Dopamine Deficiency Research Articles

Ag nanozyme strengthened by folic acid: Superior peroxidase-mimicking activity and application for visual monitoring of dopamine.

Dopamine (DA) is an important neurotransmitter; however, any excess or deficiency of DA will cause several diseases in humans. To monitor DA efficiently and conveniently, a Ag nanozyme strengthened by bioactive folic acid (FA@AgNPs) was developed by homogeneous redox assembly. After the microstructure and performance were characterized in detail, it was noted that the proposed FA@AgNPs possessed superior peroxidase-like activity due to the ultra-small Ag nanoparticles and multiple amino, hydroxyl, and aromatic rings in FA. FA@AgNPs accelerated the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with a low Michaelis constant (Km) and high maximal reaction rate (Vmax). Importantly, the characteristic absorbance intensity of FA@AgNPs-TMB-H2O2 at 652 nm (A652) was exclusively deteriorated in the presence of trace DA, accompanied by a visual color change from blue to colorless. Under the optimized conditions (pH 4.0, 300 μL 1.5 mM TMB, 300 μL 1.0 M H2O2 and incubated for 30 min at room temperature), there expressed an excellent linear relationship between lgA0/A652 and cDA from 1.0 ×10-8 to 6.67×10-6 mol/L with a low limit detection of 7.1×10-10 mol/L (S/N=3). When applied for monitoring of DA in real fruit juice and pharmaceutical samples, the recovery was between 96.6% and 104.9%, with RSD less than 2.2%. The enhanced peroxidase-like activity of the FA@AgNP system and its selective recognition mechanism for DA are also proposed.

Neurophysiological assessment of juvenile parkinsonism due to primary monoamine neurotransmitter disorders

No studies have investigated voluntary movement abnormalities and their neurophysiological correlates in patients with parkinsonism due to inherited primary monoamine neurotransmitter (NT) disorders. Nine NT disorders patients and 16 healthy controls (HCs) were enrolled. Objective measurements of repetitive finger tapping were obtained using a motion analysis system. Primary motor cortex (M1) excitability was assessed by recording the input/output (I/O) curve of motor-evoked potentials (MEP) and using a conditioning test paradigm for short-interval intracortical inhibition (SICI) assessment. M1 plasticity-like mechanisms were indexed according to MEPs amplitude changes after the paired associative stimulation protocol. Patient values were considered abnormal if they were greater or lower than two standard deviations from the average HCs value. Patients with aromatic amino acid decarboxylase, tyrosine hydroxylase, and 6-pyruvoyl-tetrahydropterin synthase defects showed markedly reduced velocity (5/5 patients), reduced movement amplitude, and irregular rhythm (4/5 patients). Conversely, only 1 out of 3 patients with autosomal-dominant GTPCH deficiency showed abnormal movement parameters. Interestingly, none of the patients had a progressive reduction in movement amplitude or velocity during the tapping sequence (no sequence effect). Reduced SICI was the most prominent neurophysiological abnormality in patients (5/9 patients). Finally, the I/O curve slope correlated with movement velocity and rhythm in patients. We provided an objective assessment of finger tapping abnormalities in monoamine NT disorders. We also demonstrated M1 excitability changes possibly related to alterations in motor execution. Our results may contribute to a better understanding of the pathophysiology of juvenile parkinsonism due to dopamine deficiency.

A Riemannian Deep Learning Representation to Describe Gait Parkinsonian Locomotor Patterns.

