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1.
Cell Host Microbe ; 32(5): 623-624, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38723597

RESUMO

Common nutrients in our diet often affect our health through unexpected mechanisms. In a recent issue of Nature, Scott et al. show gut microbes convert dietary tryptophan into metabolites activating intestinal dopamine receptors, which can block attachment of bacterial pathogens to host cells.


Assuntos
Dopamina , Microbioma Gastrointestinal , Microbioma Gastrointestinal/fisiologia , Dopamina/metabolismo , Humanos , Receptores Dopaminérgicos/metabolismo , Animais , Triptofano/metabolismo , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/metabolismo , Bactérias/metabolismo , Interações Hospedeiro-Patógeno , Aderência Bacteriana
2.
Mikrochim Acta ; 191(6): 332, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748375

RESUMO

Nifedipine (NIF), as one of the dihydropyridine calcium channel blockers, is widely used in the treatment of hypertension. However, misuse or ingestion of NIF can result in serious health issues such as myocardial infarction, arrhythmia, stroke, and even death. It is essential to design a reliable and sensitive detection method to monitor NIF. In this work, an innovative molecularly imprinted polymer dual-emission fluorescent sensor (CDs@PDA-MIPs) strategy was successfully designed for sensitive detection of NIF. The fluorescent intensity of the probe decreased with increasing NIF concentration, showing a satisfactory linear relationship within the range 1.0 × 10-6 M ~ 5.0 × 10-3 M. The LOD of NIF was 9.38 × 10-7 M (S/N = 3) in fluorescence detection. The application of the CDs@PDA-MIPs in actual samples such as urine and Qiangli Dingxuan tablets has been verified, with recovery ranging from 97.8 to 102.8% for NIF. Therefore, the fluorescent probe demonstrates great potential as a sensing system for detecting NIF.


Assuntos
Carbono , Dopamina , Corantes Fluorescentes , Limite de Detecção , Polímeros Molecularmente Impressos , Nifedipino , Pontos Quânticos , Espectrometria de Fluorescência , Pontos Quânticos/química , Nifedipino/química , Nifedipino/análise , Corantes Fluorescentes/química , Polímeros Molecularmente Impressos/química , Dopamina/urina , Dopamina/análise , Carbono/química , Espectrometria de Fluorescência/métodos , Humanos , Polimerização , Impressão Molecular , Comprimidos/análise
3.
Molecules ; 29(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731427

RESUMO

Dopamine (DA) and uric acid (UA) are essential for many physiological processes in the human body. Abnormal levels of DA and UA can lead to multiple diseases, such as Parkinson's disease and gout. In this work, a three-dimensional reduced graphene oxide-MXene (3D rGO-Ti3C2) composite electrode was prepared using a simple one-step hydrothermal reduction process, which could separate the oxidation potentials of DA and UA, enabling the simultaneous detection of DA and UA. The 3D rGO-Ti3C2 electrode exhibited excellent electrocatalytic activity towards both DA and UA. In 0.01 M PBS solution, the linear range of DA was 0.5-500 µM with a sensitivity of 0.74 µA·µM-1·cm-2 and a detection limit of 0.056 µM (S/N = 3), while the linear range of UA was 0.5-60 µM and 80-450 µM, with sensitivity of 2.96 and 0.81 µA·µM-1·cm-2, respectively, and a detection limit of 0.086 µM (S/N = 3). In 10% fetal bovine serum (FBS) solution, the linear range of DA was 0.5-500 µM with a sensitivity of 0.41 µA·µM-1·cm-2 and a detection limit of 0.091 µM (S/N = 3). The linear range of UA was 2-500 µM with a sensitivity of 0.11 µA·µM-1·cm-2 and a detection limit of 0.6 µM (S/N = 3). The modified electrode exhibited advantages such as high sensitivity, a strong anti-interference capability, and good repeatability. Furthermore, the modified electrode was successfully used for DA measurement in vivo. This could present a simple reliable route for neurotransmitter detection in neuroscience.


