VTA, which decreases the dopamine concentration and metabolic rate in NAc/mPFC brain regions. However, it has not been fully explained how abnormal dopamine concentration levels affect this neural circuit dynamically through the modulations of ion channels and synaptic activities. We used Hodgkin-Huxley and dynamical receptor binding model to establish this network, which can quantitatively explain neural activity patterns observed in MDD with different dopamine concentrations by changing the kinetics of some ion channels. The simulation replicated some important pathological patterns of MDD at the level of neurons and circuits with low dopamine concentration, such as the decreased action potential frequency in pyramidal neurons of mPFC with significantly reduced burst firing frequency. The calculation results also revealed that NaP and KS channels of mPFC pyramidal neurons played key roles in the functional regulation of this neural circuit. In addition, we analyzed the synaptic currents and local field potentials to explain the mechanism of MDD from the perspective of dysfunction of excitation-inhibition balance, especially the disinhibition effect in the network. The significance of this article is that we built the first computational model to illuminate the effect of dopamine concentrations for the NAc-mPFC-VTA circuit between MDD and normal groups, which can be used to quantitatively explain the results of existing physiological experiments, predict the results for unperformed experiments and screen possible drug targets.

Dopamine regulates astrocytic IL-6 expression and process formation via dopamine receptors and adrenoceptors

Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those pathological conditions, astrocytes become reactive astrocytes characterized by morphological changes and the release of inflammatory cytokines involved in pathogenesis. However, it remains unclear whether dopamine regulates astrocytic morphology and functions. Elucidating these issues will help us to understand the pathogenesis of neurodegenerative diseases caused by abnormal dopamine signaling. In this study, we investigated the effects of dopamine on IL-6 expression and process formation in rat primary cultured astrocytes and acute hippocampal slices. Dopamine increased IL-6 expression in a concentration-dependent manner, and this was accompanied by CREB phosphorylation. The effects of a low dopamine concentration (1 μM) were inhibited by a D1-like receptor antagonist, whereas the effects of a high dopamine concentration (100 μM) were inhibited by a β-antagonist and enhanced by a D2-like receptor antagonist. Furthermore, dopamine (100 μM) promoted process formation, which was inhibited by a β-antagonist and enhanced by both an α-antagonist and a D2-like receptor antagonist. In acute hippocampal slices, both a D1-like receptor agonist and β-agonist changed astrocytic morphology. Together, these results indicate that dopamine promotes IL-6 expression and process formation via D1-like receptors and β-adrenoceptors. Furthermore, bidirectional regulation exists; namely, the effects of D1-like receptors and β-adrenoceptors were negatively regulated by D2-like receptors and α2-adrenoceptors.

Retinal thinning in phenylketonuria and Gaucher disease type 3

PurposeRetinal alterations in inherited metabolic diseases associated with neurodegeneration are poorly studied. The objective was to study retinal thickness, specifically the components of the ganglion cell complex (GCC)—nerve fiber layer (NFL), ganglion cell layer (GCL), and inner plexiform layer (IPL)—using spectral-domain optical coherence tomography (SD-OCT) in two different diseases with potential dopaminergic depletion, phenylketonuria (PKU) and Gaucher disease type 3 (GD3).MethodsRetinal layers in 19 patients with PKU, 15 patients with GD3, and 93 healthy individuals were measured using peripapillary ring scan and macular SD-OCT. Linear mixed models were computed including an adjustment for age, sex, and spherical equivalent. We calculated Spearman’s rank correlations between retinal layer measurements and clinical and/or laboratory parameters.ResultsThinning of total retinal thickness was found in the macular inner ring (p = 0.002), and outer ring (p = 0.012), sparing the fovea (p = 0.12) in PKU, while in GD3, all subfields were thinned (fovea p < 0.001, inner ring p = 0.047, outer ring 0.07). In both conditions, thinning was most evident in the NFL, GCL, and IPL, while OPL (outer plexiform layer) was thickened. Peripapillary retinal nerve fiber layer measurements remained normal. GCL and IPL in PKU correlated with tyrosine serum concentration.ConclusionThinning of the NFL, GCL, and IPL, with thickened OPL, are both found in PKU and in GD3. Low dopamine concentrations in the retina might promote these effects. However, these data do not give evidence that retinal measurements can be used as a biomarker for disease severity in patients with GD3.

