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Graphene is a promising biomaterial. However, its dispersion in aqueous medium is challenging. This study aimed to modify graphene nanoparticles with L-dopa to improve the properties of experimental dental adhesives. Adhesives were formulated with 0% (control), 0.25%, 0.5%, and 0.75% of graphene, modified or not. Particle modification and dispersion were microscopically assessed. Degree of conversion was tested by Fourier-transform infrared spectroscopy. Flexural strength and modulus of elasticity were evaluated by a 3-point flexural test. Bond strength was tested by shear. To test water sorption/solubility, samples were weighed during hydration and dehydration. Antibacterial activity was tested by Streptococcus mutans colony-forming units quantification. Cytotoxicity on fibroblasts was evaluated through a dentin barrier test. The modification of graphene improved the particle dispersion. Control presented the highest degree of conversion, flexural strength, and bond strength. In degree of conversion, 0.25% of groups were similar to control. In bond strength, groups of graphene modified by L-dopa were similar to Control. The modulus of elasticity was similar between groups. Cytotoxicity and water sorption/solubility decreased as particles increased. Compared to graphene, less graphene modified by L-dopa was needed to promote antibacterial activity. By modifying graphene with L-dopa, the properties of graphene and, therefore, the adhesives incorporated by it were enhanced.

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A fully reusable electrochemical device is proposed for the first time made from laser cutting and a homemade conductive ink composed of carbon and nail polish. As a sensor substrate, we applied polymethyl methacrylate, which allows the surface to be renewed by simply removing and reapplying a new layer of ink. In addition to the ease of renewing the sensor's conductive surface, the design of the device has allowed for the integration of different forms of analysis. The determination of L-Dopa was performed using DPV, which presented a linear response range between 5.0 and 1000.0 µmol L-1, and a LOD of 0.11 µmol L-1. For dopamine, a flow injection analysis system was employed, and using the amperometric technique measurements were performed with a linear ranging from 2.0 to 100.0 µmol L-1 and a LOD of 0.26 µmol L-1. To demonstrate its applicability, the device was used in the quantification of analytes in pharmaceutical drug and synthetic urine samples.

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Levodopa (L-DOPA) is the classical gold standard treatment for Parkinson's disease. However, its chronic administration can lead to the development of L-DOPA-induced dyskinesias (LIDs). Dysregulation of the nitric oxide-cyclic guanosine monophosphate pathway in striatal networks has been linked to deficits in corticostriatal transmission in LIDs. This study investigated the effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on behavioural and electrophysiological outcomes in sham-operated and 6-hydroxydopamine-lesioned rats chronically treated with vehicle or L-DOPA, respectively. In sham-operated animals, systemic administration of SNP increased the spike probability of putative striatal medium spiny neurons (MSNs) in response to electrical stimulation of the primary motor cortex. In 6-hydroxydopamine-lesioned animals, SNP improved the stepping test performance without exacerbating abnormal involuntary movements. Additionally, SNP significantly increased the responsiveness of putative striatal MSNs in the dyskinetic striatum. These findings highlight the critical role of the NO signalling pathway in facilitating the responsiveness of striatal MSNs in both the intact and dyskinetic striata. The study suggests that SNP has the potential to enhance L-DOPA's effects in the stepping test without exacerbating abnormal involuntary movements, thereby offering new possibilities for optimizing Parkinson's disease therapy. In conclusion, this study highlights the involvement of the NO signalling pathway in the pathophysiology of LIDs.

