Banca de QUALIFICAÇÃO: MARIA CAMILA ACERO CASTILLO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : MARIA CAMILA ACERO CASTILLO
DATE: 28/04/2025
TIME: 14:00
LOCAL: Sala de seminários departamento de Ciências Fisilógicas (CFS)
TITLE:

“Evaluation of the antiepileptic effect of the neuropeptide Neurovespina in a DREADDsinduced epilepsy model in rodents”

KEY WORDS:

“Epilepsy; Área Tempestas; DREADDs; Neurovespina"

PAGES: 100
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

“One of the most prevalent subtypes of epilepsy is temporal lobe epilepsy (TLE), which has clinical relevance due to its severity and the high percentage of adult patients who are resistant to available antiepileptic drugs. In searching for technically more refined and ethically appropriate animal models, the DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) technique, also known as chemogenetics, has opened new frontiers in the study of drugs with potential clinical applications. Therefore, the objective of this study is to evaluate the antiepileptic effect of the peptide Neurovespina in a DREADDs-induced epilepsy model in rodents. To achieve this, a DREADDs-induced epilepsy animal model was developed in two phases. In the first phase, nine animals were divided into three groups (n=3 per group). Subjects in each group were intracerebrally infused with a viral vector for the expression of chemogenetic receptors in the area tempestas (AT), specifically: pAAV-hDlx-GiDREADD-dTomato-Fishell-5; pAAV-GFAP-HArM3D(Gs)-IRES-mCitrine; and pAAV-CaMKIIa-hM3D(Gq)-mCherry. After surgical recovery, the animals received twice-weekly administrations (1 and 5 mg/kg) of ClozapineN-oxide (CNO) for four weeks to induce acute epileptic seizures. It was observed that only animals expressing the GiDREADD receptor developed epileptic seizures after CNO administration. In the second phase, eight animals were intracerebrally infused with the pAAV-hDlx-GiDREADD-dTomato-Fishell-5 vector to promote GiDREADD receptor expression in the area tempestas (piriform cortex). The animals underwent two behavioral tests with randomized CNO doses (5 or 10 mg/kg). GiDREADD receptor activation induced epileptic seizures in a dose-dependent manner, successfully triggering Status Epilepticus (SE) in most animals. The latency to SE was similar for both CNO doses. Following the development and validation of the animal model, an additional experimental phase was conducted with repeated administration of Neurovespina to evaluate its antiepileptic effect. The data from this stage are currently being analyzed. As far as the literature review allowed, this study represents one of the first reports of epileptic seizure induction via the DREADDs technology, contributing to advances in epilepsy research and epileptogenesis.”

COMMITTEE MEMBERS:
Externa ao Programa - 2937927 - DJANE BRAZ DUARTE - nullExterna ao Programa - 1302038 - LUANA CRISTINA CAMARGO - nullInterna - 2567703 - MARCIA RENATA MORTARI
Presidente - 1952915 - RAFAEL PLAKOUDI SOUTO MAIOR