Assuntos
Dopamina , Técnicas Eletroquímicas , Eletrodos , Grafite , Ácido Úrico , Grafite/química , Ácido Úrico/análise , Ácido Úrico/sangue , Dopamina/análise , Dopamina/sangue , Técnicas Eletroquímicas/métodos , Limite de Detecção , Oxirredução , Humanos , Titânio/química , Animais
4.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731862

RESUMO

There are currently no disease-modifying therapies for Parkinson's disease (PD), a progressive neurodegenerative disorder associated with dopaminergic neuronal loss. There is increasing evidence that endogenous dopamine (DA) can be a pathological factor in neurodegeneration in PD. Tyrosine hydroxylase (TH) is the key rate-limiting enzyme for DA generation. Drugs that inhibit TH, such as alpha-methyltyrosine (α-MT), have recently been shown to protect against neurodegeneration in various PD models. DA receptor agonists can activate post-synaptic DA receptors to alleviate DA-deficiency-induced PD symptoms. However, DA receptor agonists have no therapeutic effects against neurodegeneration. Thus, a combination therapy with DA receptor agonists plus TH inhibitors may be an attractive therapeutic approach. TH inhibitors can protect and promote the survival of remaining dopaminergic neurons in PD patients' brains, whereas DA receptor agonists activate post-synaptic DA receptors to alleviate PD symptoms. Additionally, other PD drugs, such as N-acetylcysteine (NAC) and anticholinergic drugs, may be used as adjunctive medications to improve therapeutic effects. This multi-drug cocktail may represent a novel strategy to protect against progressive dopaminergic neurodegeneration and alleviate PD disease progression.


Assuntos
Agonistas de Dopamina , Doença de Parkinson , Tirosina 3-Mono-Oxigenase , Animais , Humanos , Dopamina/metabolismo , Agonistas de Dopamina/uso terapêutico , Agonistas de Dopamina/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Inibidores Enzimáticos/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , Tirosina 3-Mono-Oxigenase/metabolismo
5.
Sci Rep ; 14(1): 10835, 2024 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-38736022

RESUMO

Research on the relationships between oligoelements (OE) and the development of cancer or its prevention is a field that is gaining increasing relevance. The aim was to evaluate OE and their interactions with oncology treatments (cytarabine or etoposide) to determine the effects of this combination on biogenic amines and oxidative stress biomarkers in the brain regions of young Wistar rats. Dopamine (DA), 5-Hydroxyindoleacetic acid (5-Hiaa), Glutathione (Gsh), Tiobarbituric acid reactive substances (TBARS) and Ca+2, Mg+2 ATPase enzyme activity were measured in brain regions tissues using spectrophometric and fluorometric methods previously validated. The combination of oligoelements and cytarabine increased dopamine in the striatum but decreased it in cerebellum/medulla-oblongata, whereas the combination of oligoelements and etoposide reduced lipid peroxidation. These results suggest that supplementation with oligoelements modifies the effects of cytarabine and etoposide by redox pathways, and may become promising therapeutic targets in patients with cancer.


Assuntos
Encéfalo , Citarabina , Dopamina , Etoposídeo , Estresse Oxidativo , Ratos Wistar , Animais , Etoposídeo/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Citarabina/farmacologia , Dopamina/metabolismo , Ratos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Masculino , Peroxidação de Lipídeos/efeitos dos fármacos , Suplementos Nutricionais , Glutationa/metabolismo
6.
Sensors (Basel) ; 24(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732893

RESUMO

An abnormal level of dopamine (DA), a kind of neurotransmitter, correlates with a series of diseases, including Parkinson's disease, Willis-Ekbom disease, attention deficit hyperactivity disorder, and schizophrenia. Hence, it is imperative to achieve a precise, rapid detection method in clinical medicine. In this study, we synthesized nanocomposite carbon aerogels (CAs) doped with iron and iron carbide, based on algae residue-derived biomass materials, using Fe(NO3)3 as the iron source. The modified glassy carbon electrode (GCE) for DA detection, denoted as CAs-Fe/GCE, was prepared through surface modification with this composite material. X-ray photoelectron spectroscopy and X-ray diffraction characterization confirmed the successful doping of iron into the as-prepared CAs. Additionally, the electrochemical behavior of DA on the modified electrode surface was investigated and the results demonstrate that the addition of the CAs-Fe promoted the electron transfer rate, thereby enhancing their sensing performance. The fabricated electrochemical DA biosensor exhibits an accurate detection of DA in the concentration within the range of 0.01~200 µM, with a detection limit of 0.0033 µM. Furthermore, the proposed biosensor is validated in real samples, showing its high applicability for the detection of DA in beverages.


