Dopamine is involved in physiological processes like learning and memory, motor control and reward, and pathological conditions such as Parkinson’s disease and addiction. In contrast to the extensive ...studies on neurons, astrocyte involvement in dopaminergic signaling remains largely unknown. Using transgenic mice, optogenetics, and pharmacogenetics, we studied the role of astrocytes on the dopaminergic system. We show that in freely behaving mice, astrocytes in the nucleus accumbens (NAc), a key reward center in the brain, respond with Ca2+ elevations to synaptically released dopamine, a phenomenon enhanced by amphetamine. In brain slices, synaptically released dopamine increases astrocyte Ca2+, stimulates ATP/adenosine release, and depresses excitatory synaptic transmission through activation of presynaptic A1 receptors. Amphetamine depresses neurotransmission through stimulation of astrocytes and the consequent A1 receptor activation. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the dopamine- and amphetamine-induced synaptic regulation, revealing a novel cellular pathway in the brain reward system.
•Astrocytes in the Nucleus Accumbens respond to synaptic dopamine in vivo•Astrocytes mediate the synaptic regulation induced by dopamine and amphetamine•Amphetamine-induced enhancement in locomotion activity is modulated by astrocytes
Corkrum et al. report that astrocyte activity is required for dopamine- and amphetamine-evoked synaptic regulation and amphetamine-induced locomotor effects. Their study reveals astrocytes as active components of dopaminergic signaling and the brain reward system.
Interneurons are critical for proper neural network function and can activate Ca
signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation ...remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition
potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABA
receptors, potentiation involved astrocyte GABA
receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABA
receptor (
) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.
Adenosine and uric acid (UA) play a pivotal role in lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). In the present experiments, we measured adenosine synthesis from ...nicotinamide adenine dinucleotide (NAD
) in membranes prepared from wild type (WT) and CD38 knockout (CD38KO) mouse lungs, from cultured airway smooth muscle and epithelial cells, and in bronchoalveolar lavage fluid after airway challenge with epidemiologically relevant allergens. Adenosine was determined using an enzymatically coupled assay that produces ATP and is detected by luminescence. Uric acid was determined by ELISA. Exposure of cultured airway epithelial cells to
extract caused significant nucleotide (NAD
and ATP) release in the culture media. The addition of NAD
to membranes prepared from WT mice resulted in faster generation of adenosine compared to membranes from CD38KO mice. Formation of adenosine from NAD
affected UA and ATP concentrations, its main downstream molecules. Furthermore, NAD
and adenosine concentrations in the bronchoalveolar lavage fluid decreased significantly following airway challenge with house-dust mite extract in WT but not in CD38KO mice. Thus, NAD
is a significant source of adenosine and UA in the airways in mouse models of allergic airway disease, and the capacity for their generation from NAD
is augmented by CD38, a major NADase with high affinity for NAD
. This novel non-canonical NAD
-adenosine-UA pathway that is triggered by allergens has not been previously described in the airways.
Mice carrying bacterial artificial chromosome (BAC) transgenes have become important tools for neuroscientists, providing a powerful means of dissecting complex neural circuits in the brain. ...Recently, it was reported that one popular line of these mice--mice possessing a BAC transgene with a D(2) dopamine receptor (Drd2) promoter construct coupled to an enhanced green fluorescent protein (eGFP) reporter--had abnormal striatal gene expression, physiology, and motor behavior. Unlike most of the work using BAC mice, this interesting study relied upon mice backcrossed on the outbred Swiss Webster (SW) strain that were homozygous for the Drd2-eGFP BAC transgene. The experiments reported here were conducted to determine whether mouse strain or zygosity was a factor in the reported abnormalities. As reported, SW mice were very sensitive to transgene expression. However, in more commonly used inbred strains of mice (C57BL/6, FVB/N) that were hemizygous for the transgene, the Drd2-eGFP BAC transgene did not alter striatal gene expression, physiology, or motor behavior. Thus, the use of inbred strains of mice that are hemizygous for the Drd2 BAC transgene provides a reliable tool for studying basal ganglia function.
Salud familiar en niños con discapacidad intelectual Palacio Sheryz, Madai; Delgado Gonzales, Orlando; Forment Poutou, Susel ...
Revista información científica,
2020, 2020-01-01, Volume:
99, Issue:
1
Journal Article
Peer reviewed
Open access
Introduction: the family's transit through the stages of the life cycle has events that boost family functionality, having a child diagnosed with intellectual disability breaks the dynamic.Objective: ...to diagnose the health of the family member where an intellectual disabled person belonging to the Special School "José Antonio Echavarría" of the Guantánamo municipality lives.Method: a descriptive study of a quantitative cross-sectional study was carried out in 45 families of the “José Antonio Echavarría” Special School of the Guantánamo municipality. The theoretical-methodological model of family health evaluation was used, which included as evaluation instruments, the proof of perception of family functioning, inventory of family risk characteristics and the family matrix.Results: according to the ontogenesis of the families, the ones extended by 65.3% predominated, by the composition and structure, the medium ones, and by the number of three-generational generations, for 45.36%. The paranormative crises were present in 66.6% of the families when presenting dismemberment, 39.8% due to demoralization, only 4.4% of the families were functional. According to family risk characteristics, the variables that prevailed most were critical regulatory processes with 95.5%, critical health processes and paranormal regulatory processes for 100%. The crossing of the results gave rise to the family health matrix.Conclusions: it was revealed that the presence of a disabled child is more frequent in dysfunctional families, which more commonly do not fulfill their functions.
