Hypoactivity of the central dopaminergic system and autistic-like behavior induced by a single early prenatal exposure to lipopolysaccharide

The aim of the present study was to evaluate the behavioral patterns associated with autism and the prevalence of these behaviors in males and females, to verify whether our model of lipopolysaccharide (LPS) administration represents an experimental model of autism. For this, we prenatally exposed Wistar rats to LPS (100 mu g/kg, intraperitoneally, on gestational day 9.5), which mimics infection by gram-negative bacteria. Furthermore, because the exact mechanisms by which autism develops are still unknown, we investigated the neurological mechanisms that might underlie the behavioral alterations that were observed. Because we previously had demonstrated that prenatal LPS decreases striatal dopamine (DA) and metabolite levels, the striatal dopaminergic system (tyrosine hydroxylase [TH] and DA receptors D1a and D2) and glial cells (astrocytes and microglia) were analyzed by using immunohistochemistry, immunoblotting, and real-time PCR. Our results show that prenatal LPS exposure impaired communication (ultrasonic vocalizations) in male pups and learning and memory (T-maze spontaneous alternation) in male adults, as well as inducing repetitive/restricted behavior, but did not change social interactions in either infancy (play behavior) or adulthood in females. Moreover, although the expression of DA receptors was unchanged, the experimental animals exhibited reduced striatal TH levels, indicating that reduced DA synthesis impaired the striatal dopaminergic system. The expression of glial cell markers was not increased, which suggests that prenatal LPS did not induce permanent neuroinflammation in the striatum. Together with our previous finding of social impairments in males, the present findings demonstrate that prenatal LPS induced autism-like effects and also a hypoactivation of the dopaminergic system. (c) 2012 Wiley Periodicals, Inc.

Lipopolysaccharide-Induced Sickness Behaviour Evaluated in Different Models of Anxiety and Innate Fear in Rats

The fact that there is a complex and bidirectional communication between the immune and nervous systems has been well demonstrated. Lipopolysaccharide (LPS), a component of gram-negative bacteria, is widely used to systematically stimulate the immune system and generate profound physiological and behavioural changes, also known as sickness behaviour (e.g. anhedonia, lethargy, loss of appetite, anxiety, sleepiness). Different ethological tools have been used to analyse the behavioural modifications induced by LPS; however, many researchers analysed only individual tests, a single LPS dose or a unique ethological parameter, thus leading to disagreements regarding the data. In the present study, we investigated the effects of different doses of LPS (10, 50, 200 and 500 mu g/kg, i.p.) in young male Wistar rats (weighing 180200 g; 89 weeks old) on the ethological and spatiotemporal parameters of the elevated plus maze, light-dark box, elevated T maze, open-field tests and emission of ultrasound vocalizations. There was a dose-dependent increase in anxiety-like behaviours caused by LPS, forming an inverted U curve peaked at LPS 200 mu g/kg dose. However, these anxiety-like behaviours were detected only by complementary ethological analysis (stretching, grooming, immobility responses and alarm calls), and these reactions seem to be a very sensitive tool in assessing the first signs of sickness behaviour. In summary, the present work clearly showed that there are resting and alertness reactions induced by opposite neuroimmune mechanisms (neuroimmune bias) that could lead to anxiety behaviours, suggesting that misunderstanding data could occur when only few ethological variables or single doses of LPS are analysed. Finally, it is hypothesized that this bias is an evolutionary tool that increases animals security while the body recovers from a systemic infection.

Efeito das condições ambientais no nível de ruído emitido por leitões

Objetivou-se, com este trabalho, avaliar a influência das variáveis ambientais nos níveis de ruídos emitidos por suínos e quantificar as faixas em dB comparativamente às condições de conforto térmico estabelecidas pela literatura. O experimento foi conduzido em câmara climática, onde foram alojados cinco leitões em fase de creche, submetidos à variação na temperatura ambiente de 20°C a 38°C e umidade relativa de 50% a 80%. Decibelímetros foram instalados para o registro dos níveis de ruídos e sensores dataloggers para os dados de temperatura e umidade relativa. O nível de atividade foi utilizado para quantificar a movimentação dos animais por intermédio de análise de imagens. Análises de correlação e regressão foram aplicadas nos dados para análise estatística. As variáveis ambientais influenciam na emissão de ruídos pelos leitões quando expostos a diferentes condições térmicas. Os níveis de ruídos foram estabelecidos em faixas de acordo com a condição térmica a que animais foram submetidos. Para a condição de conforto (20 a 23°C), níveis de ruídos na faixa de 70 a 75dB; condição de alerta (23 a 30°C), níveis de ruídos na faixa de 60 a 70dB e para condição de estresse térmico (acima de 30°C), na faixa de 55 a 60dB.