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1.
J Gen Physiol ; 155(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36383232

RESUMO

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used to screen and characterize drugs and to reveal mechanisms underlying cardiac diseases. However, before hiPSC-CMs can be used as a reliable experimental model, the physiological mechanisms underlying their normal function should be further explored. Accordingly, a major feature of hiPSC-CMs is automaticity, which is regulated by both Ca2+ and membrane clocks. To investigate the mechanisms coupling these clocks, we tested three hypotheses: (1) normal automaticity of spontaneously beating hiPSC-CMs is regulated by local Ca2+ releases (LCRs) and cAMP/PKA-dependent coupling of Ca2+ clock to M clock; (2) the LCR period indicates the level of crosstalk within the coupled-clock system; and (3) perturbing the activity of even one clock can lead to hiPSC-CM-altered automaticity due to diminished crosstalk within the coupled-clock system. By measuring the local and global Ca2+ transients, we found that the LCRs properties are correlated with the spontaneous beat interval. Changes in cAMP-dependent coupling of the Ca2+ and M clocks, caused by a pharmacological intervention that either activates the ß-adrenergic or cholinergic receptor or upregulates/downregulates PKA signaling, affected LCR properties, which in turn altered hiPSC-CMs automaticity. Clocks' uncoupling by attenuating the pacemaker current If or the sarcoplasmic reticulum Ca2+ kinetics, decreased hiPSC-CMs beating rate, and prolonged the LCR period. Finally, LCR characteristics of spontaneously beating (at comparable rates) hiPSC-CMs and rabbit SAN are similar. In conclusion, hiPSC-CM automaticity is controlled by the coupled-clock system whose function is mediated by Ca2+-cAMP-PKA signaling.


Assuntos
Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Animais , Humanos , Coelhos , Nó Sinoatrial/fisiologia , Cálcio , Potenciais de Ação/fisiologia
2.
J Intensive Care Med ; 38(1): 121-131, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35603752

RESUMO

Sepsis, as an important public health concern, is one of the leading causes of death in hospitals around the world, accounting for 25% of all deaths. Nowadays, several factors contribute to the development of sepsis. The role of the gut microbiota and the response state of the aberrant immune system is dominant. The effect of the human microbiome on health is undeniable, and gut microbiota is even considered a body organ. It is now clear that the alteration in the normal balance of the microbiota (dysbiosis) is associated with a change in the status of immune system responses. Owing to the strong association between the gut microbiota and its metabolites particularly short-chain fatty acids with many illnesses, the gut microbiota has a unique position in the research of microbiologists and even clinicians. This review aimed to analyze studies' results on the association between microbiota and sepsis, with a substantial understanding of their relationship. As a result, an extensive and comprehensive search was conducted on this issue in existing databases.


Assuntos
Microbioma Gastrointestinal , Microbiota , Sepse , Humanos , Microbioma Gastrointestinal/fisiologia , Disbiose , Sistema Imunitário
3.
J Intensive Care Med ; 38(1): 95-105, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35722738

