Unraveling the molecular and genetic mechanisms of epilepsy

Abstract

This project attempts to enhance the cooperation of two laboratories that work with two models of experimental epilepsy (audiogenic seizures), strengthening collaboration between researchers, encouraging visiting researchers to share knowledge, resources and techniques in which each laboratory has more expertise. All this leads to coordinate a research project that helps to determine the molecular and genetic mechanisms underlying epilepsy. The analysis of the common mechanisms involved in triggering the seizures can provide information on the etiology of epilepsy and help to find possible new targets for antiepileptic treatment. Both audiogenic strains, Genetic Audiogenic Seizures Hamsters from Salamanca, GASH/Sal and Wistar Audiogenic Rat (WAR), constitute an excellent strategy for the study of new pharmacological treatments as the seizures are triggered by an auditory stimulus, which does not present interference when evaluating anticonvulsant drugs. In that context, the two groups are currently involved in the study of the anticonvulsant properties of some molecules derived from Cannabis, and both Principal Investigator are Guest-Editors of a Research Special Topic in Frontiers in Behavioral Neurosciences, entitled "Challenges and conundrums in cannabinoid-based treatments for epilepsy syndromes and associated neurobehavioral comorbidities". The Neurophysiology and Experimental Neuroethology Laboratory (LNNE) at the FMRP-USP is currently developing studies also on Cannabis derivatives, Epilepsy and Neuropsyquiatric Comorbidities (INCT CNPq 465458/2014-9/FAPESP 2014/50891-1; FAPESP Individual Solicitation Process 2019-05957-8; under evaluation). Therefore, the missions and international exchanges of the current SPRINT-FAPESP-USAL Project will be fundamental for the consolidation of integrated, multi-institutional research approaches to this important and contemporary field. Because the two laboratories have a large number of pre- and postdoctoral researchers involved in different research sub-projects, we plan to make a Workshop in Salamanca in September 2020, in which the main lines of research, the most used techniques and standardization of work methodologies will be presented by the two research teams, and as result, maximize the development of a collaborative project through brainstorming sessions. In order to make the Workshop the researchers from Ribeirão Preto will travel to Salamanca to expose their current research projects which includes sessions on different behavioral (neuroethology, graph construction, etc.), image (light and fluorescent microscopy) and molecular biology (design of primers, analysis of gene expression, etc.), methodologies and analyses. Additionally, the Laboratory of Audiomotor Disorders at Salamanca has a large experience in quantification using image analysis of brain tissue sections, and thereby one Graduate Student/Research Technician from Ribeirão Preto will perform a research stay during one month to analyse the inner ear morphology of the WAR. The results will allow a comparative study between the two animal models of epilepsy. Finally, Dr. Muñoz, the head of the animal facilities of the University of Salamanca, will visit his counterpart in Ribeirão Preto to develop improvements in the housing, handling, care, and maintenance of the seizure-prone colony. (AU)