Assuntos
Técnicas Biossensoriais , Carbono , Dopamina , Técnicas Eletroquímicas , Eletrodos , Ferro , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Dopamina/análise , Dopamina/química , Carbono/química , Ferro/química , Técnicas Eletroquímicas/métodos , Géis/química , Limite de Detecção , Espectroscopia Fotoeletrônica , Nanocompostos/química
7.
Sensors (Basel) ; 24(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38733043

RESUMO

In this paper, a novel aptamer-modified nitrogen-doped graphene microelectrode (Apt-Au-N-RGOF) was fabricated and used to specifically identify and detect dopamine (DA). During the synthetic process, gold nanoparticles were loaded onto the active sites of nitrogen-doped graphene fibers. Then, aptamers were modified on the microelectrode depending on Au-S bonds to prepare Apt-Au-N-RGOF. The prepared microelectrode can specifically identify DA, avoiding interference with other molecules and improving its selectivity. Compared with the N-RGOF microelectrode, the Apt-Au-N-RGOF microelectrode exhibited higher sensitivity, a lower detection limit (0.5 µM), and a wider linear range (1~100 µM) and could be applied in electrochemical analysis fields.


Assuntos
Aptâmeros de Nucleotídeos , Dopamina , Técnicas Eletroquímicas , Ouro , Grafite , Nanopartículas Metálicas , Microeletrodos , Grafite/química , Dopamina/análise , Dopamina/química , Aptâmeros de Nucleotídeos/química , Ouro/química , Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Limite de Detecção , Nitrogênio/química
8.
Rev Int Androl ; 22(1): 8-16, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38735872

RESUMO

Dopamine and prolactin are the key mediators involved in sexual function in both males and females, but the role of dopamine in female sexual dysfunction (FSD) is still unclear. The aim was to investigate the possible role of dopamine and their relationship with sex steroid hormones (estrogen, progesterone and dehydroepiandrosterone; DHEA) and prolactin levels in Egyptian women suffering from sexual dysfunction. This study included 84 women having sexual dysfunction (FSD group) and 84 normal sexual function (control group). All women were subjected to the questionnaire to assess their demographic and gynecological data as well as female sexual function index (FSFI). Blood samples were collected from all women for measuring serum estradiol, progesterone, DHEA, prolactin and dopamine levels. FSD patients had significantly higher serum progesterone and DHEA and prolactin levels; while significantly lower dopamine and estradiol levels versus controls (p < 0.001). In all women, dopamine level appeared as a predictor of FSD at cut-off point ≤8.8 ng/mL with sensitivity (75%), specificity (92%) and accuracy (83%) (p < 0.001). The low levels of dopamine were associated with significantly higher prevalence in patients with low estradiol (p < 0.001) and high progesterone (p < 0.001), DHEA (p < 0.001) and prolactin (p = 0.004). Also, dopamine was significantly positive correlation with arousal score (r = 0.16, p = 0.04), and negative correlation with age (r = -0.31, p < 0.001), pain score (r = -0.19, p = 0.01), DHEA (r = -0.45, p < 0.001) and prolactin (r = -0.28, p < 0.001). Low serum dopamine level is a potential diagnostic biomarker in women's sexual dysfunction and their association with high prolactin and sex steroid hormones dysfunction.


