Activation of microglia in specific hypothalamic nuclei and the cerebellum of adult rats exposed to neonatal overnutrition

Much attention has been drawn to the possible involvement of hypothalamic inflammation in the pathogenesis of metabolic disorders, especially in response to a high-fat diet. Microglia, the macrophages of the central nervous system, can be activated by proinflammatory signals resulting in the local production of specific interleukins and cytokines, which in turn could exacerbate the pathogenic process. Because obesity itself is considered to be a state of chronic inflammation, we evaluated whether being overweight results in microglial activation in the hypothalamus of rats on a normal diet. Accordingly, we used a model of neonatal overnutrition that entailed adjustment of litter size at birth (small litters: four pups/dam versus normal litters: 12 pups/dam) and resulted in a 15% increase in bodyweight and increased circulating leptin levels at postnatal day 60. Rats that were overnourished during neonatal life had an increased number of activated microglia in specific hypothalamic areas such as the ventromedial hypothalamus, which is an important site for metabolic control. However, this effect was not confined to the hypothalamus because significant microglial activation was also observed in the cerebellar white matter. There was no change in circulating tumour necrosis factor (TNF) α levels or TNFα mRNA levels in either the hypothalamus or cerebellum. Interleukin (IL)6 protein levels were higher in both the hypothalamus and cerebellum, with no change in IL6 mRNA levels. Because circulating IL6 levels were elevated, this rise in central IL6 could be a result of increased uptake. Thus, activation of microglia occurs in adult rats exposed to neonatal overnutrition and a moderate increase in weight gain on a normal diet, possibly representing a secondary response to systemic inflammation. Moreover, this activation could result in local changes in specific hypothalamic nuclei that in turn further deregulate metabolic homeostasi

Role of diffusible and transcription factors in inner ear development, implications in regeneration

Organogenesis involves a dynamic balance of the mechanisms regulating cell division, differentiation and death. The development of the chicken embryo inner ear offers a well-characterised model at the morphological level to study which signals are implicated in the modulation of cellular activation and commitment. The early developmental decisions that control the origin of the inner ear elements are just beginning to be identified by complementary in vivo and in vitro studies. Insulin-like growth factor-I (IGF-I) and nerve growth factor (NGF) are among the best characterised diffusible factors acting during inner ear development. Although the cellular actions of these factors are beginning to be understood, the signalling pathways triggered by them still remain largely unknown. In this context, viral vehicles can be used to deliver genes and then analyse their functional roles during inner ear development. A model is proposed where the actions of IGF-I and NGF contribute to the combinatorial expression of Jun and Fos family members in particular domains of the otic vesicle. Some of these mechanisms may be also implicated in otic regeneration

Tempos de infância, tempos de escola: a ordenação do tempo escolar no ensino público paulista (1892-1933) Childhood times, school times: the ordering of school time in the São Paulo State School System (1892-1933)

O texto analisa a ordenação do tempo nas escolas primárias paulistas no final do século XIX e início do século XX, período em que se institui e se consolida a arquitetura temporal escolar. Compreende, pois, as primeiras prescrições detalhadas sobre o tempo constantes na reforma republicana da instrução pública de 1892, as regulamentações instituídas no decorrer da Primeira República, até o momento de criação do Código de Educação de São Paulo em 1933, quando se inaugura uma nova fase da instrução pública no estado. O texto busca mostrar como o tempo constitui uma ordem que se experimenta e se aprende na escola. Para a realização deste estudo foram utilizadas fontes documentais, especialmente a legislação e textos oficiais da administração do ensino. As análises incidem sobre dois aspectos: a formulação política do tempo escolar e a organização pedagógica e disciplinar do tempo na escola. Em relação ao primeiro aspecto, mostra como a ordenação do tempo pautou-se pela aspiração de uniformização e controle. Nesse sentido, as autoridades do ensino público procuraram regulamentar a obrigatoriedade do ensino, a freqüência, a duração do curso primário e a jornada escolar. Em relação à organização pedagógica e disciplinar do tempo, põe em destaque a ordenação minuciosa do emprego do tempo compreendendo a racionalização curricular - a seleção e distribuição do conhecimento por séries, aulas, lições, e a definição dos horários.<br>This text analyzes the ordering of time in primary state schools of the State of São Paulo at the end of the 19th century and beginning of the 20th century, a period in which the school time architecture is instated and consolidated. The paper thus starts with the first detailed instructions related to time at schools, which are part of the Republican Reform of Public Schooling of 1892. It continues with the regulations elaborated during the First Republic, and progresses up to the creation of the São Paulo State Education Code of 1933, when a new era of state public education begins. This work tries to show that time is an ordering that is experimented and learnt at school. The study is based on documentary sources, especially legislation and official texts from Education Authorities. The analyses focus on two aspects: the political formulation of school time, and the pedagogical and disciplinary organization of time at school. With regard to the first aspect, the work shows how the ordering of time was driven by an aspiration of standardization and control. In that sense, state school authorities attempted to regulate on mandatory schooling, attendance rules, duration of primary education, and daily attendance time. As to the pedagogical and disciplinary aspect, this study stresses the meticulous ordering of school time including the curriculum rationalization - the selection and distribution of knowledge along grades, classes, and lessons, and the definition of timetables