Banca de DEFESA: ANA LUIZA CAMPOS VILA REAL
Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.STUDENT : ANA LUIZA CAMPOS VILA REAL
DATE: 28/02/2023
TIME: 14:00
LOCAL: meet.google.com/dxc-wnkk-qjj
TITLE:
KEY WORDS:
autism spectrum disorder; valproic acid; animal models; prenatal exposure; development; behavior
PAGES: 67
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUMMARY:
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that includes, approximately, 1% of the world’s population. ASD is characterized by clinical observations of deficits in social communication and interaction and, also, the prevalence of repetitive behaviors and restricted interests. There are many etiologies associated with this disorder, representing the wide phenotypic diversity of ASD. Thus, there are various animal models for the scientific investigation of the mechanisms in which different risk factors (genetic and environmental) cause the development of ASD and for the search of therapeutic interventions. Valproic Acid (VPA) is a pharmaceutical compound used for the treatment of epilepsy, mood disorders and migraines, and its use during gestation has been linked with an increased probability of ASD development in the offspring. There are well established animal models of ASD induced by VPA exposure, although the exact mechanisms by which VPA induces the changes seen in neurodevelopmental trajectory, ultimately leading to the behavioral features found in these models, are unknown. The phenotypes (or endophenotypes) seen in these models expresses differently, depending on which dose of VPA is used, which administration route and which phase of development occurs the exposure to the drug. Therefore, in this study, we aimed to investigate the effects of VPA through intrauterine exposure (VPAiu), directly at rat embryos, at the time window of neural tube closure, testing different doses. Our hypotheses were that VPAiu exposure would lead to the generation of endophenotypes observed in VPA models of ASD; that the endophenotype would be homogeneous within litters; and that the phenotypical severity would increase in a dose-dependent manner. To attest this, we performed a medial laparotomy at pregnant dams, at gestational day (GD) 12, to expose the uterine horns, allowing micro injections of VPA on each embryo. After the pups were born, we followed their development, registered the ultrasonic vocalizations (USVs) induced by maternal isolation and, also, submitted the offspring to behavioral tests (open field and social interaction) to verify the presence of the ASD endophenotype. The two doses of VPA used in this study were able to generate teratogenicity in less than 10% of the injected animals. Through the analysis of dam’s weighting, neonates’ weighting and register of eye-opening date, we found no change at global development amongst groups. We found that VPAiu animals vocalized significantly less USVs that age matched controls at postnatal day (P)7. Only one group of VPAiu animals (VPA 1) explored significantly less the open field apparatus’ nose-poke holes at P21, spent less time at the center of the open field apparatus at P30 and presented an increased number of events at the social interaction zone (ZIS; P35) compared to controls. VPAiu animals did not present social interaction deficits. Through the data obtained in the present research, we can conclude that our methodology (injecting VPA through the intrauterine route) generated teratogenic effects and replicated autistic-like behaviors, characteristic of ASD animal models induced by VPA.
COMMITTEE MEMBERS:
Externo à Instituição - ENRRICO BLOISE - UFMG
Externa ao Programa - 1733434 - RENATA FIGUEIREDO ANOMAL - nullPresidente - 1698305 - RODRIGO NEVES ROMCY PEREIRA