Assuntos
Biomarcadores , Dopamina , Progesterona , Prolactina , Disfunções Sexuais Fisiológicas , Humanos , Feminino , Dopamina/sangue , Biomarcadores/sangue , Adulto , Disfunções Sexuais Fisiológicas/sangue , Disfunções Sexuais Fisiológicas/diagnóstico , Prolactina/sangue , Progesterona/sangue , Estradiol/sangue , Estudos de Casos e Controles , Egito , Sensibilidade e Especificidade , Inquéritos e Questionários , Adulto Jovem , Pessoa de Meia-Idade , Desidroepiandrosterona/sangue , Hormônios Esteroides Gonadais/sangue
9.
Luminescence ; 39(5): e4760, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738510

RESUMO

The present communication reports on the synthesis of a novel methyl-pyridone azo fluorescent tag (MPAFT) were proven through 1H (NMR), FT-IR, UV-vis, and high-resolution mass spectrometry. The quantum chemical parameters of MPAFT were evaluated using density functional theory (DFT) analysis. It was further investigated for its latent fingerprint (LFPs) in various surfaces and anticounterfeiting applications. By exposing Level I-Level III, ridge features to UV light with a wavelength of 365 nm, a bioimaging investigation has also demonstrated the potential of MPAFT's emission behaviour. The cyclic voltammetry (CV) and linear sweep voltammetry (LSV) at MPAFT/MGCE (modified glassy carbon electrode) were used to explore the electrochemical sensitivity and reliable detection of dopamine (DA) in neutral PBS (pH 7) electrolyte solution, and the results show good sensitivity and detection. The lower detection limit for LSV was 0.81 µM under optimum conditions.


Assuntos
Dopamina , Técnicas Eletroquímicas , Corantes Fluorescentes , Pirazóis , Piridonas , Piridonas/química , Dopamina/análise , Dopamina/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Pirazóis/química , Humanos , Estrutura Molecular , Teoria da Densidade Funcional , Imagem Óptica , Processos Fotoquímicos
10.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731799

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Dopamine (DA) neurons in the substantia nigra pars compacta, which have axonal projections to the dorsal striatum (dSTR), degenerate in PD. In contrast, DA neurons in the ventral tegmental area, with axonal projections to the ventral striatum, including the nucleus accumbens (NAcc) shell, are largely spared. This study aims to uncover the relative contributions of glycolysis and oxidative phosphorylation (OxPhos) to DA release in the striatum. We measured evoked DA release in mouse striatal brain slices using fast-scan cyclic voltammetry applied every two minutes. Blocking OxPhos resulted in a greater reduction in evoked DA release in the dSTR when compared to the NAcc shell, while blocking glycolysis caused a more significant decrease in evoked DA release in the NAcc shell than in the dSTR. Furthermore, when glycolysis was bypassed in favor of direct OxPhos, evoked DA release in the NAcc shell decreased by approximately 50% over 40 min, whereas evoked DA release in the dSTR was largely unaffected. These results demonstrate that the dSTR relies primarily on OxPhos for energy production to maintain evoked DA release, whereas the NAcc shell depends more on glycolysis. Consistently, two-photon imaging revealed higher oxidation levels of DA terminals in the dSTR than in the NAcc shell. Together, these findings partly explain the selective vulnerability of DA terminals in the dSTR to degeneration in PD.


Assuntos
Corpo Estriado , Dopamina , Glicólise , Fosforilação Oxidativa , Animais , Dopamina/metabolismo , Camundongos , Corpo Estriado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neurônios Dopaminérgicos/metabolismo , Núcleo Accumbens/metabolismo
11.
Proc Natl Acad Sci U S A ; 121(22): e2316149121, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38768342

RESUMO

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients. We found that changes in intrinsic functional connectivity of the STN were associated with alterations in speech functions in PD. Interestingly, this relationship was characterized by altered functional connectivity of the dorsolateral and ventromedial subdivisions of the STN with the language network. Crucially, medication-induced changes in functional connectivity between the STN's dorsolateral subdivision and key regions in the language network, including the left inferior frontal cortex and the left superior temporal gyrus, correlated with alterations on a standardized neuropsychological test requiring oral responses. This relation was not observed in the written version of the same test. Furthermore, changes in functional connectivity between STN and language regions predicted the medication's downstream effects on speech-related cognitive performance. These findings reveal a previously unidentified brain mechanism through which dopaminergic medication influences speech function in PD. Our study sheds light into the subcortical-cortical circuit mechanisms underlying impaired speech control in PD. The insights gained here could inform treatment strategies aimed at mitigating speech deficits in PD and enhancing the quality of life for affected individuals.


