TEDE Coleção:
http://www.bdtd.uerj.br/handle/1/3554
2024-03-28T21:17:19ZEfeitos sexo-dependentes do modelo de esquizofrenia pela exposição neonatal de camundongos à fenciclidina
http://www.bdtd.uerj.br/handle/1/20995
Título: Efeitos sexo-dependentes do modelo de esquizofrenia pela exposição neonatal de camundongos à fenciclidina
Autor: Souza, Thainá Pereira de
Primeiro orientador: Villaça, Yael de Abreu
Abstract: Schizophrenia affects 0.9% of the world population. It is considered a neurodevelopmental disorder, although its full manifestation and diagnosis occur often between late adolescence and early adulthood. After its establishment, three types of symptoms are observed: positive, negative, and cognitive. There are marked sexual differences in schizophrenia, with a higher and earlier incidence in men, who also have more severe negative and cognitive symptoms and a worse response to antipsychotics. Despite these differences, no established animal models mimic them, making it difficult to understand the sex-dependent pathophysiologic mechanisms of schizophrenia and to develop more efficient treatments. Thus, in this study, we used a developmental model of schizophrenia by the neonatal administration of phencyclidine (nPCP), an NMDA receptor antagonist, to investigate whether it induces behavioral and neurochemical changes in a sex-dependent manner. We also evaluated the impact of olanzapine, an atypical antipsychotic, on these changes. C57BL/6 mice of both sexes received subcutaneous injections of phencyclidine at doses of 5, 10, or 20mg/kg (nPCP5, nPCP10, nPCP20), or saline, at postnatal days (PN) 7, 9, and 11. A Naïve group was used to assess the impact of stress associated with injections. At PN30, early adolescence, we quantified by Western Blotting, the NR1 subunit of the NMDA receptor and the postsynaptic protein PSD-95 in the frontal cortex and hippocampus. From PN48 to PN50, the animals were submitted to the following behavioral tests: open field (OF), to check for locomotor hyperactivity associated with positive symptoms; social interaction (SI) to measure a change associated with a negative symptom; and prepulse inhibition (PPI) to assess sensorimotor gate integrity. Olanzapine was administered 30min before each test. There were no differences between Naive and Salina animals, which were pooled in subsequent analyses. In the OF, both nPCP males and females were hypoactive, but males were more sensitive, expressing hypoactivity even at the lowest dose of nPCP. In the SI, impairments in social interaction were identified only in males; in nPCP5 and nPCP20 animals. In the PPI, nPCP males and females showed deficits, with signs of greater severity in males, as they showed a reduction in the percentage of inhibition by the pre-pulse of lower intensity. Olanzapine failed to reverse the behavioral changes caused by nPCP and, in some situations, its administration intensified the effects of the neonatal model. Olanzapine caused more severe hypolocomotion in nPCP males and, particularly in the SI, nPCP10 males only showed deficits if exposed to this antipsychotic. Consistent with the data obtained in the behavioral assessments, we identified a decrease in NR1 protein expression in the frontal cortex only in males. These results suggest that nPCP can be used to model sex-dependent differences identified in patients with schizophrenia. The ineffectiveness and the behavioral damage associated with the protocol adopted for the administration of olanzapine also suggest the need for further studies with the aim of investigating the efficacy and safety of this drug during adolescence
Instituição: Universidade do Estado do Rio de Janeiro
Tipo do documento: Dissertação2022-09-27T00:00:00ZO óleo de capivara livre e em nanoemulsão induz efeitos benéficos na morfofisiologia hepática em camundongos C57BL/6 obesos
http://www.bdtd.uerj.br/handle/1/20947
Título: O óleo de capivara livre e em nanoemulsão induz efeitos benéficos na morfofisiologia hepática em camundongos C57BL/6 obesos
Autor: Alves, Luciana Lontro
Primeiro orientador: Carvalho, Jorge José de
Abstract: Obesity is a complex chronic disease characterized by excess body fat (adiposity) harmful to health; it has been characterized as a major global health problem. Can be associated with several diseases such as non-alcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFAs) are lipid mediators that have anti-inflammatory characteristics and can be found in animals and vegetables, with capybara oil being a promising source. However, they are easily oxidized when in contact with oxygen, and the way to avoid this oxidation and, consequently, increase the bioavailability of PUFAs is pharmaceutical nanotechnology. Thus, the aim of the study is to evaluate the effects of two pharmaceutical presentations of capybara oil (free and in nanoemulsion) on the hepatic alterations established by obesity in C57Bl/6 mice. Sixty C57Bl/6 male mice at 3 months of age were used and received a control or high-fat diet for 18 weeks. From the 15th to the 18th week, the animals received treatment - via orogastric gavage - with placebo, or free capybara oil (5000 mg/kg/day) (OCL), or capybara oil nanoemulsion (100 mg/kg/day) (OCN), or lower concentration of free capybara oil (100 mg/kg/day) (OC100) or white nanoemulsion (NB). Parameters related to body mass, glucose tolerance, blood pressure, evaluation of the lipid profile and liver enzymes, percentage of hepatic steatosis, the process of cell death with the apoptotic pathway and ultrastructure of hepatocytes were analyzed. The high-fat diet generated biochemical damage in mice and changes in the structure and ultrastructure of the liver of these animals. The two pharmaceutical formulations of capybara oil were able to restore the changes caused by obesity. Thus, we conclude that both OCL and OCN have beneficial effects on serum biochemistry, histopathology of the liver of obese mice, improving hepatic steatosis and decreasing the activation of the apoptotic pathway, in addition to being able to restore the ultrastructure of hepatocytes. These findings are relevant for the development of new translational therapies in humans for the treatment of obesity and NAFLD