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The use of transcriptomic data to make inferences about plant metabolomes is a useful tool to help the discovery of important compounds in the available biodiversity. To unveil previously undiscovered metabolites of Coffea, of phytotherapeutic and economic value, we employed 24 RNAseq libraries. These libraries were sequenced from leaves exposed to a diverse range of environmental conditions. Subsequently, the data were meticulously processed to create models of putative metabolic networks, which shed light on the production of potential natural compounds of significant interest. Then, we selected one of the predicted compounds, the L-3,4-dihydroxyphenylalanine (L-DOPA), to be analyzed by LC-MS/MS using three biological replicates of flowers, leaves, and fruits from Coffea arabica and Coffea canephora. We were able to identify metabolic pathways responsible for producing several compounds of economic importance. One of the identified pathways involved in isoquinoline alkaloid biosynthesis was found to be active and producing L-DOPA, which is a common product of POLYPHENOL OXIDASES (PPOs, EC 1.14.18.1 and EC 1.10.3.1). We show that coffee plants are a natural source of L-DOPA, a widely used medicine for treatment of the human neurodegenerative condition called Parkinson's disease. In addition, dozens of other compounds with medicinal significance were predicted as potential natural coffee products. By further refining analytical chemistry techniques, it will be possible to enhance the characterization of coffee metabolites, enabling a deeper understanding of their properties and potential applications in medicine.

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SUMMARY STATEMENT: NG2-glia alters its dynamics in response to L-DOPA-induced dyskinesia. In these animals, striatal NG2-glia density was reduced with cells presenting activated phenotype while doxycycline antidyskinetic therapy promotes a return to NG2-glia cell density and protein to a not activated state.

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BACKGROUND: Melanin is a natural pigment that can be applied in different fields such as medicine, environment, pharmaceutical, and nanotechnology. Studies carried out previously showed that the melanin produced by the mel1 mutant from Aspergillus nidulans exhibits antioxidant, anti-inflammatory, and antimicrobial activities, without any cytotoxic or mutagenic effect. These results taken together suggest the potential application of melanin from A. nidulans in the pharmaceutical industry. In this context, this study aimed to evaluate the effect of factors L-tyrosine, glucose, glutamic acid, L-DOPA, and copper on melanin production by the mel1 mutant and to establish the optimal concentration of these factors to maximize melanin production. RESULTS: The results showed that L-DOPA, glucose, and copper sulfate significantly affected melanin production, where L-DOPA was the only factor that exerted a positive effect on melanin yield. Besides, the tyrosinase activity was higher in the presence of L-DOPA, considered a substrate required for enzyme activation, this would explain the increased production of melanin in this condition. After establishing the optimal concentrations of the analyzed factors, the melanin synthesis was increased by 640% compared to the previous studies. CONCLUSIONS: This study contributed to elucidating the mechanisms involved in melanin synthesis in A. nidulans as well as to determining the optimal composition of the culture medium for greater melanin production that will make it possible to scale the process for a future biotechnological application.

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An electrochemical sensor for simultaneous determination of Benserazide (BEZ) and levodopa (L-dopa) was successfully developed using a glassy carbon electrode (GCE) modified with multi-walled carbon nanotube and nitrogen-doped titanium dioxide nanoparticles (GCE/MWCNT/N-TiO2). Cyclic voltammetry and square wave voltammetry were employed to investigate the electrochemical behavior of different working electrodes and analytes. In comparison with unmodified GCE, the modified electrode exhibited better electrocatalytic activity towards BEZ and L-dopa and was efficient in providing a satisfactory separation for oxidation peaks, with a potential difference of 140 mV clearly allows the simultaneous determination of these compounds. Under the optimized conditions, linear ranges of 2.0-20.0 and 2.0-70.0 µmol L-1 were obtained for BEZ and L-dopa, respectively, with a limit of detection of 1.6 µmol L-1 for BEZ and 2.0 µmol L-1 for L-dopa. The method was applied in simultaneous determination of the analytes in pharmaceutical samples, and the accuracy was attested by comparison with HPLC-DAD as the reference method, with a relative error lower than 4.0%.

