During the development of the central nervous system (CNS) there is a great possibility of permanent effects in consequence of environmental disturbances. Nutritional deficiency is one of the factors that impair the normal CNS formation. In general, the protein deficiency evokes, beyond the damages in the maturation of nervous system, several consequences in body growth, biochemical maturation, motor function and the major cognitive functions. These effects were observed in undernourished children all over the world. Even in a restricted period, the malnutrition status may evoke permanent impairments in feeding behavior and in metabolism. Rats submitted to malnutrition during development, showed a marked decrease in the number of myelinated fibers. This condition may reflect a failure in the beginning of the wrapping of axons by oligodendroglial processes and/or a delay in the myelin synthesis. Myelin basic protein (MBP) is an intracellular oligodendrocyte protein that is directly related to the formation of the myelin sheath. In this study we verified the temporal pattern of MBP expression, by immunohistochemical and immunoblotting analyses, in a model of protein malnutrition induced during the first half of the lactation period. We showed that MBP expression was impaired in our malnutrition model and that some of the effects were maintained in adulthood, with possible consequences in the maturation of myelin sheath.
A previous study using the 2'3'cyclic nucleotide 3'phosphodiesterase (CNPase), an oligodendroglial marker that also stain ensheathed fibers, showed a decrease in the number of immunoreactive fibers and a change in the pattern of CNPase immunoreactivity (CNPase+) in hypothyroid animals. CNPase+ fibers, in mature hypothyroid animals, showed a continuous pattern of staining in contrast with a discontinuous one in controls. As CNPase, in adult animals, can be found only in regions in which oligodendrocyte cytoplasm remains as internal, external and paranodal loops, it was suggested that the reduction of thyroid hormone levels leads to a failure in myelin compaction. Previous data showed a higher frequency of some abnormalities in myelin sheath as multiple cytoplasmic loops and redundant myelin profiles in mutant animals that present a failure in myelin compaction. The increase in the frequency of these abnormalities (multiple internal and external loops and redundant myelin) indicates a failure in the interrelations between the axons and the oligodendroglial processes. To verify if the thyroid hormone deficiency during CNS development disturbs these interrelations, we evaluated the frequency of the morphological abnormalities (multiple internal and external loops and redundant myelin) in myelin sheath of corpus callosum (cc) in experimental hypothyroidism. Randomic fields were kept by electron microscopy and the analysis of the frequency of morphological abnormalities showed a significant difference in hypothyroid animals at 60-day-old (PND60), with no significant differences at 90-day-old (PND90) animals. The frequency of multiple internal loops is higher in hypothyroid animals at PND60 that indicates a disturbance in the wrapping by the oligodendroglial process. These findings showed that thyroid hormone might modulate the axon-oligodendroglial relationships that are important for the adequate temporal sequence of events that occur during myelinogenesis, with possible consequences on myelin compaction.
The effects of hypothyroidism on oligodendroglial differentiation and myelination are for the first time studied by immunohistochemical localization of an early oligodendroglial marker, the 2'3'cyclic nucleotide 3'phosphodiesterase (E.C. 3.1.4.37-CNPase), in developing rats. Two groups received methimazol; one during gestation (H) and another postnatally (PN). One H sub-group received thyroxine after birth (T). We observed a delay in CNPase expression followed by a decrease in the number of CNPase immunoreactive fibers in both H and PN groups. The T sub-group was not different from controls. Furthermore, the immunoreactive fibers, in mature hypothyroid animals, showed a continuous pattern of staining in contrast with a discontinuous one in controls. Myelinogenesis is a highly regulated timed event. CNPase links myelin related proteins to the cytoskeleton also interacting with membrane lipids during extension and wrapping of the oligodendroglial process around the axon (ensheathment phase). In mature myelinated fiber the CNPase is absent from compact myelin sheath, being located only in the inner and outer loops and in paranodal loops. Thus, our data suggest a disorder in myelin compaction and point once more to the post-natal period as critical for the mechanisms that are thyroid hormone regulated in myelinogenesis.