Role of Alpha‐Synuclein in Parkinson's Disease

While Parkinson's Disease is a multifactorial disease, influenced by both genetics and the environment, alpha-synuclein was the first genetic factor to be linked to the disease. It has henceforth become a target in therapeutic research. A-synuclein is a 140 amino acid neuronal protein that primarily regulates synaptic activity. It is considered to be intrinsically disordered as it does not have a defined structure in aqueous solutions. However, the protein forms α-helical structures when it binds to negatively charged lipids, such as phospholipids in cell membranes. Α-synuclein is a member of the synculein protein family, a group of three neuronal proteins with a highly conserved alpha-helical lipid binding domain. Synucleins have been associated with a number of neurodegenerative disorders, including Parkinson's Disease (PD) and Alzheimer's Disease (AD), as well as some cancers. A-synuclein is unique in the synuclein family for its non-amyloid component (NAC) region, which has been linked to the formation of Lewy bodies. The wild type form of α-synuclein is coded from the SNCA gene. This form has several functions, but it primarily functions as a presynaptic protein that controls neurotransmitter release by acting as a chaperone in the folding of Soluble NSF Attachment Protein Receptors (SNAREs). SNAREs mediate vesicle fusion with membranes, while α-synuclein increases local Ca2+ release from microdomains to trigger ATP-induced exocytosis. Certain mutations in SNCA cause α-synuclein to polymerize into protofibrils that eventually coalesce into fibrils, a process called α-synuclein aggregation. Aggregation of α-synuclein leads to the creation of Lewy bodies, toxic clumps in the brains of patients with PD. PD is a progressive neurodegenerative disorder that affects movement. Common symptoms include bradykinesia, muscular rigidity, and tremor. Some studies have shown that deleting the NAC region prevented aggregation of α-synuclein. Other α-synuclein therapies have used receptor blocking strategies to inhibit the spread of the protein to other parts of the brain. There are also a variety of therapies that focus on preventing aggregation by decreasing the amount of α-synuclein in the brain. While such therapies have shown positive results in fruit flies, mice, and rats, human trials have not been conducted. Medications to control symptoms are the main treatment for PD; these medications typically work by increasing or acting as a substitute for dopamine, as PD patients have low dopamine concentrations. In severe cases, surgeries like deep brain stimulations have helped to lessen tremors. Patients are encouraged to make lifestyle changes, such as uptaking aerobic exercise or physical therapy, which can improve symptoms. Further research on the relationship between α-synuclein and Parkinson's Disease is required before human trials can begin. Nonetheless, the results of therapeutic studies have been promising.

A Promising Electrochemical Platform for Dopamine and Uric Acid Detection Based on a Polyaniline/Iron Oxide-Tin Oxide/Reduced Graphene Oxide Ternary Composite.

A ternary polyaniline/Fe2O3-SnO2/reduced graphene oxide (PFSG) nanocomposite was prepared using a simple two-step hydrothermal treatment. The composite was applied as a glassy carbon electrode modifier (GCE) to enhance dopamine (DA) and uric acid (UA) detection. The ternary PFSG composite was compared with its binary precursor Fe2O3-SnO2/reduced graphene oxide (FSG). The influence of the modified GCE electrodes on their performance as a sensing platform was determined. GCE/PFSG showed better sensing parameters than GCE/FSG due to the introduction of polyaniline (PANI), increasing the electrocatalytic properties of the electrode towards the detected analytes. GCE/PFSG enabled the detection of low concentrations of DA (0.076 µM) and UA (1.6 µM). The peak potential separation between DA and UA was very good (180 mV). Moreover, the DA oxidation peak was unaffected even if the concentration of UA was ten times higher. The fabricated sensor showed excellent performance in the simultaneous detection with DA and UA limits of detection: LODDA = 0.15 µM and LODUA = 6.4 µM, and outstanding long-term stability towards DA and UA, holding 100% and 90% of their initial signals respectively, after one month of use.

Single-atom doping of MoS2 with manganese enables ultrasensitive detection of dopamine: Experimental and computational approach.

Two-dimensional transition metal dichalcogenides (TMDs) emerged as a promising platform to construct sensitive biosensors. We report an ultrasensitive electrochemical dopamine sensor based on manganese-doped MoS2 synthesized via a scalable two-step approach (with Mn ~2.15 atomic %). Selective dopamine detection is achieved with a detection limit of 50 pM in buffer solution, 5 nM in 10% serum, and 50 nM in artificial sweat. Density functional theory calculations and scanning transmission electron microscopy show that two types of Mn defects are dominant: Mn on top of a Mo atom (MntopMo) and Mn substituting a Mo atom (MnMo). At low dopamine concentrations, physisorption on MnMo dominates. At higher concentrations, dopamine chemisorbs on MntopMo, which is consistent with calculations of the dopamine binding energy (2.91 eV for MntopMo versus 0.65 eV for MnMo). Our results demonstrate that metal-doped layered materials, such as TMDs, constitute an emergent platform to construct ultrasensitive and tunable biosensors.