RESUMO

OBJECTIVE: Sepsis is one of the main causes of morbidity and mortality worldwide. Microcirculatory impairment, especially damage to the endothelium and glycocalyx, is often not assessed. The objective of this systematic review and meta-analysis was to summarize the available evidence of the risk of unsatisfactory outcomes in patients with sepsis and elevated glycocalyx injury and endothelial activation biomarkers. DESIGN: A systematic search was carried out on PubMed/MEDLINE, Embase, Cochrane and Google Scholar up to December 31, 2021, including studies in adults and children with sepsis which measured glycocalyx injury and endothelial activation biomarkers within 48 hours of hospital admission. The primary outcome was the risk of mortality from all causes and the secondary outcomes were the risk of developing respiratory failure (RF) and multiple organ dysfunction syndrome (MODS) in patients with elevations of these biomarkers. MEASUREMENTS AND MAIN RESULTS: A total of 17 studies (3,529 patients) were included: 11 evaluated syndecan-1 (n=2,397) and 6 endocan (n=1,132). Syndecan-1 was higher in the group of patients who died than in those who survived [255 ng/mL (IQR: 139-305) vs. 83 ng/mL (IQR:40-111); p=0.014]. Patients with elevated syndecan-1 had a greater risk of death (OR 2.32; 95% CI 1.89, 3.10: p<0.001), MODS (OR 3.3; 95% CI 1.51, 7.25: p=0.003;), or RF (OR 7.53; 95% CI 1.86-30.45: p=0.005). Endocan was higher in patients who died [3.1 ng/mL (IQR 2.3, 3.7) vs. 1.62 ng/mL (IQR 1.2, 5.7); OR 9.53; 95% CI 3.34, 27.3; p<0.001], who had MODS (OR 8.33; 95% CI 2.07, 33.58; p=0.003) and who had RF (OR 9.66; 95% CI 2.26, 43.95; p=0.002). CONCLUSION: Patients with sepsis and abnormal glycocalyx injury and endothelial activation biomarkers have a greater risk of developing respiratory failure, multiple organ failure, and death. Microcirculatory impairment should be routinely evaluated in patients with sepsis, using biomarkers to stratify risk groups.


Assuntos
Insuficiência Respiratória , Sepse , Adulto , Criança , Humanos , Glicocálix , Sindecana-1 , Insuficiência de Múltiplos Órgãos/etiologia , Microcirculação/fisiologia , Sepse/complicações , Biomarcadores , Endotélio
4.
Methods Mol Biol ; 2591: 283-295, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36350555

RESUMO

Ubiquitin modification is known to regulate endocytic trafficking of many different types of cargo in eukaryotic cells, but it can be challenging to determine what role, if any, ubiquitin plays in the trafficking of a novel or uncharacterized endocytic cargo. Here, we describe a useful approach that leverages fusion to deubiquitinase (DUB) catalytic domains to explore the role ubiquitin plays in endocytic trafficking. This approach can be applied to the analysis of many different endocytic cargos in different cell types, and it can also be used to study linkage specificity in endocytic trafficking. Several different trafficking assays are described to illustrate the broad utility of this "DUB fusion" approach.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Endocitose/fisiologia , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Ubiquitina/metabolismo , Enzimas Desubiquitinantes/genética , Enzimas Desubiquitinantes/metabolismo
5.
Radiographics ; 43(1): e220088, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36367822

RESUMO

Arterial spin labeling (ASL) is an emerging noninvasive MRI technique for assessing cerebral perfusion. An important advantage of ASL perfusion is the lack of a requirement for an exogenous tracer. ASL uses magnetically labeled water protons from arterial blood as an endogenous diffusible tracer. For this reason, ASL is an attractive perfusion imaging modality for children and for patients with contraindications or adverse reactions to gadolinium, patients with renal failure, and those who need repeated follow-up imaging. Another advantage of ASL is the possibility of quantifying cerebral blood flow, which provides an opportunity for comparative analysis among multiple longitudinal studies, unlike other MR perfusion techniques, which are semiquantitative and yield relative perfusion parameters. Advances in MRI technology and pulse sequence design have translated ASL beyond the research arena to successful clinical implementation. However, ASL is still underused in routine clinical practice. Some disadvantages of ASL include a lower signal-to-noise ratio and a longer acquisition time than those with dynamic susceptibility contrast-enhanced MRI. Additional factors limiting the use of ASL include variations in existing techniques and pulse sequence design, the complexity of implementation and postprocessing, insufficient experience with and/or knowledge of the potential clinical applications, and the absence of interpretation guidelines. The authors review the technical and physiologic basis of ASL perfusion, as well as artifacts, pitfalls, and its current clinical applications. A practical approach for interpreting ASL findings is also suggested.