Assuntos
Idioma , Doença de Parkinson , Fala , Núcleo Subtalâmico , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Núcleo Subtalâmico/fisiopatologia , Núcleo Subtalâmico/efeitos dos fármacos , Masculino , Fala/fisiologia , Fala/efeitos dos fármacos , Feminino , Pessoa de Meia-Idade , Idoso , Imageamento por Ressonância Magnética , Dopamina/metabolismo , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiopatologia , Cognição/efeitos dos fármacos , Dopaminérgicos/farmacologia , Dopaminérgicos/uso terapêutico
12.
Psychopharmacology (Berl) ; 241(6): 1111-1124, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38702473

RESUMO

RATIONALE: Evidence on the effect of dopamine D1-like and D2-like receptor antagonists on licking microstructure and the forced swimming response led us to suggest that (i) dopamine on D1-like receptors plays a role in activating reward-directed responses and (ii) the level of response activation is reboosted based on a process of evaluation of response efficacy requiring dopamine on D2-like receptors. A main piece of evidence in support of this hypothesis is the observation that the dopamine D2-like receptor antagonist raclopride induces a within-session decrement of burst number occurring after the contact with the reward. The few published studies with a detailed analysis of the time-course of this measure were conducted in our laboratory. OBJECTIVES: The aim of this review is to recapitulate and discuss the evidence in support of the analysis of the within-session burst number as a behavioural substrate for the study of the mechanisms governing ingestion, behavioural activation and the related evaluation processes, and its relevance in the analysis of drug effects on ingestion. CONCLUSIONS: The evidence gathered so far suggests that the analysis of the within-session time-course of burst number provides an important behavioural substrate for the study of the mechanisms governing ingestion, behavioural activation and the related evaluation processes, and might provide decisive evidence in the analysis of the effects of drugs on ingestion. However, further evidence from independent sources is necessary to validate the use and the proposed interpretation of this measure.


Assuntos
Dopamina , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Dopamina/metabolismo , Animais , Humanos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/efeitos dos fármacos , Fatores de Tempo , Antagonistas de Dopamina/farmacologia , Recompensa , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Comportamento de Ingestão de Líquido/fisiologia , Antagonistas dos Receptores de Dopamina D2/farmacologia , Antagonistas dos Receptores de Dopamina D2/administração & dosagem
13.
Life Sci ; 348: 122695, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710285

RESUMO

AIMS: To evaluate the basal release of 6-nitrodopamine (6-ND) from human isolated seminal vesicles (HISV) and to characterize its action and origin. MAIN METHODS: Left HISV obtained from patients undergoing prostatectomy surgery was suspended in a 3-mL organ bath containing warmed (37 °C) and gassed (95%O2:5%CO2) Krebs-Henseleit's solution (KHS) with ascorbic acid. An aliquot of 2 mL of the supernatant was used to quantify catecholamines by LC-MS/MS. For functional studies, concentration-responses curves to catecholamines were obtained, and pEC50 and Emax values were calculated. Detection of tyrosine hydroxylase and S100 protein were also carried out by both immunohistochemistry and fluorescence in-situ hybridization assays (FISH). KEY FINDINGS: Basal release of 6-ND was higher than the other catecholamines (14.76 ± 14.54, 4.99 ± 6.92, 3.72 ± 4.35 and 5.13 ± 5.76 nM for 6-ND, noradrenaline, adrenaline, and dopamine, respectively). In contrast to the other catecholamines, the basal release of 6-ND was not affected by the sodium current (Nav) channel inhibitor tetrodotoxin (1 µM; 10.4 ± 8.9 and 10.4 ± 7.9 nM, before and after tetrodotoxin, respectively). All the catecholamines produced concentration-dependent HISV contractions (pEC50 4.1 ± 0.2, 4.9 ± 0.3, 5.0 ± 0.3, and 3.9 ± 0.8 for 6-ND, noradrenaline, adrenaline, and dopamine, respectively), but 6-ND was 10-times less potent than noradrenaline and adrenaline. However, preincubation with very low concentration of 6-ND (10-8 M, 30 min) produced significant leftward shifts of the concentration-response curves to noradrenaline. Immunohistochemical and FISH assays identified tyrosine hydroxylase in tissue epithelium of HISV strips. SIGNIFICANCE: Epithelium-derived 6-ND is the major catecholamine released from human isolated seminal vesicles and that modulates smooth muscle contractility by potentiating noradrenaline-induced contractions.


