Increased stress vulnerability in the offspring of socially isolated rats: Behavioural, neurochemical and redox dysfunctions.

Stressful events during pregnancy impact on the progeny neurodevelopment. However, little is known about preconceptional stress effects. The rat social isolation represents an animal model of chronic stress inducing a variety of dysfunctions. Moreover, social deprivation during adolescence interferes with key neurodevelopmental processes. Here, we investigated the development of behavioural, neurochemical and redox alterations in the male offspring of socially isolated female rats before pregnancy, reared in group (GRP) or in social isolation (ISO) from weaning until young-adulthood. To this aim, females were reared in GRP or in ISO conditions, from PND21 to PND70, when they were mated. Their male offspring was housed in GRP or ISO conditions through adolescence and until PND70, when passive avoidance-PA, novel object recognition-NOR and open field-OF tests were performed. Levels of noradrenaline (NA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), glutamate (GLU) and GABA were assessed in the prefrontal cortex (PFC). Moreover, cortical ROS levels were quantified, as well as NF-kB and the NADPH oxidase NOX2 expression, redox status (expressed as GSH:GSSG ratio) and SOD1 amount. A significant decrease of the latency time in the PA was observed in the offspring of ISO females. In the NOR test, while a significant increase in the exploratory activity towards the novel object was observed in the offspring of GRP females, no significant differences were found in the offspring of ISO females. No significant differences were found in the OF test among experimental groups. Theoffspring of ISO females showed increased NA and 5-HIAA levels, whereas in the offspring persistently housed in isolation condition from weaninguntil adulthood, we detected reduced 5-HT levels and ehnanced 5-HIAA amount. No significant changes in GLU concentrations were detected, while decreased GABA content was observed in the offspring of ISO females exposed to social isolation. Increased ROS levels as well as reduced NF-κB, NOX2 expression were detected in the offspring of ISO females. This was accompanied by reduced redox status and enhanced SOD1 levels. In conclusion, our results suggest that female exposure to chronic social stress before pregnancy might have a profound influence on the offspring neurodevelopment in terms of cognitive, neurochemical and redox-related alterations, identifying this specific time window for possible preventive and therapeutic strategies.

Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism.

Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T+ Itpr3tf/J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala.

Sobrepeso, obesidad y niveles de presión arterial en niños de nivel 5 de jardines de infantes públicos de Montevideo: prevalencia y factores asociados / Overweight, obesity and high-blood pressure in 5 year-old children in 5 public preschool centers in Montevideo: prevalence and associated factors / Sobrepeso, obesidade e níveis de pressão arterial em crianças de nível 5 de jardins de infância públicos de Montevidéu: prevalência e fatores associados

Resumen: Introducción: en Uruguay, en los últimos años, se ha constatado un incremento en la prevalencia de sobrepeso y obesidad. La evidencia científica ha demostrado que las condiciones en la primera infancia son determinantes. Objetivo: determinar la prevalencia de sobrepeso, obesidad y los niveles de presión arterial (PA) braquial e identificar factores de riesgo asociados en niños de nivel 5 que concurren a jardines públicos de Montevideo. Método: estudio transversal (7/2016-6/2017) en una muestra representativa de 771 niños de nivel 5 de jardines públicos de Montevideo. Se relevó historia y comportamiento alimentario, actividad física, hábitos de sueño, peso y talla materna. En cada niño se registró antropometría y PA braquial. Resultados: la prevalencia de sobrepeso u obesidad fue 40,6% (IC95%: 37,4-44,3), obesidad 16,5% (IC95%: 13,9-19,1) y obesidad abdominal 12,9% (IC95%: 11,0-15,8). Reportaron sobrepeso 29,4% de las madres y obesidad 21,9%. Se observó sedentarismo en 58,3%, exposición prolongada a pantallas en 60,4% y escasas horas de sueño en 40,9%. El consumo frecuente de alfajores, obleas y bizcochos en el desayuno, de embutidos entre semana, la preferencia de alimentos con publicidad, y el reporte de sobrepeso u obesidad materna se asociaron con obesidad infantil. Los niños con sobrepeso, obesidad u obesidad abdominal presentaron mayores niveles de PA braquial. Conclusiones: la prevalencia de sobrepeso y obesidad en niños de nivel 5 de jardines públicos de Montevideo es elevada. El sobrepeso, la obesidad materna y los hábitos en relación con la alimentación, actividad física y sueño se asocian con su presencia.