Assuntos
Circulação Cerebrovascular , Angiografia por Ressonância Magnética , Criança , Humanos , Marcadores de Spin , Angiografia por Ressonância Magnética/métodos , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Artefatos
6.
Cardiol Clin ; 41(1): 71-80, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36368812

RESUMO

The noninvasive assessment of oxygen consumption, carbon dioxide production, and ventilation during a cardiopulmonary exercise test (CPET) provides insight into the cardiovascular, pulmonary, and metabolic system's ability to respond to exercise. Exercise physiology has been shown to be distinct for competitive athletes and highly active persons (CAHAPs), thus creating more nuanced interpretations of CPET parameters. CPET in CAHAP is an important test that can be used for both diagnosis (provoking symptoms during a truly maximal test) and performance.


Assuntos
Cardiologistas , Teste de Esforço , Humanos , Consumo de Oxigênio/fisiologia , Tolerância ao Exercício , Atletas
7.
Methods Mol Biol ; 2582: 103-126, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36370347

RESUMO

Cell communication network factor 2 (CCN2), also known as connective tissue growth factor (CTGF), is protein inducible in response to TGFß/Smad signal or the transcriptional activity of matrix metalloproteinase 3 (MMP3). We discovered that MMP3 in exosomes is transferable to recipient cells and then translocates into cell nuclei to transactivate the CCN2/CTGF gene. Exosomes and liposomes enable molecular transfection to recipient cells in vitro and in vivo. These small vesicles are surrounded by lipid membranes and carry proteins, RNA, DNA, and small chemicals. Here we define the exosome-based transfection as "exofection." In addition, spinfection increases the efficiencies of transfection, exofection, and viral infection, thus being compatible with various molecular transfer protocols. Here, we provide protocols, tips, and practical examples of transfection, spinfection, exofection, fluorescence microscopy, and luciferase assays to analyze the CCNs gene expression mechanisms.


Assuntos
Metaloproteinase 3 da Matriz , Transdução de Sinais , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Transdução de Sinais/fisiologia , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Transfecção , Luciferases/genética , Luciferases/metabolismo , Fator de Crescimento Transformador beta/genética
8.
Methods Mol Biol ; 2582: 191-208, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36370351

RESUMO

Expanding the number of insulin-producing beta cells through reactivation of their replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Using antibody arrays, we identified CCN4/Wisp1 as a circulating factor enriched in preweaning mice, a period in which beta cells exhibit a dramatic increase in number. This finding led us to investigate the involvement of CCN4 in beta cell proliferation. We demonstrated that CCN4 promotes adult beta cell proliferation in vitro in cultured isolated islets, and in vivo in islets transplanted into the anterior chamber of the eye. In this chapter, we present the methodology that was used to study proliferation in both settings.


Assuntos
Diabetes Mellitus , Células Secretoras de Insulina , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Camundongos , Animais , Células Secretoras de Insulina/fisiologia , Proliferação de Células
9.
Methods Mol Biol ; 2582: 237-253, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36370354

RESUMO

Chemotaxis is a directed migration of cells in response to a gradient of extracellular molecules called chemoattractants. Development, growth, remodeling, and fracture healing of bones are advanced through intramembranous osteogenesis. Chemotaxis of preosteoblasts toward future bone formation sites observed in the early stage of intramembranous osteogenesis is a critical cellular process for normal bone formation. However, molecular biological mechanisms of the chemotaxis of preosteoblasts are not fully understood. We have recently clarified, for the first time, the critical role of the cellular communication network factor 2 (CCN2)/connective tissue growth factor (CTGF)-integrin α5-Ras axis for chemotaxis of preosteoblasts during new bone formation through intramembranous osteogenesis. In this chapter, we describe in detail the procedures of the in vivo and in vitro assays to investigate the chemotactic property of CCN2/CTGF and its underlying molecular biological mechanisms during intramembranous osteogenesis.