Thyroid hormone (T3) deficiency impairs the development of the CNS, particularly myelination. We have previously described an increase in the frequency of morphological abnormalities in the central myelin sheath in a hypothyroidism model, which reinforced the hypothesis of a role for T3 in myelin compaction. However, there are no data concerning the cellular distribution of myelin proteins in hypothyroid animals. In the present work, we describe the distribution of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin basic protein (MBP) and proteolipid protein (PLP) throughout the central myelin sheath of a hypothyroidism model. We used euthyroid and hypothyroid adult rats at 90 days of age. In order to induce hypothyroid status, animals received 0.02% methimazol from the 19th gestation day onwards. After perfusion with a fixative mixture, small pieces of corpus callosum were obtained, dehydrated and embedded in LR White resin. Ultrathin sections were immunoreacted, using specific antibodies revealed by a secondary antibody coupled to colloidal gold particles of 10nm. Gold particle density per region of myelin sheath for each one of these proteins was obtained. In normal animals, CNPase, PLP and MBP were identified in sites that had already been described in previous studies. In hypothyroid animals, CNPase was identified in the region corresponding to compact lamellae, which normally does not contain this protein, while, in this same region, PLP and MBP immunolabeling were decreased. These results suggest that thyroid hormone deficiency impairs the distribution of the major oligodendrocyte/myelin markers. This effect may justify the reduction in myelin sheath compaction previously demonstrated in a similar model of hypothyroidism.
In Brazil, about 49% of the population does not have access to the sewage collection network, with the consequent direct discharge of their sewage network into water bodies. Due to this scenario, it is essential to investigate the quality of the water consumed by thousands of people along the Negro and Resende Rivers. The present study analysis the waters of the Negro and Resende rivers, located in Dois Rios River Basin, in the municipality of Duas Barras, Rio de Janeiro State (RJ, SE Brazil), based on the Water Quality Index proposed by the National Sanitation Foundation (United States). The population of the district located in the municipality of Duas Barras dumps the domestic sewage directly into the hydrographic network. The analyzed parameters were: turbidity, total solid residue, total phosphorus, total nitrogen, biochemical oxygen demand (BOD), hydrogenation potential, temperature, dissolved oxygen and thermotolerant coliforms. The values obtained from the calculation of the Water Quality Index (WQI) showed a variation from 40 to 68, meaning that the quality of water vary between bad and acceptable in the study area. The samples collected in the urban area contained values for thermotolerant coliforms in disagreement with the maximum value permissible for classes 2 and 3 of fresh water by CONAMA (Conselho Nacional do Meio Ambiente; a Brazilian Council for the Environment) Resolution 357/2005. The results of the analyzes confirmed the contamination of the two rivers by the discharge of domestic effluents, showing that actions are necessary to eliminate or minimize the discharge of sewage in the surveyed water bodies, since it may cause public health risks. ResumoNo Brasil, cerca de 49% da população não possui acesso à rede de coleta de esgoto, com o consequente despejo direto da sua rede de esgotos em corpos hídricos. Diante deste cenário, torna-se indispensável investigar a qualidade da água consumida por milhares de pessoas ao longo dos rios Negro e Resende. A presente pesquisa analisou qualitativamente as águas dos rios Negro e Resende, localizados na Bacia Hidrográfica do Rio Dois Rios, no município de Duas Barras/RJ, a partir do índice de qualidade das águas proposto pela National Sanitation Foundation. A população do distrito sede do município de Duas Barras despeja o esgoto doméstico diretamente na referida rede hidrográfica. Os parâmetros analisados foram: turbidez, resíduo sólido total, fósforo total, nitrogênio total, demanda bioquímica de oxigênio, potencial hidrogêniônico, temperatura, oxigênio dissolvido e coliformes termotolerantes. Os valores obtidos no cálculo do índice de qualidade das águas (IQA) mostraram uma variação de 40 a 68, significando uma qualidade da água entre ruim e razoável. As amostras coletadas na área urbana apresentaram valores para coliformes termotolerantes em desacordo com o valor máximo permitido para classes 2 e 3 de água doce, regulamentados pela Resolução CONAMA 357/2005. O resultado das análises confirmou a contaminação dos dois rios pelo lançamento de efluentes domésticos, os quais poderão originar riscos de saúde pública. Os resultado evidenciam a necessidade de se desenvolverem ações para eliminar ou minimizar os despejos de esgotos nos referidos corpos hídricos.
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