Parkinson is the second most common neurodegenerative disease, mainly related to progressive locomotor alterations caused by dopamine deficiency. The gait kinematic is a principal disease biomarker that associates patterns like the step length, flexed posture, and bradykinesia with disease progression. Nonetheless, these patterns are analyzed from invasive setups that only capture coarse dynamics at advanced disease stages. This work introduces a very compact and robust deep representation that effectively learns a Riemannian manifold to describe locomotor parkinsonian patterns. Contrary to traditional deep strategies, the presented framework fully explores data geometry from input mean covariance matrices representing video sequences. These symmetric positive definite (SPD) matrices lie in a Riemannian manifold. Then such matrices are projected to the SPD net, which learns a bank of SPD matrices from a non-linear training, that may be exploited in a hierarchical composition from a set of layers. In a final layer, a projection in a Euclidean space allows learning the discriminatory patterns of PD w.r.t control population. In a retrospective study with a total of 22 patients (11 Parkinson's and 11 controls), the proposed approach achieves a remarkable classification between Parkinson's and control video sequences, correctly labeling all Parkinson's patients, and outperforming typical 3D convolutional representations. Clinical relevance- The study of gait parkinsonian descrip-tors computed from a Riemannian geometry, built from a deep representation.

A Parkinsonian Digital Biomarker Learned as an Anomaly Deep Generative Representation.

Parkinson's Disease (PD), the second most common neurodegenerative disorder, is associated with voluntary movement disorders caused by progressive dopamine deficiency. Gait motor alterations constitute a main tool to diagnose, characterize and personalize treatments. Nonetheless, such evaluation is biased by expert observations, reporting a false positive diagnosis up to 24%. Learning computational tools are recently emerged as potential alternatives to support diagnosis and to quantify kinematic patterns during locomotion. Nonetheless, such learning schemes required a large amount of balanced and stratified data examples, which may result unrealistic in clinical scenarios. This work introduces a self-supervised generative representation to discover gait-motion related patterns, under the pretext of video reconstruction and an anomaly detection framework. From the learned scheme, it is recovered a hidden embedding gait descriptor that constitutes a digital biomarker, allowing to discover PD differences regarding a control population. The proposed approach was validated with 11 PD patients (H&Y scale between 2.5 and 3.0) and 11 control subjects, and trained with only control population, achieving an AUC of 99.4% in the classification task. Clinical Relevance- A digital biomarker that helps in the diagnosis of PD using videos of a patient's gait to capture important and relevant motion patterns to avoid subjectivity when an expert made a diagnosis.

Review: Subjective Time Perception, Dopamine Signaling, and Parkinsonian Slowness.

The association between idiopathic Parkinson's disease, a paradigmatic dopamine-deficiency syndrome, and problems in the estimation of time has been studied experimentally for decades. I review that literature, which raises a question about whether and if dopamine deficiency relates not only to the motor slowness that is an objective and cardinal parkinsonian sign, but also to a compromised neural substrate for time perception. Why does a clinically (motorically) significant deficiency in dopamine play a role in the subjective perception of time's passage? After a discussion of a classical conception of basal ganglionic control of movement under the influence of dopamine, I describe recent work in healthy mice using optogenetics; the methodology visualizes dopaminergic neuronal firing in very short time intervals, then allows for correlation with motor behaviors in trained tasks. Moment-to-moment neuronal activity is both highly dynamic and variable, as assessed by photometry of genetically defined dopaminergic neurons. I use those animal data as context to review a large experimental experience in humans, spanning decades, that has examined subjective time perception mainly in Parkinson's disease, but also in other movement disorders. Although the human data are mixed in their findings, I argue that loss of dynamic variability in dopaminergic neuronal activity over very short intervals may be a fundamental sensory aspect in the pathophysiology of parkinsonism. An important implication is that therapeutic response in Parkinson's disease needs to be understood in terms of short-term alterations in dynamic neuronal firing, as has already been examined in novel ways—for example, in the study of real-time changes in neuronal network oscillations across very short time intervals. A finer analysis of a treatment's network effects might aid in any effort to augment clinical response to either medications or functional neurosurgical interventions in Parkinson's disease.