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Multi-recording techniques show evidence that neurons coordinate their firing forming ensembles and that brain networks are made by connections between ensembles. While "canonical" microcircuits are composed of interconnected principal neurons and interneurons, it is not clear how they participate in recorded neuronal ensembles: "groups of neurons that show spatiotemporal co-activation". Understanding synapses and their plasticity has become complex, making hard to consider all details to fill the gap between cellular-synaptic and circuit levels. Therefore, two assumptions became necessary: First, whatever the nature of the synapses these may be simplified by "functional connections". Second, whatever the mechanisms to achieve synaptic potentiation or depression, the resultant synaptic weights are relatively stable. Both assumptions have experimental basis cited in this review, and tools to analyze neuronal populations are being developed based on them. Microcircuitry processing followed with multi-recording techniques show temporal sequences of neuronal ensembles resembling computational routines. These sequences can be aligned with the steps of behavioral tasks and behavior can be modified upon their manipulation, supporting the hypothesis that they are memory traces. In vitro, recordings show that these temporal sequences can be contained in isolated tissue of histological scale. Sequences found in control conditions differ from those recorded in pathological tissue obtained from animal disease models and those recorded after the actions of clinically useful drugs to treat disease states, setting the basis for new bioassays to test drugs with potential clinical use. These findings make the neuronal ensembles theoretical framework a dynamic neuroscience paradigm.

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The facilitation of corticostriatal transmission is modulated by the pharmacological inhibition of striatal phosphodiesterase 10A (PDE10A). Since L-DOPA-induced dyskinesia is associated with abnormal corticostriatal transmission, we hypothesized that inhibition of PDE10A would modulate L-DOPA-induced dyskinesia (LID) by regulating corticostriatal activity. 6-OHDA-lesioned rats were chronically treated with L-DOPA for one week. After that, for two additional weeks, animals were treated with the PDE10A inhibitor PDM-042 (1 and 3 mg/kg) one hour before L-DOPA. Behavioral analyses were performed to quantify abnormal involuntary movements (AIMs) and to assess the antiparkinsonian effects of L-DOPA. Single-unit extracellular electrophysiological recordings were performed in vivo to characterize the responsiveness of MSNs to cortical stimulation. The low dose of PDM-042 had an antidyskinetic effect (i.e., attenuated peak-dose dyskinesia) and did not interfere with cortically evoked spike activity. Conversely, the high dose of PDM-042 did not affect peak-dose dyskinesia, prolonged AIMs, and increased cortically evoked spike activity. These data suggest that the facilitation of corticostriatal transmission is likely to contribute to the expression of AIMs. Therefore, cyclic nucleotide manipulation is an essential target in controlling LID.

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Introduction: Although the diurnal fluctuation of motor dysfunction, reversible with small doses of dopamine, is a cornerstone for the phenotype of the autosomal dominant Segawa syndrome, the non-motor symptoms of this neurotransmitter deficiency have still received limited attention. Objective: This study aims to evaluate non-motor symptoms of this dopa-responsive dystonia through an intrafamilial comparative cross-sectional study. Methods: Seventeen individuals with a c.IVS5 + 3insT (c.626 + 3insT) variation in the GTP cyclohydrolase-1 gene (GCH1, HGNC: 4193) and 34 intrafamilial controls were studied using the Beck Depression Inventory-II, the Wiener Matrizen Test 2, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the MINI/MINI PLUS Questionnaires, the World Health Organization Quality of Life - BREF Instrument and a drug use assessment questionnaire. Results: No significant difference was found between the groups in the prevalence of sleep disorders and in cognitive function. Nevertheless, generalized anxiety disorder (p = 0.050) and attention-deficit/hyperactivity disorder in childhood (p = 0.011) were observed only in individuals without the molecular variation. The group with the GCH1 variation presented a worse perception about how safe they feel in their daily lives (p = 0.034), less satisfaction with themselves (p = 0.049) and with their relationships (p = 0.029), and a higher prevalence of past major depressive episodes before use of L-Dopa (p = 0.046). Conclusion: Low dopamine could have been protective against generalized anxiety disorder and attention-deficit/hyperactivity disorder in childhood in Segawa group individuals. The prevalence of depression was higher in individuals with the molecular variant prior to the L-Dopa treatment. Considering it, the penetrance estimates for the variant carriers increased from 58.8% to up to 88% in this large studied family. Additionally, neuropsychiatric tests of all individuals with a molecular diagnosis in an affected family are a valuable instrument for its clinical management.