Nanosheet composed of gold nanoparticle/graphene/epoxy resin based on ultrasonic fabrication for flexible dopamine biosensor using surface-enhanced Raman spectroscopy

Construction of a fast, easy and sensitive neurotransmitters-based sensor could provide a promising way for the diagnosis of neurological diseases, leading to the discovery of more effective treatment methods. The current work is directed to develop for the first time a flexible Surface-Enhanced Raman Spectroscopy (SERS) based neurotransmitters sensor by using the ultrasonic-assisted fabrication of a new set of epoxy resin (EPR) nanocomposites based on graphene nanosheets (GNS) using the casting technique. The perspicuous epoxy resin was reinforced by the variable loading of GNS giving the general formula GNS/EPR1–5. The designed products have been fabricated in situ while the perspicuous epoxy resin was formed. The expected nanocomposites have been fabricated using 3%, 5%, 10%, 15% and 20% GNS loading was applied for such fabrication process. The chemical, physical and morphological properties of the prepared nanocomposites were investigated by using Fourier transforms infrared spectroscopy, X-ray diffraction, Thermogravimetric analysis, Differential Thermal gravimetry, and field emission scanning electron microscopy methods. The GNS/EPR1–5 nanocomposites were decorated with a layer of gold nanoparticles (Au NPs/GNS/EPR) to create surface-enhanced Raman scattering hot points. The wettability of the Au NPs/GNS/EPR was investigated in comparison with the different nanocomposites and the bare epoxy. Au NPs/GNS/EPR was used as a SERS-active surface for detecting different concentrations of dopamine with a limit of detection of 3.3 µM. Our sensor showed the capability to detect low concentrations of dopamine either in a buffer system or in human serum as a real sample.

Obesogenic diet-associated C-reactive protein predicts reduced central dopamine and corticostriatal functional connectivity in female rhesus monkeys

Alterations in dopamine (DA) signaling and reductions in functional connectivity (FC; a measure of temporal correlations of activity between different brain regions) within dopaminergic reward pathways are implicated in the etiology of psychopathology and have been associated with increased concentrations of inflammatory markers, including C-reactive protein. Peripheral and central inflammatory cytokines that have been shown to disrupt DA signaling and corticostriatal FC are associated with C-reactive protein, an acute phase reactant that is used translationally as a marker of systemic inflammation. One factor that can significantly increase systemic inflammation to produce neuroadaptations in reward pathways is a diet that results in fat mass accumulation (e.g. obesogenic diet). The current study in female rhesus monkeys maintained in a standard laboratory chow (n = 18) or on obesogenic diet (n = 16) for 12-months tested the hypothesis that an obesogenic diet would alter central DA and homovanillic acid (HVA) concentrations, and be associated with increased CRP concentrations and decreased FC between corticostriatal regions at 12-months following dietary intervention. We specifically assessed FC between the nucleus accumbens (NAcc) and two sub-regions of the prefrontal cortex (PFC) previously associated with CRP concentrations, the ventromedial PFC (vmPFC) and the orbitofrontal cortex (OFC), which are also involved in emotional and motivational salience assessment, and in goal-directed behavior, impulse control and the salience/value of food, respectively. Results showed that CSF DA concentrations were decreased (p = 0.002), HVA:DA ratios were increased (p = 0.016), and body mass index was increased (p = 0.047) over the 12-months of consuming an obesogenic diet. At 12-months, females maintained in the obesogenic diet exhibited higher CRP concentrations than females consuming chow-only (p = 0.008). Linear regression analyses revealed significant CRP by dietary condition interactions on DA concentrations (β = −5.10; p = 0.017) and HVA:DA ratios (β = 5.14; p = 0.029). Higher CRP concentrations were associated with lower CSF DA concentrations (r = −0.69; p = 0.004) and greater HVA:DA ratios only in females maintained in the obesogenic dietary condition (r = 0.58; p = 0.024). Resting-state magnetic resonance neuroimaging (rs-fMRI) in a subset of females from each diet condition (n = 8) at 12-months showed that higher CRP concentrations were associated decreased FC between the NAcc and subregions of the prefrontal cortex (PFC; p’s < 0.05). Decreased FC between the NAcc and PFC subregions were also associated with lower concentrations of DA and greater HVA:DA ratios (p’s < 0.05). Overall, these data suggest that increased inflammatory signaling driving heightened CRP levels may mediate the adverse consequences of obesogenic diets on DA neurochemistry and corticostriatal connectivity.