Therapeutic Effects of Quetiapine and 5-HT1A Receptor Agonism on Hyperactivity in Dopamine-Deficient Mice

Some diseases that are associated with dopamine deficiency are accompanied by psychiatric symptoms, including Parkinson’s disease. However, the mechanism by which this occurs has not been clarified. Previous studies found that dopamine-deficient (DD) mice exhibited hyperactivity in a novel environment. This hyperactivity is improved by clozapine and donepezil, which are used to treat psychiatric symptoms associated with dopamine deficiency (PSDD). We considered that DD mice could be used to study PSDD. In the present study, we sought to identify the pharmacological mechanism of PSDD. We conducted locomotor activity tests by administering quetiapine and drugs that have specific actions on serotonin (5-hydroxytryptamine [5-HT]) receptors and muscarinic receptors. Changes in neuronal activity that were induced by drug administration in DD mice were evaluated by examining Fos immunoreactivity. Quetiapine suppressed hyperactivity in DD mice while the 5-HT1A receptor antagonist WAY100635 inhibited this effect. The number of Fos-positive neurons in the median raphe nucleus increased in DD mice that exhibited hyperactivity and was decreased by treatment with quetiapine and 5-HT1A receptor agonists. In conclusion, hyperactivity in DD mice was ameliorated by quetiapine, likely through 5-HT1A receptor activation. These findings suggest that 5-HT1A receptors may play a role in PSDD, and 5-HT1A receptor-targeting drugs may help improve PSDD.

Systemic D1-R and D2-R antagonists in non-human primates differentially impact learning and memory while impairing motivation and motor performance.

Dopamine (DA) modulates cognition in part via differential activation of D1 and D2 receptors within the striatum and prefrontal cortex, yet evidence for cognitive impairments stemming from DA blockade or deficiency is inconsistent. Given the predominance of D1 over D2 receptors (R) in the prefrontal cortex of primates, D1-R blockade should more strongly influence frontal executive function (including working memory), while D2-R blockade should impair processes more strongly associated with the dorsal striatum (including cognitive flexibility, and learning). To test how systemic DA blockade disrupts cognition, we administered D1-R and D2-R like antagonists to healthy monkeys while they performed a series of cognitive tasks. Two selective DA receptor antagonist drugs (SCH-23390 hydrochloride: D1/D5-R antagonist; or Eticlopride hydrochloride: D2/D3-R antagonist) or placebo (0.9% saline) were systemically administered. Four tasks were used: (1) 'visually guided reaching', to test response time and accuracy, (2) 'reversal learning', to test association learning and attention, (3) 'self-ordered sequential search' to test spatial working memory, and (4) 'delayed match to sample' to test object working memory. Increased reach response times and decreased motivation to work for liquid reward was observed with both the D1/D5-R and D2/D3-R antagonists at the maximum dosages that still enabled task performance. The D2/D3-R antagonist impaired performance in the reversal learning task, while object and spatial working memory performance was not consistently affected in the tested tasks for either drug. These results are consistent with the theory that systemic D2/D3-R antagonists preferentially influence striatum processes (cognitive flexibility) while systemic D1/D5-R administration is less detrimental to frontal executive function.

Restless Leg Syndrome in Hemodialysis Patients: A Narrative Review.

Restless legs syndrome (RLS) is a clinical entity characterized by sensory-motor manifestations commonly observed in end-stage renal illness. Evidence suggests that RLS is a multifactorial phenomenon that can be influenced by many critical factors, including genetic predisposition, dietary patterns, and deficiency in some vitamins. Iron metabolism disorders and metabolic derangements have been generally accepted as predisposing elements in RLS. Furthermore, both pharmacological and neuroimaging studies demonstrated dopamine deficiency and dopamine receptors decrease in basal ganglia during RLS. A literature search was done in three databases (PubMed, Google Scholar, and Cochrane) to identify the pertinent articles discussing the epidemiology, pathogenesis, and management of RLS in hemodialysis patients. RLS can affect the morbidity and mortality of patients treated with dialysis. It also has significant impacts on the quality of life since it can lead to insomnia, increased fatigue, mental health troubles, and other movement problems. Appropriate measures should be considered in this particular population so to prevent and treat RLS. Many drugs and other nonpharmacological methods have been investigated to attenuate the disease's severity. No treatment, however, could offer long-term effects. Further efforts are still required to improve the understanding of RLS pathogenic trends to find more specific and efficient therapies. A wide range of treatment options is available. However, it can be individualized according to the patients' several factors.

MicroRNAs miR-14 and miR-2766 regulate tyrosine hydroxylase to control larval-pupal metamorphosis in Helicoverpa armigera.