Instituição: Universidade do Estado do Rio de Janeiro
Tipo do documento: Dissertação2022-08-29T00:00:00ZComparação entre o uso do óleo de oliva e ácidos graxos em lesões cutânes agudas em camundongos
http://www.bdtd.uerj.br/handle/1/20652
Título: Comparação entre o uso do óleo de oliva e ácidos graxos em lesões cutânes agudas em camundongos
Autor: Martins, Rayssa Lopes
Primeiro orientador: Costa, Andréa Monte Alto
Abstract: Skin lesions can be a serious health problem due to the associated morbidity and high costs involved in their treatment. A commercial formulation rich in essential fatty acids and triglycerides is widely used to prevent and treat injuries, however, this formulation has a high cost, making access to this treatment difficult. However, it has already been shown that, in some situations, olive oil, which has a low cost, can promote skin repair by having antioxidant and anti-inflammatory properties. The hypothesis arises that olive oil is a product capable of assisting tissue repair, similar to a formulation rich in fatty acids. The aim of the study was to compare the effects of a commercial formulation rich in fatty acids with olive oil on the healing of acute lesions in mice. Male Swiss mice were randomly divided into 3 groups: control, olive oil and fatty acids, treated respectively with mineral oil, extra virgin olive oil and fatty acid solution. The lesions were performed on the mice's back and treated topically with the compounds. Six days after the injury, injuries treated with olive oil and fatty acids decreased compared to the control group. Olive oil decreased the amount of neutrophils. VEGF expression was increased in the olive oil and fatty acid groups. In addition, olive oil proved to be an antioxidant because it has a lower amount of ROS, nitrite and TBARS compared to the control group. With the results obtained it was possible to conclude that both the topical application of olive oil and a compound rich in fatty acids was able to improve the healing of acute lesions in mice
Instituição: Universidade do Estado do Rio de Janeiro
Tipo do documento: Dissertação2020-12-14T00:00:00ZReatividade da astroglia durante o desenvolvimento da retina de ratos submetidos a um modelo de hipóxia-isquemia pré-natal
http://www.bdtd.uerj.br/handle/1/20312
Título: Reatividade da astroglia durante o desenvolvimento da retina de ratos submetidos a um modelo de hipóxia-isquemia pré-natal
Autor: Fonseca, Lara Silva
Primeiro orientador: Krahe, Thomas Eichenberg
Abstract: The hypoxic-ischemic insult (HI) is responsible for several CNS compromises during its development or at adulthood. Its consequences can cause varying degrees of retinopathy and visual impairment. Thus, investigating the effects of this insult on the retina may help to elucidate the mechanisms responsible for the consequences and thus outline therapeutical approaches. This work sought to mimic the most common human event, which occurs prenatally and may be irreversible. Using a model in which the uterine and ovarian flow of the pregnant rat is obstructed for 45 minutes on the 18th gestational day, a decrease in the optic nerve thickness and in the retinal projections in the dorsal lateral geniculate nucleus (NGLd), GCL loss and failure to maintain pupillary constriction have been reported. The aim of this study was to evaluate the retinal glial reactivity of Wistar rats during development (at two, nine, twenty three and thirteen postnatal days). The surgery for HI induction was performed with obstruction of uterine and ovarian flow (HI group) for 45 minutes on the eighteenth day of gestation. Animals that underwent all surgical procedure except for obstruction of blood flow constitute the sham-operated group (SH). Histological evaluation was performed to evaluate the development and response to the HI insult in cells of the retinal astroglial lineage, astrocytes and Muller's glia, using immunohistochemistry for glial fibrillary acidic protein (GFAP) and vimentin (VIM). Immunostaining for the GLAST glutamate transporter was also evaluated. The results showed that HI insult promotes an increase in GFAP and VIM labeling on the thirtieth postnatal day, as well as alters the immunostaining pattern for the GLAST transporter by anticipating the peak of labeling to the ninth day in the HI group. Taken together, the results show that, also in the retina, a gliosis occurs, as also described in other brain regions in rats submitted to this prenatal HI model. In addition to the results obtained for the GLAST transporter, we reinforce the hypothesis that glutamate transport alterations may contribute to glutamatergic excitotoxicity, one of the events responsible for neuronal death in this kind of lesion. Once more, we showed that the prenatal HI model used in this study is an important tool to be used in order to understand the mechanisms of the lesions caused by HI during development, as well as for the evaluation of possible therapeutic strategies.
Instituição: Universidade do Estado do Rio de Janeiro
Tipo do documento: Dissertação2019-08-30T00:00:00Z