ABSTRACT
The nucleus accumbens (nAc) is a critical region in the brain reward system since it integrates abundant synaptic inputs contributing to the control of neuronal excitability in the circuit. The presence of inhibitory α1 glycine receptor (GlyRs) subunits, sensitive to ethanol, has been recently reported in accumbal neurons suggesting that they are protective against excessive binge consumption. In the present study, we used viral vectors (AAV) to overexpress mutant and WT α1 subunits in accumbal neurons in D1 Cre and α1 KI mice. Injection of a Cre-inducible AAV carrying an ethanol insensitive α1 subunit in D1 Cre neurons was unable to affect sensitivity to ethanol in GlyRs or affect ethanol drinking. On the other hand, using an AAV that transduced WT α1 GlyRs in GABAergic neurons in the nAc of high-ethanol consuming mice caused a reduction in ethanol intake as reflected by lowered drinking in the dark and reduced blood ethanol concentration. As expected, the AAV increased the glycine current density by 5-fold without changing the expression of GABAA receptors. Examination of the ethanol sensitivity in isolated accumbal neurons indicated that the GlyRs phenotype changed from an ethanol resistant to an ethanol sensitive type. These results support the conclusion that increased inhibition in the nAc can control excessive ethanol consumption and that selective targeting of GlyRs by pharmacotherapy might provide a mechanistic procedure to reduce ethanol binge.
Subject(s)
Binge Drinking , Glycine , Animals , Mice , Binge Drinking/genetics , Binge Drinking/metabolism , Ethanol/pharmacology , GABAergic Neurons/metabolism , Glycine/pharmacology , Glycine/metabolism , Nucleus Accumbens/metabolism , Receptors, Glycine/genetics , Receptors, Glycine/metabolismABSTRACT
El estudio analiza las condiciones nutricionales, desarrollo madurativo y el estado emocional en niños/as y adolescentes (NNA) de comunidades ecuatorianas de minería artesanal; en comparación con NNA de comunidades ubicadas en la zona de influencia del proyecto megaminero "Fruta del Norte", concesionado a la multinacional Kinross Aurelian, actualmente en fase de exploración avanzada1. Se realizó un diseño no experimental de tipo analítico que fue aplicado al universo de las poblaciones seleccionadas. La investigación se estructuró en dos componentes, el primero caracterizó a las comunidades de pequeña minería y megaminería, determinando los patrones diferenciales de exposición, para esto se utilizó una entrevista semi estructurada aplicada durante asamblea en cada comunidad de estudio. Por otro lado, se aplicó una evaluación antropométrica y los Test Visomotor de Bender y Sacks, a todos los NNA de las comunidades seleccionadas. Si bien, no se encontraron diferencias significativas en las condiciones nutricionales, la investigación revela una diferencia importante en la presencia de desajustes emocionales y retrasos en el desarrollo evolutivo en los NNA de las comunidades cercanas al proyecto megaminero, concluyendo que las condiciones de ruptura del tejido social y el incremento de conflictos comunitarios atribuidos a la presencia de la multinacional, son determinantes de los impactos en salud.
The study proposes an analysis of the nutritional conditions, maturity development and the emotional state of the children and adolescents (NNA) that live in Ecuadorian communities of artisanal mining; in comparison with the children and adolescents of the communities located in the area of influence of the mega mining project "Fruta del Norte", managed by the multinational Kinross-Aurelian. This project is currently in the phase of 'advanced exploration'. A non-experimental analytic design was applied to the universe of selected populations. The research was divided into two components. The first component characterized by small mining communities in comparison with a big scale mining communities determining differential patterns of exposure through a semi structured interview applied during an assembly in each community. The second component used an anthropometric evaluation, Bender visualmotor tests and Sacks test, to evaluate all of the NNA at the selected communities. While not significant differences were found in the nutritional conditions, an increase of emotional disorders and evolutionary developmental deficiencies among the children and adolescents of the communities close to the mega mining project. The research concludes that the conditions of the social tissue rupture and the increases of community conflicts which were attributed to the presence of the multinational are determinants of health impacts
Subject(s)
Humans , Male , Female , Child , Adolescent , Stress, Psychological , Child , Nutritional Status , Residence Characteristics , Diagnosis of Health Situation in Specific Groups , Mental HealthABSTRACT
The northeastern Ecuadorian border has undergone aerial spraying with an herbicide mix that contains surfactants and adjuvants, executed by the Colombian Government. The purpose of this study was to diagnose social, health, and genetic aspects of the people affected by glyphosate. For this objective to be achieved, 144 people were interviewed, and 521 medical diagnoses and 182 peripheral blood samples were obtained. Genotyping of GSTP1 Ile105Val, GPX-1 Pro198Leu, and XRCC1 Arg399Gln polymorphisms were analyzed, using PCR-RFLP technique. The assessment of chromosomal aberrations was performed, obtaining 182 karyotypes. Malnutrition in children was 3%. Of the total population, 7.7% had children with malformations, and the percentage of abortions was 12.7%. Concerning genotyping, individuals with GSTP1 Val/Val obtained an odds ratio of 4.88 (p < 0.001), and Ile/Val individuals, together with Val/Val individuals, had an odds ratio of 2.6 (p < 0.05). In addition, GPX-1 Leu/Leu individuals presented an odds ratio (OR) of 8.5 (p < 0.05). Regarding karyotyping, the 182 individuals had normal karyotypes. In conclusion, the study population did not present significant chromosomal and DNA alterations. The most important social impact was fear. We recommend future prospective studies to assess the communities.