The cotton bollworm, Helicoverpa armigera, is a worldwide polyphagous pest, causing huge economic losses in vegetable, cotton and corn crops, among others. Owing to long-term exposure to Bacillus thuringiensis (Bt) toxins, evolution of resistance has been detected in this pest. As a conservative and effective neurotransmitter, dopamine (DA) has an important role in insect growth and development. In this study, we investigated the regulatory functions of DA and its associated non-coding RNA in metamorphosis in H. armigera. Expression profiles indicated that DA and DA pathway genes were highly expressed during larval-pupal metamorphosis in H. armigera. RNA interference and pharmacological experiments confirmed that tyrosine hydroxylase (TH), dopa decarboxylase, vesicular amine transporter and DA receptor 2 are critical genes related to the development of H. armigera from larvae to pupae. We also found that miR-14 and miR-2766 targeted the 3' untranslated region to post-transcriptionally regulate HaTH function. Application of miR-2766 and miR-14 antagomirs significantly increased levels of HaTH transcripts and proteins, while injection of miR-2766 and miR-14 agomirs not only suppressed messenger RNA and protein levels of HaTH, but also resulted in defective pupation in H. armigera. These results suggest that DA deficiency inhibits larval-pupal metamorphosis in H. armigera. Potentially, DA pathway genes and their microRNAs could be used as a novel target for H. armigera management. © 2022 Society of Chemical Industry.

Apigenin Attenuates Functional and Structural Alterations via Targeting NF-kB/Nrf2 Signaling Pathway in LPS-Induced Parkinsonism in Experimental Rats : Apigenin Attenuates LPS-Induced Parkinsonism in Experimental Rats.

Parkinson's disease (PD) is a progressive hypokinetic movement disorder caused by selective degeneration of dopaminergic neurons in striatum and dopamine deficiency in a region of the midbrain. LPS is an endotoxin, used as animal model to induce microglial activation, neuroinflammation, oxidative stress, and neurotransmitter alteration with PD-like symptoms. Therefore, to prevent neuroinflammation and neurotransmitter changes and to restore normal brain physiology, we tried apigenin (AGN) alone and in combination with piperine (bioenhancer), in LPS experimental model of rats. In this study, rats were treated with single unilateral intranigral injection of LPS at a dose of 5 μg/5 μl on day 0. The oral administration of AGN (25 and 50 mg/kg; p.o.) alone, AGN (25 mg/kg; p.o.) in combination with piperine (2.5 mg/kg; p.o.), and bromocriptine (10mg/kg; p.o.) started from day 7th once in a day. Intranigral injection of LPS significantly altered body weight and behavioral parameters assessed on weekly basis. Furthermore, the biochemical and neuroinflammatory analysis confirmed (on day 22nd) increased level of nitrite, MDA, SOD, TNF-α, IL-1β, IL-6, and caspase-1, and decreased level of CAT, GSH, and complex-I. Furthermore, altered level of neurotransmitters (DA, GABA, and glutamate) and cellular changes were observed from histopathological and immunohistochemistry (NF-kB and Nrf-2) analysis. Treatment with AGN (25 and 50 mg/kg; p.o.) alone and AGN (25 mg/kg; p.o.) in combination with piperine (2.5 mg/kg; p.o.) significantly attenuated the alteration in body weight, motor impairments, oxidative stress, neuroinflammation, and neurotransmitters in rat brain. The neuroprotective effect of AGN against LPS-induced cell death is attributed by modulating NF-kB and Nrf2 signaling pathway in the striatum.