Assuntos
Dopamina , Norepinefrina , Glândulas Seminais , Humanos , Masculino , Norepinefrina/farmacologia , Norepinefrina/metabolismo , Glândulas Seminais/efeitos dos fármacos , Glândulas Seminais/metabolismo , Dopamina/metabolismo , Dopamina/farmacologia , Pessoa de Meia-Idade , Epitélio/metabolismo , Epitélio/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Idoso , Catecolaminas/metabolismo
14.
Elife ; 122024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747563

RESUMO

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse activity in dopamine axons responsive to both reward and aversive stimuli. Some axons exhibited a preference for reward, while others favored aversive stimuli, and there was a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings indicate that a group of mesocortical dopamine axons encodes aversive-related signals, which are modulated by both classical conditioning across days and trial-by-trial discrimination within a day.


Assuntos
Axônios , Condicionamento Clássico , Neurônios Dopaminérgicos , Córtex Pré-Frontal , Animais , Córtex Pré-Frontal/fisiologia , Camundongos , Axônios/fisiologia , Condicionamento Clássico/fisiologia , Neurônios Dopaminérgicos/fisiologia , Masculino , Recompensa , Dopamina/metabolismo , Camundongos Endogâmicos C57BL , Sinais (Psicologia)
15.
Elife ; 132024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748470

RESUMO

Acetylcholine is widely believed to modulate the release of dopamine in the striatum of mammals. Experiments in brain slices clearly show that synchronous activation of striatal cholinergic interneurons is sufficient to drive dopamine release via axo-axonal stimulation of nicotinic acetylcholine receptors. However, evidence for this mechanism in vivo has been less forthcoming. Mohebi, Collins and Berke recently reported that, in awake behaving rats, optogenetic activation of striatal cholinergic interneurons with blue light readily evokes dopamine release measured with the red fluorescent sensor RdLight1 (Mohebi et al., 2023). Here, we show that blue light alone alters the fluorescent properties of RdLight1 in a manner that may be misconstrued as phasic dopamine release, and that this artefactual photoactivation can account for the effects attributed to cholinergic interneurons. Our findings indicate that measurements of dopamine using the red-shifted fluorescent sensor RdLight1 should be interpreted with caution when combined with optogenetics. In light of this and other publications that did not observe large acetylcholine-evoked dopamine transients in vivo, the conditions under which such release occurs in behaving animals remain unknown.


Assuntos
Neurônios Colinérgicos , Dopamina , Interneurônios , Optogenética , Dopamina/metabolismo , Animais , Interneurônios/metabolismo , Interneurônios/fisiologia , Neurônios Colinérgicos/metabolismo , Neurônios Colinérgicos/fisiologia , Ratos , Optogenética/métodos , Motivação , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiologia , Acetilcolina/metabolismo
16.
PLoS Comput Biol ; 20(5): e1012082, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701077

RESUMO

Many self-motivated and goal-directed behaviours display highly flexible, approximately 4 hour ultradian (shorter than a day) oscillations. Despite lacking direct correspondence to physical cycles in the environment, these ultradian rhythms may be involved in optimizing functional interactions with the environment and reflect intrinsic neural dynamics. Current evidence supports a role of mesostriatal dopamine (DA) in the expression and propagation of ultradian rhythmicity, however, the biochemical processes underpinning these oscillations remain to be identified. Here, we use a mathematical model to investigate D2 autoreceptor-dependent DA self-regulation as the source of ultradian behavioural rhythms. DA concentration at the midbrain-striatal synapses is governed through a dual-negative feedback-loop structure, which naturally gives rise to rhythmicity. This model shows the propensity of striatal DA to produce an ultradian oscillation characterized by a flexible period that is highly sensitive to parameter variations. Circadian (approximately 24 hour) regulation consolidates the ultradian oscillations and alters their response to the phase-dependent, rapid-resetting effect of a transient excitatory stimulus. Within a circadian framework, the ultradian rhythm orchestrates behavioural activity and enhances responsiveness to an external stimulus. This suggests a role for the circadian-ultradian timekeeping hierarchy in governing organized behaviour and shaping daily experience through coordinating the motivation to engage in recurring, albeit not highly predictable events, such as social interactions.