Summary: Introduction: in recent years, Uruguay has seen an increase of the prevalence of overweight and obesity. Scientific evidence has shown that early childhood conditions are determinant. Objective: to determine the prevalence of overweight, obesity and brachial blood pressure levels and identify associated risk factors in 5-year-old children who attend public preschool centers in Montevideo. Method: transversal study (7/2016-6/2017) in a representative sample of 771 5-year-old children from preschool centers in Montevideo. We assessed their history, eating habits, physical activity, sleeping habits, weight and maternal size. We recorded anthropometry and brachial blood pressure for each child. Results: the prevalence of overweight or obesity was 40.6% (CI 95%: 37.4- 44.3), obesity 16.5% (CI 95%: 13.9-19.1) and abdominal obesity 12.9% (CI 95%: 11.0-15.8). 29.4% of mothers reported overweight and 21.9% of them reported obesity. Sedentary lifestyle was found in 58.3%, long screen viewing in 60.4% and inadequate sleep in 40.9%. Frequent consumption of pastries, wafers and biscuits for breakfast, cold cuts during week days, preference of food they see in advertisements, and reported maternal overweight or obesity were associated to child obesity. Children with overweight and/or abdominal obesity evidenced higher levels of brachial blood pressure. Conclusions: prevalence of overweight and obesity in 5-year-old children from public preschool centers in Montevideo is high. Maternal overweight and obesity and habits in connection with eating, physical activity and amount of sleep are associated with this condition.

Resumo: Introdução: nos últimos anos observou-se um aumento da prevalência de sobrepeso e obesidade no Uruguai. A evidência científica mostra que as condições de vida na primeira infância são determinantes. Objetivo: determinar a prevalência de sobrepeso, obesidade e os niveles de pressão arterial (PA) braquial e identificar fatores de risco associados em crianças com 5 anos que frequentam jardines de infância públicos em Montevidéu. Métodos: estudo transversal (7/2016-6/2017) em uma amostra representativa de 771 crianças com 5 anos de jardins de infância públicos de Montevidéu. Foram coletados dados sobre a história e o comportamento alimentar, atividade física, hábitos de sono e peso e altura materna. Os dados antropométricos e PA braquial de todas as crianças foram registrados. Resultados: a prevalência de sobrepeso ou obesidade foi de 40,6% (I.C.95%:37,4-44,3), obesidade 16,5% (I.C.95%:13,9-19,1) e obesidade abdominal 12,9% (I.C.95%:11,0-15,8). 29,4% das mães informaram sobrepeso e 21,9% obesidade. Observou-se sedentarismo em 58,3%, exposição prolongada a telas de equipamentos eletrônicos em 60,4% e poucas horas de sono em 40,9%. O consumo frequente de alfajores, obleias e pães com altos teores de açúcar e gordura no café da manhã, de embutidos nos dias de semana, preferência de alimentos com publicidade, e a informação de sobrepeso ou obesidade materna estava associado a obesidade infantil. As crianças com sobrepeso, obesidade e/ou obesidade abdominal apresentaram niveles mais altos de PA braquial. Conclusões: a prevalência de sobrepeso e obesidade em crianças com 5anos de jardins de infância públicos de Montevidéu é elevada. O sobrepeso e obesidade materna e os hábitos relacionados à alimentação, atividade física e sono, estão associados à sua presença.

1er. Censo Nacional de Talla en niños de 1er. grado escolar / 1st. National Census of Height in first grade school children

El 1er. Censo Nacional de Talla de los niños de 1er. grado escolar en la República Oriental del Uruguay ha significado un instrumento valioso para orientar el proceso de planificación en el campo de la Alimentación y Nutrición. Dada la elevada cobertura del sistema escolar, ha sido posible contar con información con una importante desagregación espacial. El porcentaje de niños con Retraso de Talla (R:T:) por área geográfica ha mostrado una alta correlación con el porcentaje de hogares con Necesidades Básicas Insatisfechas (N.B.I.) medido por la metodología CEPAL aplicada por la Dirección General de Estadística y Censos (D.G.E.y C.). A medida que se deteriora el medio ambiente (indicadores de carencias críticas) se incrementa en forma exponencial el porcentaje de niños con Retraso de Talla (R.T.). Los resultados muestran un país que no alcanza los niveles nutricionales de un país desarrollado (población de referencia) sin llegar al deterioro de algunos países de América Latina. En su conjunto existe un 80.3 por ciento de niños con una talla normal (superior a -1DS) cuando se debería esperar un 84.1 por ciento. El 4.0 por ciento de los niños presentan una talla inferior a -2DS, cuando en una población bien nutrida se esperaría un 2.3 por ciento. Montevideo presenta una mejor situación nutricional que el total del país. El interior rural, presenta mejor situación que el urbano, y las localidades pequeñas de menos de 5.000 habitantes son las más afectadas. Las niñas han mostrado una situación nutricional ligeramente superior a los varones. Dada la extensa red de escuela distribuídas en todo el país es factible desarrollar una metodología en forma periódica y a bajo costo como forma de monitoreo y vigilancia de la situación nutricional. Los resultados alcanzados estimulan a desarrollar un afinado de la metodología logrando minimizar los errores en la medición de la talla por parte de los maestros. Ello posibilitará la disponibilidad de información periódica y sistemática que permita identificar poblaciones objetivo que requieran de políticas específicas para la solución de sus problemas y por otra parte que permita seguir la evolución en sucesivos Censos Nacionales de Talla