An Overview of Parkinson's Disease: Curcumin as a Possible Alternative Treatment.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain and basal ganglia, followed by dopamine deficiency in the brain. Dopamine plays a crucial role in motor coordination, memory, and cognition; its decrease in PD leads to dyskinesia, cognitive deficits, and depression. In addition, the formation of alpha-synuclein protein aggregates (Lewy bodies) causes further damage to the CNS. Current treatment options include dopamine precursors, inhibitors of dopamine metabolism, upregulation of autophagy, adenosine A2A antagonists, and surgical intervention as a last resort. A challenge arises from a progressive decrease in treatment efficacy as the disease progresses and this necessitates exploration of adjunctive treatments. Epidemiological studies suggest that the prevalence of PD varies between ethnic groups of Caucasians, Asians, and African Americans. Notably, the prevalence of PD is lower in countries of Southeastern Asia including India. The differences in the diet of various ethnic groups may suggest an origin for this difference in the prevalence of PD. One staple ingredient in traditional Asian cuisine is turmeric. Curcuma longa, popularly known as turmeric, is an orange tuberous rhizome that has been used for centuries in traditional Indian cuisine and traditional medicine. Turmeric contains curcumin, a potent antioxidant that scavenges reactive oxygen species and chelates toxic metals. Curcumin has been proposed to be a neuroprotective agent due to its potent antioxidative properties. Though preliminary studies in animal model systems have suggested a protective effect of curcumin on dopaminergic neurons, the direct benefits of curcumin on the progress of PD remains poorly understood. In this review, we explore the promising use of curcumin as an adjunct to conventional PD treatments in order to enhance treatment and improve outcomes.

Effective monitoring and prediction of Parkinson disease in Smart Cities using intelligent health care system

Parkinson Disease (PD) is a severe chronic and progressive neuro-degenerative nerve disease effects the central nervous system associated with the dopamine deficiency widespread in the world. It is a worldwide public health problem of huge measurement. It is a familiar statistic that around one million people suffer from PD in the United States of America and as a whole around 5 million people suffering from PD worldwide. Therefore, it is vital challenge to predict PD in early stages so that initial plan for the needed treatment can be made. However, imbalanced nature of data sets hampered the mining of medical resource data. In this paper, we proposed an approach for detecting and tracking PD intensity using enhanced SMOTE and XGBoost in Fog Computing on UCI’s Parkinson’s Telemonitoring Voice Data Set of individuals. Numerous investigations were executed and the results of the proposed framework achieve 96.43% accuracy on test set and 99.49% accuracy on full set in detecting PD.

P209. Combination of Venlafaxine and Brexpiprazole Induces an Early Enhancement in Dopamine Neurons Activity

The addition of a low dose of dopamine (DA) / serotonin1A (5-HT1A) partial agonists, including brexpiprazole (BREX), to selective 5-HT reuptake inhibitors (SSRI) or selective norepinephrine reuptake inhibitors (SNRI), like venlafaxine (VEN) is often used to successfully treat some treatment-resistant major depressive disorder (MDD) patients. Administration of these partial agonists could counterbalance the attenuating actions of SSRIs/SNRIs on firing activity of catecholamine neurons, resulting in reversal of deficient DA and NE tone that could be of crucial importance in the treatment of MDD. This study investigated whether BREX combined with VEN can induce a change in DA neurons activity that is initially not induced by VEN only.

Neuromelanin in Parkinson's Disease: Tyrosine Hydroxylase and Tyrosinase.

Parkinson’s disease (PD) is an aging-related disease and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigrostriatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. The synthesis of human NM is regarded to be similar to that of melanin in melanocytes; melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then, synthesized to NM. Intracellular NM accumulation above a specific threshold has been reported to be associated with DA neuron death and PD phenotypes. This review reports recent progress in the biosynthesis and pathophysiology of NM in PD.