Assuntos
Dopamina , Receptores de Dopamina D2 , Ritmo Ultradiano , Dopamina/metabolismo , Dopamina/fisiologia , Receptores de Dopamina D2/metabolismo , Ritmo Ultradiano/fisiologia , Animais , Modelos Neurológicos , Humanos , Ritmo Circadiano/fisiologia , Corpo Estriado/fisiologia , Corpo Estriado/metabolismo , Biologia Computacional
17.
Proc Natl Acad Sci U S A ; 121(20): e2316658121, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38717856

RESUMO

Individual survival and evolutionary selection require biological organisms to maximize reward. Economic choice theories define the necessary and sufficient conditions, and neuronal signals of decision variables provide mechanistic explanations. Reinforcement learning (RL) formalisms use predictions, actions, and policies to maximize reward. Midbrain dopamine neurons code reward prediction errors (RPE) of subjective reward value suitable for RL. Electrical and optogenetic self-stimulation experiments demonstrate that monkeys and rodents repeat behaviors that result in dopamine excitation. Dopamine excitations reflect positive RPEs that increase reward predictions via RL; against increasing predictions, obtaining similar dopamine RPE signals again requires better rewards than before. The positive RPEs drive predictions higher again and thus advance a recursive reward-RPE-prediction iteration toward better and better rewards. Agents also avoid dopamine inhibitions that lower reward prediction via RL, which allows smaller rewards than before to elicit positive dopamine RPE signals and resume the iteration toward better rewards. In this way, dopamine RPE signals serve a causal mechanism that attracts agents via RL to the best rewards. The mechanism improves daily life and benefits evolutionary selection but may also induce restlessness and greed.


Assuntos
Dopamina , Neurônios Dopaminérgicos , Recompensa , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Neurônios Dopaminérgicos/metabolismo , Humanos , Reforço Psicológico
18.
Food Funct ; 15(10): 5579-5595, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38713055

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder and dopaminergic dysfunction in the prefrontal cortex (PFC) may play a role. Our previous research indicated that theobromine (TB), a methylxanthine, enhances cognitive function in rodents via the PFC. This study investigates TB's effects on hyperactivity and cognitive function in stroke-prone spontaneously hypertensive rats (SHR), an ADHD animal model. Male SHRs (6-week old) received a diet containing 0.05% TB for 40 days, while control rats received normal diets. Age-matched male Wistar-Kyoto rats (WKY) served as genetic controls. During the TB administration period, we conducted open-field tests and Y-maze tasks to evaluate hyperactivity and cognitive function, then assessed dopamine concentrations and tyrosine hydroxylase (TH), dopamine receptor D1-5 (DRD1-5), dopamine transporter (DAT), vesicular monoamine transporter-2 (VMAT-2), synaptosome-associated protein-25 (SNAP-25), and brain-derived neurotrophic factor (BDNF) expressions in the PFC. Additionally, the binding affinity of TB for the adenosine receptors (ARs) was evaluated. Compared to WKY, SHR exhibited hyperactivity, inattention and working memory deficits. However, chronic TB administration significantly improved these ADHD-like behaviors in SHR. TB administration also normalized dopamine concentrations and expression levels of TH, DRD2, DRD4, SNAP-25, and BDNF in the PFC of SHR. No changes were observed in DRD1, DRD3, DRD5, DAT, and VMAT-2 expression between SHR and WKY rats, and TB intake had minimal effects. TB was found to have affinity binding to ARs. These results indicate that long-term TB supplementation mitigates hyperactivity, inattention and cognitive deficits in SHR by modulating dopaminergic nervous function and BDNF levels in the PFC, representing a potential adjunctive treatment for ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Dopamina , Memória de Curto Prazo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Teobromina , Animais , Masculino , Ratos , Teobromina/farmacologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Memória de Curto Prazo/efeitos dos fármacos , Dopamina/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Lobo Frontal/metabolismo , Lobo Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Modelos Animais de Doenças , Proteína 25 Associada a Sinaptossoma/metabolismo
19.
Biosens Bioelectron ; 258: 116370, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38744115