Introdução: o trânsito da família pelas etapas do ciclo de vida tem eventos que aumentam a funcionalidade da família, tendo um filho com diagnóstico de deficiência intelectual rompe a dinâmica.Objetivo: diagnosticar a saúde do familiar onde mora uma pessoa com deficiência intelectual pertencente à Escola Especial "José Antonio Echavarría", do município de Guantánamo.Método: foi realizado um estudo descritivo de um estudo transversal quantitativo em 45 famílias da Escola Especial “José Antonio Echavarría” do município de Guantánamo. Utilizou-se o modelo teórico-metodológico de avaliação em saúde da família, que incluiu como instrumentos de avaliação, a prova de percepção do funcionamento da família, inventário das características de risco familiar e matriz familiar.Resultados: de acordo com a ontogênese das famílias, as ampliadas em 65,3% predominaram, pela composição e estrutura, as médias e pelo número de três gerações geracionais, para 45,36%. As crises paranormativas estavam presentes em 66,6% das famílias quando apresentavam desmembramento, 39,8% devido à desmoralização, apenas 4,4% das famílias eram funcionais. De acordo com as características de risco familiar, as variáveis que mais prevaleceram foram processos regulatórios críticos com 95,5%, processos críticos de saúde e processos reguladores paranormais para 100%. O cruzamento dos resultados deu origem à matriz de saúde da família.Conclusões: foi revelado que a presença de uma criança com deficiência é mais frequente em famílias disfuncionais, que mais comumente não cumprem suas funções.
Introducción: el tránsito de la familia por las etapas de ciclo vital tiene eventos que dinamizan la funcionabilidad familiar, tener un hijo diagnosticado con discapacidad intelectual irrumpe la dinámica.Objetivo: diagnosticar la salud del familiar donde convive un discapacitado intelectual perteneciente a la Escuela Especial “José Antonio Echavarría” del municipio Guantánamo.Método: se realizó un estudio descriptivo de corte transversal cuanticualitativo, en 45 familias de la Escuela Especial “José Antonio Echavarría” del municipio Guantánamo. Se utilizó el modelo teórico-metodológico de evaluación de la salud familiar que incluyó como instrumentos de evaluación, la prueba de percepción del funcionamiento familiar, inventario de características familiares de riesgo y la matriz familiar.Resultados: según la ontogénesis de las familias predominaron las ampliadas para un 65,3 %, por la composición y estructura, las medianas, y por el número de generaciones trigeneracional, para un 45,36 %. Las crisis paranormativas estaban presentes en 66,6 % de las familias al presentar desmembramiento, el 39,8 % por desmoralización, sólo el 4,4 % de las familias fue funcional. Según características familiares de riesgo las variables que más prevalecieron fueron procesos críticos normativos con un 95,5 %, procesos críticos de salud y procesos críticos paranormativos para un 100 %. El cruzamiento de los resultados dió lugar a la matriz de salud familiar.Conclusiones: se reveló que es más frecuente la presencia de un niño discapacitado en familias disfuncionales, que de manera más común no satisfacen sus funciones.
While experimental evidence suggests potential carcinogenic effects of increased iron load, there is a lack of data on iron status and cancer risk from epidemiological studies. Here, we evaluated ...prediagnostic serum concentrations of ferritin, iron and transferrin as well as transferrin saturation (TSAT) in relation to cancer risk and mortality in a prospective study by multivariable Cox regression analyses. A case–cohort sample of the population‐based EPIC‐Heidelberg Study including a random subcohort (n = 2738) and incident cases of breast cancer (n = 627), prostate cancer (n = 554), lung cancer (n = 195), colorectal cancer (n = 256) and cancer death (n = 759) was used. Ferritin levels were inversely associated with breast cancer risk in the multivariable Cox regression model, with a hazard ratio (HR) of 0.67 95% confidence interval: 0.49, 0.92 for women in the highest quartile compared to those in the lowest quartile. Neither ferritin nor the other markers of iron status were significantly associated with colorectal, prostate or lung cancer risk. An inverse association was observed between ferritin and total cancer mortality (HR: 0.70 0.53, 0.92). There were no significant overall associations between serum iron, transferrin or TSAT and cancer mortality. The present findings do not support the notion of increased iron load constituting a cancer risk factor in the general population. By contrast, our analyses revealed inverse associations between ferritin levels and breast cancer risk as well as cancer mortality.
What's new?