Prevalence of Sexual Dysfunction in Parkinsonian Men: A Literature Review

ABSTRACT Introduction Parkinson's disease (PD) is one of the most common age-related progressive neurodegeneration disorders with incidence increasing 5-10-fold between the sixth to ninth decade of life. Aside from aging, the male sex is also a significant factor in developing PD. Men are twice as likely to develop PD, have an earlier age of disease onset, and an increased rate of disease progression than that of women. Recently, greater attention has been placed towards the quality of life in PD patients, of which non-motor symptoms play a significant role. Sexual dysfunction is an often-overlooked non-motor symptom, which requires patients to reinvent their sexuality thus forcing their partners to cope with these changes in addition to the consequences of Parkinson's disease. Although sexual dysfunction correlates with a reduced marital and life satisfaction, the dysfunction is neglected due to the sensitivity of the topic, prioritizing motor symptom complaints, and attitudes of patients. Objective The purpose of the study is to conduct a systemic review to evaluate the prevalence of the dominant sexual dysfunction characteristics in parkinsonian men to optimize their quality of life. Methods A systemic review was conducted according to the methodology following the PRISMA guidelines. A search was carried out across PubMed, CINAHL, Academic Search Complete, and PsychInfo using the term “Parkinson's disease” and “Sexual Dysfunction” with the latter expanded to include related terms such as “libido,” “low libido,” “impotence,” “erectile dysfunction,” “ejaculation,” and “orgasmic disorder.” There were no temporal or demographic restriction. Results A total of 956 references were identified, 428 were directed for reading titles and abstracts. A total of 81 articles were excluded for full-text reading. Based on inclusion and exclusion criteria, 15 studies met the criteria and were included into the review. The studies were published between 1990 and 2020. It was not possible to perform a meta-analysis due to the heterogeneity present in the studies. In the selected studies, six scales were used to measure sexual dysfunction: Arizona Sexual Experience Scale (ASEX), Brief Index for Sexual Function (BISF), International Index for Erectile Dysfunction (IIEF), Israeli Sexual Behavior Inventory (ISBI), Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT), and in-house questionnaires. Across the six sexual dysfunction scales, the average reported impaired libido was 40.93% (range = 2%-83%), erectile dysfunction was 54.27% (range = 21.05%-79%), ejaculatory dysfunction was 37.83% (range = 3.16%-79%), and orgasmic dysfunction was 47.88% (range = 0%-87%). Conclusions The review indicates a high prevalence of sexual dysfunction in parkinsonian men; however, insufficient evidence to support or refute the significance of the sexual dysfunction parameters in parkinsonian men. A link between Parkinson's disease and sexual dysfunction via dopamine deficiency and psychosocial deficits has been hypothesized. Increasing awareness and addressing the usually overlooked sexual dysfunction in parkinsonian men can potentially improve their quality of life significantly. Health care providers may consider initiating a conversation regarding sexual function or refer to a sexual medicine specialist thus optimizing the non-motor aspect of parkinsonian men's quality of life. Disclosure No

Pathophysiological significance of increased \u03b1-synuclein deposition in sympathetic nerves in Parkinson\u2019s disease: a post-mortem observational study

BackgroundParkinson’s disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart. Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker; however, whether α-syn buildup is pathophysiological has been unclear. If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples.MethodsWe assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innervation) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control subjects who did not have a neurodegenerative disease.ResultsThe PD group had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times control, P < 0.0001), SMG (35 times control, P = 0.0011), and myocardium (11 times control, P = 0.0011). Myocardial TH in the PD group was decreased by 65% compared to the control group (P = 0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG. Similarly, myocardial NE was decreased by 92% in the PD group (P < 0.0001), but the groups did not differ in NE in either scalp skin or SMG.ConclusionsPD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG, augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.

The Influence of ADORA2A on Levodopa-Induced Dyskinesia.

Dopamine deficiency causes Parkinson's disease (PD), and on treatment, levodopa is the gold standard. Various drug-metabolizing enzymes and drug receptors are believed to be involved in prompting dyskinesias due to the extended usage of levodopa. Shreds of evidence in genomic studies have presented that ADORA2A receptor antagonism has beneficial outcomes to avoid these drug-induced side effects. The aim of this study was to study the polymorphisms of rs2298383, rs35060421, and rs5751876 in the ADORA2A in patients diagnosed as PD and describe their possible relationships with levodopa-induced dyskinesias (LID). One-hundred and seventy-two patients were recruited and separated as the study and the control group. DNA was achieved from peripheral venous blood, high resolution melting analysis, and reverse-transcriptase PCR was performed. The allele differences among the groups were not statistically significant. Although it was not statistically significant, the rs35060421 allele was observed to repeat more frequently. However, we did not find an association between such polymorphisms of ADORA2A and LID. Although this result showed that a higher sample number might produce different results as possible, current results in the Turkish sample indicated that these alleles of ADORA2A might not be related to LID in patients.

