Epilepsia Open^® Prize 2019 Basic Science

Read the winning article “Facilitation of kindling epileptogenesis by chronic stress may be mediated by intestinal microbiome"

An interview with Jesús-Servando Medel-Matus, 2019 Epilepsia Open Prize winner for Basic Science Research

Who are you?

I’m a postdoctoral fellow in the Developmental Epilepsy Research Laboratories at the David Geffen School of Medicine of the University of California, Los Angeles (UCLA). Previously, I graduated with honors of the Master and PhD programs of the Neuroethology Institute at the University of Veracruz, Mexico.

During my PhD studies I worked on the evaluation of the role of neuroinflammation mediators on the neuronal death induced by status epilepticus in the developing brain. Presently, I am focused in the study of the neurobehavioral comorbidities of the epilepsy.

What got you interested in epilepsy research?

At the begining of my postgraduate training I attended numerous courses, lectures and conferences related to neuroscience. One of the professors, who is an expert in epilepsy research in my country, Dr. Leonor Lopez-Meraz, used to use examples related to epilepsy in her classes. I was impressed by her passion and enthusiasm for epilepsy research. That was the very first time that I became interested in the complexity of epilepsy. Subsequently, Dr. Lopez-Meraz accepted to be my PhD mentor. More recently, since I have been working at UCLA under the extraordinary mentorship of Dr. Andrey Mazarati and Dr. Raman Sankar, my interests have expanded to the neurobehavioral comorbidities in epilepsy, especially depression and anxiety, and lately the role of dysbiosis in mechanisms of epilepsy and its comorbidities.

Explain for our general readership what question your study addressed and how did you go about designing you study?

There has been increasing interest in the role of gut microbiome in health and disease. The dysregulation of the gut-brain axis implicates intestinal microbiota in several brain disorders such as depression, anxiety, schizophrenia, autism, etc. However, studies of the connection between dysbiosis and epilepsy remains limited. Furthermore, stress (which itself is closely linked to depression) leads to complex changes in the composition of intestinal microbiota which may facilitate epileptogenesis. We used multidirectional microbiome transfer paradigm between stressed and non-stressed animals to examine the contribution of stress-induced dysbiosis on the susceptibility to epilepsy.

To induce dysbiosis, the rats were subjected to chronic restraint stress. The cecal content from stressed and sham-stressed donors was transplanted via oral gavage to recipients,in which commensal microbiota had been depleted by antibiotics. After microbiota transplant, the recipients were subjected to the electrical kindling of the basolateral amygdala, in order to evaluate their susceptibility to epilepsy.

What were the results and how do you interpret your findings?

We found that transplant of intestinal microbiota from chronically stressed to naive rats accelerated kindling and increased the duration of kindled seizures. On the other hand, the transplant of microbiota from naive to stressed animals counteracted the
proepileptic effects of stress. Our findings suggest that the perturbations in the gut microbiome associated with chronic stress, may contribute to the increased susceptibility to epilepsy.

What next steps in epilepsy research are you taking and what are your career goals?

The subsequent phases of this investigation are to perform microbiome sequencing in both donors and recipients to confirm accurately microbiome changes after stress and microbiome transplants. We will also investigate the consequences of the stress-induced dysbiosis predisposing to epilepsy which may include the examination of inflammatory processes, dysregulation of vagal afferents, epilepsy-relevant bioactive peptides, as well as metabolomic analysis.

My main professional goal is getting the necessary experience to lead my own research group related to epilepsy.Moreover, I would like to educate people in science, particularly I would like to encourage the study of science in children of Latin and/or  Mexican-American families who historically are poorly interested in this discipline. I am convinced that the affinity for science begins at a young age and the guidance provided by a member of the same minority will promote the enthusiasm to start a scientific career.

For that reason, at the same time of the development of my research, I am planning to collaborate with non-profit organizations to support Mexican migrants, and their families in terms of education, and promotion of cultural activities. Also, I am interested in developing studies focused on the impact of the support provided by this type of organization on the quality of life of the migrants and their mental wellness.

What does the Epilepsia Open Prize mean for you, your laboratory, research institute, and your future?

I am very honored to receive the 2019 Epilepsia Open Basic Science Research Prize. I wish to thank Epilepsia Open Editors and Editorial Board for such high recognition of my work. Throughout my professional life I have worked hard to be a good scientist. I feel very gratified that my passion for the study of epilepsy has been recognized by this important journal.

However, I must admit that this research has not been developed only by me. This is a team effort led by Dr. Andrey Mazarati and Dr. Raman Sankar, and carried out with the valuable collaboration of my colleague Don Shin. I am convinced that all members of our laboratory deserve this award, which encourages us to continue contributing to the study of epilepsy in order to improve the quality of life of people who suffer of this condition.

I feel extremely privileged to collaborate with the UCLA neuroscience community because I have had the opportunity of being in touch with respected neuroscientists whose example inspired me to win this prize.

I am looking forward to sharing our findings and discussing the most recent advances in the study of epilepsy with other neuroscientists at the 33rd International Epilepsy Congress that will take place in Bangkok, Thailand.

Finally, I consider that this award signifies a great incentive for my career, mainly because I am belonging to an underrepresented group in science. Therefore, I would like to be an example to follow for other Mexican and Latin American people to pursue science careers.

Aristea Galanopoulou and Dong Zhou
Editors-in-Chief, Epilepsia Open