While experimental evidence suggests carcinogenic effects of increased iron load, there is a lack of data on iron status and cancer risk from epidemiological studies. Here, the authors evaluated associations between prediagnostic serum levels of ferritin, serum iron, transferrin and transferrin saturation and the risk of common cancers using a large case–cohort sample. The established biomarkers of iron status were not associated with increased cancer risk. By contrast, higher serum ferritin was related to lower risks of breast cancer and cancer mortality. The findings suggest that higher iron load does not constitute a cancer risk factor in the general population.
High iron load and red meat consumption could increase the risk of cardiovascular diseases (CVDs). As red meat is the main source of heme iron, which is in turn a major determinant of increased iron ...load, adverse cardiometabolic effects of meat consumption could be mediated by increased iron load.
The object of the study was to assess whether associations between red meat consumption and CVD risk are mediated by iron load in a population-based human study.
We evaluated relations between red meat consumption, iron load (plasma ferritin), and risk of CVD in the prospective EPIC-Heidelberg Study using a case-cohort sample including a random subcohort (n = 2738) and incident cases of myocardial infarction (MI, n = 555), stroke (n = 513), and CVD mortality (n = 381). Following a 4-step mediation analysis, associations between red meat consumption and iron load, red meat consumption and CVD risk, and iron load and CVD risk were assessed by multivariable regression models before finally testing to which degree associations between red meat consumption and CVD risk were attenuated by adjustment for iron status.
Red meat consumption was significantly positively associated with ferritin concentrations and MI risk HR per 50 g daily intake: 1.18 (95% CI: 1.05, 1.33), but no significant associations with stroke risk and CVD mortality were observed. While direct associations between ferritin concentrations and MI risk as well as CVD mortality were significant in age- and sex-adjusted Cox regression models, these associations were substantially attenuated and no longer significant after multivariable adjustment for classical CVD risk factors. Strikingly, ferritin concentrations were positively associated with a majority of classical CVD risk factors (age, male sex, alcohol intake, obesity, inflammation, and lower education).
Increased ferritin concentrations may be a marker of an overall unfavorable risk factor profile rather than a mediator of greater CVD risk due to meat consumption.
Musical performance is a skilled activity performed under intense pressure, thus is often a profound source of anxiety. In other contexts, anxiety and its concomitant symptoms of sympathetic nervous ...system arousal have been successfully ameliorated with HRV biofeedback (HRV BF), a technique involving slow breathing which augments autonomic and emotional regulatory capacity.
This randomised-controlled study explored the impact of a single 30-minute session of HRV BF on anxiety in response to a highly stressful music performance.
A total of 46 trained musicians participated in this study and were randomly allocated to a slow breathing with or without biofeedback or no-treatment control group. A 3 Group×2 Time mixed experimental design was employed to compare the effect of group before and after intervention on performance anxiety (STAI-S) and frequency domain measures of HRV.
Slow breathing groups (n=30) showed significantly greater improvements in high frequency (HF) and LF/HF ratio measures of HRV relative to control (n=15) during 5 minute recordings of performance anticipation following the intervention (effect size: η(2) =0.122 and η(2) =0.116, respectively). The addition of biofeedback to a slow breathing protocol did not produce differential results. While intervention groups did not exhibit an overall reduction in self-reported anxiety, participants with high baseline anxiety who received the intervention (n=15) displayed greater reductions in self-reported state anxiety relative to those in the control condition (n=7) (r=0.379).
These findings indicate that a single session of slow breathing, regardless of biofeedback, is sufficient for controlling physiological arousal in anticipation of psychosocial stress associated with music performance and that slow breathing is particularly helpful for musicians with high levels of anxiety. Future research is needed to further examine the effects of HRV BF as a low-cost, non-pharmacological treatment for music performance anxiety.
COVID-19: from epidemiology to treatment Pericàs, J M; Hernandez-Meneses, M; Sheahan, T P ...
European heart journal,
06/2020, Volume:
41, Issue:
22
Journal Article
Peer reviewed
Open access
Abstract
The COVID-19 pandemic has greatly impacted the daily clinical practice of cardiologists and cardiovascular surgeons. Preparedness of health workers and health services is crucial to tackle ...the enormous challenge posed by SARS-CoV-2 in wards, operating theatres, intensive care units, and interventionist laboratories. This Clinical Review provides an overview of COVID-19 and focuses on relevant aspects on prevention and management for specialists within the cardiovascular field.
Girls and boys might differ in autistic symptoms and associated cognitive difficulties such as executive function (EF). We investigated sex differences in the relationship between parent rated EF and ...autistic symptoms in 116 children and adolescents (25 girls) aged 5–19 years with an intelligence quotient above 70 and an autism spectrum disorder (ASD) diagnosis. They were rated with the behavior rating inventory of executive function (BRIEF) and the autism diagnostic interview revised (ADI-R). We found a positive association between EF and the ADI-R domains of reciprocal social interaction (
p
< 0.001) and communication (
p
= 0.001) in girls, while these relationships were small and non-significant in boys. Our results provide a greater understanding of the sex-specific characteristics of children and adolescents with ASD.
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