Dopaminergic medication reduces interhemispheric hyper-synchronization in Parkinson's disease

IntroductionWe previously reported on interhemispheric cortical hyper synchronization in PD. The aim of the present study was to address the hypothesis that increased interhemispheric cortical synchronization in PD is related to dopamine deficiency and is correlated with motor function. MethodsWe studied participants with PD and characterized cortical synchronization with reference to brain regions. Electroencephalography (EEG) was recorded from 20 participants with PD while OFF and ON their dopaminergic medications (two separate visits), during quiet standing and straight-line walking. Cortical interactions in the theta, alpha, beta, and gamma brain wave frequency bands were evaluated using interhemispheric phase synchronization (inter-PS). ResultsInter-PS values were found to be significantly higher during the OFF state as compared to the ON state in standing and walking trials for theta, alpha and beta bands.In addition, inter-PS reduction from OFF to ON was associated with mobility improvement evaluated by the Timed Up and Go test, and with daily levodopa equivalent dose across individuals. Higher differences in inter-PS values between OFF and ON states were evident mainly in the occipital-parietal cortex. ConclusionsPersons with PD have increased inter-PS during the OFF state compared to their ON state, and this increase in inter-PS is associated with the clinical improvement between OFF and ON. We speculate that these findings, together with previous evidence of higher inter-PS in PD as compared to healthy older adults, reflect neuronal processes consequential to asymmetric subcortical dopamine deficiency.

Ultrasensitive and Selective Electrochemical Detection of Dopamine Based on CuO/PVA Nanocomposite-Modified GC Electrode

At present, the determination of dopamine (DA) is enormously necessary for the human body. Since then, it has played a crucial role in the brain that affects mood, sleep, memory, learning, and concentration. Dopamine insufficiency is a threat to human health. Dopamine recognition is important to avoid this problem. Copper oxide (CuO) nanoparticles are one of the potentials which can be used in the detection of dopamine level in the sample. In this work, CuO was synthesized by a simple chemical precipitation technique and modified by polyvinyl alcohol (PVA) as a capping agent. The nanomaterials manufactured are used for the detection of dopamine in 0.1 M PBS medium at room temperature. The CuO/PVA-modified electrode shows better electrocatalytic activity than CuO/GCE (glassy carbon electrode). The constructed dopamine biosensor of copper oxide-PVA nanocomposites also has extraordinary selectivity, stability, sensitivity (183.12 μA mM-1 cm-2), and a minimum level detection limit of 0.017 μM, is inexpensive, and has minimal effort and rapid detection of dopamine.

The Novel Use of a Synthetic Amino Acid Analog in the Management of Menkes' Disease

AbstractMenkes' disease is a rare X-linked neurodegenerative disorder due to an ATPA7 mutation. This mutation results in a defective copper transport into the lumen of the trans-Golgi network (TGN) of all tissues, except the liver. As the liver remains effective in transporting copper into the TGN, parenteral copper administration is successful in normalizing copper and ceruloplasmin levels. In addition, such treatment improves function of cuproenzymes in the nucleus, cytosol, and mitochondria. However, ATPA7 mutation results in a deficient dopamine β-hydroxylase, a cuproenzyme needed to convert dopamine to norepinephrine (NE). Here, we present the novel use of the synthetic amino acid analog, droxidopa, a prodrug to NE in the management of Menkes' disease. In our 6-year-old Menkes' disease patient treated with daily parenteral copper infusion, we studied clinical features and urine catecholamines levels at baseline and after initiating droxidopa therapy. NE deficiency at baseline was associated with inattention, hypothermia, and dysautonomia. After correction of NE deficiency, the child's symptoms improved. Epinephrine levels remained low. In Menkes' disease, NE deficiency persists after normalization of copper and ceruloplasmin levels. Droxidopa therapy is successful in correcting NE levels and improving quality of life. Further studies are needed.