Assuntos
Fator de Crescimento do Tecido Conjuntivo , Osteogênese , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Osteogênese/fisiologia , Quimiotaxia
10.
Interv Cardiol Clin ; 12(1): 21-29, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36372459

RESUMO

Fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs) provide an important clinical tool to evaluate the hemodynamic significance of coronary lesions. However, these indices have major limitations. As these indices are meant to be surrogates of coronary flow, clinical scenarios such as aortic stenosis (with increased end-systolic and end-diastolic pressures) or atrial fibrillation (with significant beat-to-beat cardiac output variability) can have significant effect on the accuracy and reliability of these hemodynamic indices. Here, we provide a comprehensive evaluation of the pitfalls, limitations, and strengths of FFR and NHPRs in common clinical scenarios paired with coronary artery disease.


Assuntos
Estenose da Valva Aórtica , Fibrilação Atrial , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Humanos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Angiografia Coronária , Vasos Coronários , Hipertrofia Ventricular Esquerda/diagnóstico , Fibrilação Atrial/complicações , Cateterismo Cardíaco , Reprodutibilidade dos Testes , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia
11.
Interv Cardiol Clin ; 12(1): 95-117, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36372465

RESUMO

Coronary computed tomography angiography (CCTA) and CCTA-derived fractional flow reserve (FFRCT) are the best non-invasive techniques to assess coronary artery disease (CAD) and myocardial ischemia. Advances in these technologies allow a paradigm shift to the use of CCTA and FFRCT for advanced plaque characterization and planning myocardial revascularization.


Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Humanos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Angiografia Coronária/métodos , Angiografia por Tomografia Computadorizada/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Revascularização Miocárdica
12.
Interv Cardiol Clin ; 12(1): 1-12, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36372454

RESUMO

Despite the now routine integration of invasive physiologic systems into coronary catheter laboratories worldwide, it remains critical that all operators maintain a sound understanding of the fundamental physiologic basis for coronary pressure assessment. More specifically, performing operators should be well informed regarding the basis for hyperemic (ie, fractional flow reserve) and nonhyperemic (ie, instantaneous wave-free ratio and other nonhyperemic pressure ratio) coronary pressure assessment. In this article, we provide readers a comprehensive history charting the inception, development, and validation of hyperemic and nonhyperemic coronary pressure assessment.


Assuntos
Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Hiperemia , Humanos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Cateterismo Cardíaco , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Hiperemia/diagnóstico
13.
Interv Cardiol Clin ; 12(1): 119-129, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36372455

RESUMO

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.


Assuntos
Doença da Artéria Coronariana , Angina Microvascular , Adulto , Humanos , Microcirculação/fisiologia , Doença da Artéria Coronariana/diagnóstico , Angina Microvascular/diagnóstico , Angina Microvascular/terapia , Angiografia Coronária
14.
Interv Cardiol Clin ; 12(1): 41-53, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36372461

RESUMO

Modern coronary intervention requires integration of angiographic, physiologic, and intravascular imaging. This article describes the use and techniques needed to understand coronary physiology pullback data and how use it to make revascularization decisions. The article describes instantaneous wave-free ratio, fractional flow reserve, and the data that support their use and how they differ when used in tandem disease. Common practical mistakes and errors are discussed together with a brief review of the limited published research data.


Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Humanos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Cateterismo Cardíaco/métodos , Valor Preditivo dos Testes
15.
Interv Cardiol Clin ; 12(1): 55-69, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36372462

RESUMO

Coronary physiologic assessment has become a standard of care for patients with coronary atherosclerotic disease. While most attention has focused on pre-interventional physiologic assessment to aid in revascularization decision-making, post-interventional physiologic assessment has not been as widely used, despite evidence supporting its role in assessment and optimization of the revascularization procedure. A thorough understanding of such evidence and ongoing studies would be crucial to incorporate post-interventional physiologic assessment into daily practice. Thus, this review provides a comprehensive overview of current evidence regarding the evolving role of physiologic assessment as a functional optimization tool for the entire revascularization process.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Humanos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Angiografia Coronária , Intervenção Coronária Percutânea/métodos , Doença da Artéria Coronariana/cirurgia
16.
Carbohydr Polym ; 300: 120237, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36372504

