Dissertação
Alterações sexo-específicas na memória e homeostase glutamatérgica induzidas por bisfenol A em camundongos: efeito do disseleneto de difenila
Fecha
2017-03-03Autor
Jardim, Natália da Silva
Institución
Resumen
Bisphenol A (BFA) is an endocrine disruptor with high toxicological potential, used in the manufacture of
synthetic polymers, including food and beverage packaging. Even though the deleterious effects of BPA
exposure have been well reported, mainly in the early stages of life, none possible therapeutic intervention was
developed. In this sense, diphenyl diselenide, (PhSe)2, one of the most studied organic selenium compounds, is a
pleiotropic molecule with great therapeutic potential at pharmacological doses. The scientific literature shows
different pharmacological properties; among them, the protective effects on the cognitive impairment induced in
different experimental models were already described. Taking it into account, the objective of the present
dissertation was to investigate the effects of (PhSe)2 on the memory impairments induced by BPA exposure to
male and female mice and the possible involvement of glutamatergic system in these effects. Three-week-old
male and female Swiss mice received BPA (5 mg/kg), intragastrically, from 21st to 60th postnatal day. After, the
animals were intragastrically treated with (PhSe)2 (1 mg/kg) during seven days. The mice performed the
behavioral memory tests, Morris water maze, object recognition and step-down passive avoidance. The [3H]
glutamate uptake and NMDA receptor subunits (2A and 2B) analyses were carried out in the hippocampus and
cerebral cortex of mice. The results demonstrated that the BPA exposure induced impairment of object
recognition memory in both sexes. However, it caused impairments in spatial memory in female and in the
passive avoidance memory in male mice. Besides, BPA caused a decrease in the [3H] glutamate uptake and
NMDA receptor subunits in the cortical and hippocampal regions depending on the sex. The effects of treatment
with (PhSe)2 on reversing the alterations in the different types of memory caused by exposure to BFA were
independent of sex. As well as the restorative effects of this compound in the [3H] glutamate uptake and NMDA
receptor subunits levels in the hippocampus and cortex of mice. In conclusion, the results of this study showed
that subchronic exposure to BFA during the brain development period induced damage in the memory formation
in a sex-dependent manner and these effects may be related to alterations in the glutamatergic homeostasis.
However, (PhSe)2 reversed all behavioral and molecular changes in a sex-independent manner, demonstrating to
be a potential candidate for the treatment of memory damage caused by exposure to BPA in mice.