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Study of the alterations in the development, behavior and cerebral biochemistry of male rats exposed to the environmental atmospheric pollution in the intra-uterine phase

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Ana Claudia Tedesco Zanchi
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Angela Cristina do Valle; Paulo Afonso de André; João Vicente de Assunção; Mariangela Macchione; Mitiko Saiki
Advisor: Angela Cristina do Valle

Experimental studies done at our laboratory demonstrated that the inhalation of residual oil fly ash by the adult rats decreased motor activity of the animals in the open-field test. Additionaly, we showed that rats which inhalated residual oil fly ash preserved its habituation capacity. In this study, oxidative stress in striatum and cerebellum might be the cause of motor activity alterations. However, there were any studies about air pollution and behavioral alterations in Porto Alegre. Based on our previous works and in the literature, our objective was to investigate if the exposure to air pollution during intrauterine and lactation periods would damage the short term discriminative and spatial memories and if the mechanisms would be dependent of oxidants. For such, female pregnant rats were exposed to the filtered air and to the non filtered air during the 21 days of gestation. At the end of the breast-feeding period, the males were separate and divided in 4 experimental groups (n =24): 1) Filtered (F): - pre and post-natal exposure until adulthood in filtered air; 2) non filtered/filtered air (NFF): pre-natal period in non-filtered air until PND21 and post-natal in filtered air until adulthood; 3) filtered air/non-filtered air (FNF): pre-natal period in filtered air until PND 21 and post-natal period in non-filtered air until adulthood; 4) non filtered air (NF): pre and post-natal periods in non-filtered air.The animals were exposed the pollution for 150 days. The animals were divided in 3 lots: lot 1: n=6 animals per group; after anesthesia, the animals were perfused with saline solution following by paraformaldehyde 4%, the brain was removed and dissected in cortex, hippocampus and striatum for histological analyses by stereological techniques; lot 2: n=12 rats per group; submitted to behavioral tests; one day after the tests, those animals were euthanized by decapitation, the brain was removed and dissected in the same way mentioned previously for oxidative stress analysis; lot 3: 6 animals per group; the animals were decapitated and the troncular blood was collected to analyze the toxic and the essential trace elements. The cortex presented lipoperoxidation in NF group when compared to other groups, as well as a high concentration of Cd in the blood. The group NFF presented higher blood concentration of Cu, Se and Zn when compared to other groups. There was a decrease in the discriminative capacity in the group NF when compared to other groups. In the hippocampus and striatum, increases of lipidperoxidation were observed in the groups FNF and NF, respectively, when compared to other groups. Spatial memory of all groups was preserved. We observed the each brain structure reacts in a different way to oxidative stress. The NF cortex group presented an increased of lipidperoxidation. In this group, there was higher Cd blood concentration, which passes through placenta and it is fetotoxic. It might be possible that Cd dislocated Zn of the active site of CuZn superóxido dismutase resulting in inactive forms of this enzyme. The Cd also depletes reduced glutathione. Moreover, Cd may dislocate the Fe and Cu from its storage proteins to react with oxygen peroxide increasing the hydroxyl radical production by Fenton reaction. The group NF presented a decrease in the capacity to discriminate two different objects. Cd may act in an indirect way reducing the antioxidant capacity of CuZn superxidodismutase and of the glutathione and increasing the hydroxyl radical production. Lipoperoxidation in NF cortex caused by the Cd may be one of the mechanisms which explain the loss of discriminative capacity. However, the group NFF, whose air pollution exposure was in the pre-natal period, did not present increase of lipidperoxidation. The higher concentrations of essential trace elements (Cu, Se and Zn) may protect this group against oxidative stress. These elements are cofactor of antioxidants enzymes, superoxidodismutase and glutathione peroxidase and increased its activities during the intra-uterine exposure to air pollution. The group FNF presented lipidperoxidation increase in the hippocampus, but there was no difference in the spatial memory tested with Morris\' maze. Therefore, considering our data, we suggested that the increase of lipidperoxidation caused indirectly by Cd, which was adsorbed in particulate matter surface, may be one of the mechanisms which explain the loss of short-term discriminative memory (AU)