RESUMO

The effects of dietary chitosan (0, 2, 4, 6, 8 and 10 g/kg) on the growth, health condition and disease resistance of golden pompano Trachinotus ovatus were evaluated. Dietary chitosan significantly enhanced weight gain, with the highest observed in fish fed the 6 g/kg chitosan diet. This chitosan level significantly promoted gut health by increasing villus length, lipase and protease activities and intestinal barrier-related genes expression. Meanwhile, dietary 6 g/kg chitosan improved the inflammatory response and anti-oxidative capacity of fish by regulating the expression of genes involved in NF-κB pathway and Nrf2 pathway, respectively. Furthermore, after challenge with Vibrio harveyi for 2 weeks, the survival rate increased significantly when dietary chitosan level was 6 g/kg. Overall, our results indicate that 6 g/kg chitosan is the optimal dose for enhancing growth, health and disease resistance of fish, but excessive chitosan (10 g/kg) weakens its beneficial effects.


Assuntos
Quitosana , Doenças dos Peixes , Perciformes , Vibrioses , Animais , Resistência à Doença , Quitosana/farmacologia , Perciformes/fisiologia , Ração Animal/análise , Doenças dos Peixes/tratamento farmacológico , Suplementos Nutricionais , Dieta , Peixes , Nível de Saúde , Imunidade Inata
17.
Methods Mol Biol ; 2597: 59-75, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36374414

RESUMO

At the moment, many researchers are using in vitro techniques to investigate chemokine-driven leukocyte adhesion/recruitment, for example, by using a transwell or flow chamber system. Here we describe a more physiologically relevant, sophisticated, and highly flexible method to study leukocyte adhesion ex vivo in fresh murine carotid arteries under arterial flow conditions. This model mimics an in vivo situation and allows the combination of leukocytes and arteries isolated from different donors in one experiment, generating information on both vascular and leukocyte adhesive properties of both donors. This method provides a versatile, highly physiologically relevant model to investigate leukocyte adhesion.


Assuntos
Quimiocinas , Leucócitos , Camundongos , Animais , Adesão Celular/fisiologia , Leucócitos/fisiologia , Artérias Carótidas , Perfusão , Endotélio Vascular/fisiologia
18.
J Environ Sci (China) ; 125: 750-760, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375957

RESUMO

Copper (Cu) is a kind of micronutrient element that is essential for human metabolism. However, it is also considered as an environmental pollutant which is toxic to organisms at a high concentration level. Probiotics, regarded as beneficial microorganisms for promoting human health, have functions of antioxidant capacity, immune-enhancing properties, intestinal barrier protection and regulation. Several studies have reported that probiotics show positive effects on alleviating and intervening heavy metals toxicity. However, evidence for relieving copper-induced toxicity by probiotics is still limited. In this study, we firstly conducted a zebrafish larvae model to screen out microorganisms which are helpful for CuSO4 toxicity resistance and one novel strain named as Bacillus coagulans XY2 was discovered with the best protective activity. B. coagulans XY2 significantly reduced the mortality of zebrafish larvae exposed to 10 µmol/L CuSO4 for 96 hr, as well as alleviated the neutrophils infiltration in the larvae lateral line under a 2 hr exposure. B. coagulans XY2 exhibited a high in vitro antioxidant activity and against CuSO4-induced oxidative stress in zebrafish larvae by up-regulating sod1, gstp1 and cat gene transcriptional levels and relevant enzymatic activities. CuSO4 stimulated the inflammation process resulting in obvious increases of gene il-1ß and il-10 transcription, which were suppressed by B. coagulans XY2 intervention. Overall, our results underline the bio-function of B. coagulans XY2 on protecting zebrafish larvae from copper toxicity, suggesting the potential application values of probiotics in copper toxicity alleviation on human and the environment.