RESUMO

Protein phosphorylation is a significant post-translational modification that plays a decisive role in the occurrence and development of diseases. However, the rapid and accurate identification of phosphoproteins remains challenging. Herein, a high-throughput sensor array has been constructed based on a magnetic bimetallic nanozyme (Fe3O4@ZNP@UiO-66) for the identification and discrimination of phosphoproteins. Attributing to the formation of Fe-Zr bimetallic dual active centers, the as-prepared Fe3O4@ZNP@UiO-66 exhibits enhanced peroxidase-mimicking catalytic activity, which promotes the electron transfer from Zr center to Fe(II)/Fe(III). The catalytic activity of Fe3O4@ZNP@UiO-66 can be selectively inhibited by phosphoproteins due to the strong interaction between phosphate groups and Zr centers, as well as the ultra-robust antifouling capability of zwitterionic dopamine nanoparticle (ZNP). Considering the diverse binding affinities between various proteins with the nanozyme, the catalytic activity of Fe3O4@ZNP@UiO-66 can be changed to various degree, leading to the different absorption responses at 420 nm in the hydrogen peroxide (H2O2) - 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system. By simply extracting different absorbance intensities at various time points, a sensor array based on reaction kinetics for the discrimination of phosphoproteins from other proteins is constructed through linear discriminant analysis (LDA). Besides, the quantitative determination of phosphoproteins and identification of protein mixtures have been realized. Further, based on the differential level of phosphoproteins in cells, the differentiation of cancer cells from normal cells can also be implemented by utilizing the proposed sensor array, showing great potential in disease diagnosis.


Assuntos
Técnicas Biossensoriais , Peróxido de Hidrogênio , Neoplasias , Fosfoproteínas , Zircônio , Técnicas Biossensoriais/métodos , Humanos , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Peróxido de Hidrogênio/química , Zircônio/química , Peroxidase/química , Dopamina/química , Limite de Detecção , Materiais Biomiméticos/química , Catálise
20.
Eur J Neurosci ; 59(10): 2535-2548, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38720367

RESUMO

The maturation of forebrain dopamine circuitry occurs over multiple developmental periods, extending from early postnatal life until adulthood, with the precise timing of maturation defined by the target region. We recently demonstrated in the adult mouse brain that axon terminals arising from midbrain dopamine neurons innervate the anterior corpus callosum and that oligodendrocyte lineage cells in this white matter tract express dopamine receptor transcripts. Whether corpus callosal dopamine circuitry undergoes maturational changes between early adolescence and adulthood is unknown but may be relevant to understanding the dramatic micro- and macro-anatomical changes that occur in the corpus callosum of multiple species during early adolescence, including in the degree of myelination. Using quantitative neuroanatomy, we show that dopamine innervation in the forceps minor, but not the rostral genu, of the corpus callosum, is greater during early adolescence (P21) compared to adulthood (>P90) in wild-type mice. We further demonstrate with RNAscope that, as in the adult, Drd1 and Drd2 transcripts are expressed at higher levels in oligodendrocyte precursor cells (OPCs) and decline as these cells differentiate into oligodendrocytes. In addition, the number of OPCs that express Drd1 transcripts during early adolescence is double the number of those expressing the transcript during early adulthood. These data further implicate dopamine in axon myelination and myelin regulation. Moreover, because developmental (activity-independent) myelination peaks during early adolescence, with experience-dependent (activity-dependent) myelination greatest during early adulthood, our data suggest that potential roles of dopamine on callosal myelination shift between early adolescence and adulthood, from a developmental role to an experience-dependent role.


Assuntos
Corpo Caloso , Camundongos Endogâmicos C57BL , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Animais , Camundongos , Corpo Caloso/metabolismo , Corpo Caloso/crescimento & desenvolvimento , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genética , Masculino , Neurônios Dopaminérgicos/metabolismo , Dopamina/metabolismo , Células Precursoras de Oligodendrócitos/metabolismo , Feminino
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