Assuntos
Bacillus coagulans , Probióticos , Humanos , Animais , Bacillus coagulans/fisiologia , Peixe-Zebra , Cobre/toxicidade , Cobre/metabolismo , Larva , Antioxidantes/metabolismo
19.
Behav Brain Res ; 437: 114146, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36202146

RESUMO

Some diabetes patients develop depression, the main treatment for which is antidepressants. Pharmacological interactions between insulin and antidepressants (e.g., fluoxetine) are controversial in the literature. Some authors reported hypoglycemic actions of fluoxetine, whereas others reported antidepressant-like actions. In healthy rats, insulin produces an antidespair-like action in rats through an increase in locomotor and exploratory activity, but differences in actions of insulin and fluoxetine on neuronal activity are unknown. The present study evaluated Wistar healthy rats that were treated with saline, insulin, fluoxetine, or fluoxetine + insulin for 3 days (short-term) or 21 days (long-term). The model consisted of electrical stimulation of the lateral septal nucleus (LSN) while we performed single-unit extracellular response recordings in the prelimbic cortex (PL) and infralimbic cortex (IL) subregions of the medial prefrontal cortex (mPFC). Stimulation of the LSN produced an initial brief excitatory paucisynaptic response and then a long-lasting inhibitory afterdischarge in the PL and IL. Treatment with saline and fluoxetine, but not insulin, minimally affected the paucisynaptic response. Differences were found in LSN-IL responsivity. The inhibitory afterdischarge was clearly enhanced in the long-term fluoxetine group but not by insulin alone or fluoxetine + insulin. These findings suggest that insulin produces some actions that are opposite to fluoxetine on LSN-mPFC connection responsivity, with no synergistic actions between the actions of insulin and fluoxetine.


Assuntos
Núcleos Septais , Animais , Ratos , Fluoxetina/farmacologia , Insulina/farmacologia , Ratos Wistar , Córtex Pré-Frontal/fisiologia , Antidepressivos/farmacologia
20.
Behav Brain Res ; 437: 114145, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36206819

RESUMO

Behavioral flexibility (or set-shifting), which is regulated by the prefrontal cortex (PFC), is often impaired in patients with attention-deficit/hyperactivity disorder (ADHD), which is characterized by poor inhibitory control and reinforcement learning. Transcranial direct current stimulation (tDCS) has been proposed as a means of noninvasive brain stimulation and a potential therapeutic tool for modulating behavioral flexibility. Animal studies can pave the way to know if tDCS application can potentially benefit rule- and goal-based activities in ADHD. Spontaneously hypertensive rats (SHRs) and inbred Wistar-Kyoto (WKY) rats were used as an animal model of ADHD and controls, respectively, and their strategy set-shifting abilities, including initial discrimination, set-shifting, and reversal learning tasks under 0-s or 15-s reinforcer delivery delay conditions, were evaluated. The tDCS treatment had a limited effect on the performance of the SHRs and WKY rats in initial discrimination task under 0-s delay condition. Under the 15-s delay condition, the SHRs had longer lever-press reaction times and/or more trial omissions than the WKY rats did when completing set-shifting and reversal-learning tasks. Among the SHRs, tDCS treatment improved the rats' reaction times and/or reduced their trial omissions in the set-shifting and reversal-learning tasks. Although tDCS may improve delayed reinforcement learning set-shifting performance in SHRs, further studies are required to clarify the responsible mechanism.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulação Transcraniana por Corrente Contínua , Animais , Ratos , Ratos Endogâmicos WKY , Atenção/fisiologia , Ratos Endogâmicos SHR , Modelos Animais de Doenças
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