Andrej O. Župančič Memorial Lecture

Aletta Kraneveld

Digesting the gut-immune-brain axis in brain disorders

Saturday, 30 September 2017
Faculty of Medicine, Ljubljana

Professor Andrej O. Župančič

Andrej O Zupančič

Professor Andrej O. Župančič (27. januar 1916 - 3. december 2007) was the founder and the first Head of the Institute of Pathophysiology at the University of Ljubljana Faculty of Medicine, Slovenia. Under his guidance, the institute became a center of internationally renowned neuroscience research in Slovenia. Being a fascinating person, he attracted many young scientists into this field and incited neuroscience research also in other university and clinical institutions. He was the first Honorary member of SiNAPSA, accepting our invitation when the society was very young, giving its mission his wholehearted support.

Professor Župančič passed away in 2007 and the organizers of the SNC'17 together with his former students and friends in Slovenia dedicate this lecture to his memory.

Professor Aletta Kraneveld

Aletta Kraneveld Aletta Kraneveld (1964) studied Pharmacy at the schools of Pharmacy at University of Amsterdam and Utrecht University, the Netherlands. As a junior researcher she worked at the department of Gastrointestinal Pharmacology of Glaxo Group Research in the UK (1990–1992). She obtained her PhD at the department of Pharmacology, Faculty of Pharmacy, Utrecht University (1994) after which she did a research project at the department of Pathology, Harvard Medical School Boston MA, USA. As a post doc she continued her research as immunopharmacologist at the Utrecht University. In 1999 Aletta Kraneveld was appointed as assistant professor and in 2002 as associate professor at the division of Pharmacology of the department of Pharmaceutical Sciences of the Utrecht University. Since June 2016, Aletta Kraneveld has been appointed as full professor Interdisciplinary Translational Pharmacology at the faculties of Science and Veterinary Medicine of the Utrecht University. She has published 95 papers (H-index: 34) and presented over 40 invited lectures. Besides science, she is an active member of several boards of (inter)national scientific organizations (Dutch Society of Pharmacology, EPHAR, IUPHAR, Netherlands Federation of Innovative Drug research).

Her current research interests involve targeting the interaction between innate and adaptive immunity as well as host-microbiota interactions in chronic (inflammatory) diseases with pharmaceutical as well as medical food concepts. As principle investigator Aletta Kraneveld is focusing her research to in depth study the role of the gut-immune-brain-axis in inflammatory bowel disease, allergy, and neurodevelopmental disorders (autism, preterm birth associated neurodevelopmental and immunological disorders) and neurodegenerative disorders (Parkinson’s disease). The research of the Kraneveld-lab will further enhance the knowledge of the interaction of the immune system and neurons in chronic inflammatory conditions in the gut and CNS. Aletta Kraneveld has set up a new research group within UU, where a strong collaboration with several (inter)national research institutes and industries is part of. The program is the start of a (inter)national neuro-immune platform where academia and industry meet for research on the gut-immune-brain axis as target for medicine and medical food concepts. In the last 5 years more than 20 scientific papers and 5 PhD theses have been published.

Digesting the gut-immune-brain axis in brain disorders

Many CNS disorders are associated with gastrointestinal deficits characterized by motility problems, constipation or diarrhea, (low-grade) inflammation, abdominal pain and discomfort. The frequently reported leaky gut, intestinal inflammation and changes in the composition of the microbiome in patients point to the relevance of gut-microbiome-immune-brain axis in neurodevelopmental and neurodegenerative disorders such as autism spectrum disorder and Parkinson’s disease. Based on (pre)clinical data the talk will shed some light on the possible mechanism of the cross-talk between gut and brain in CNS disorders with a focus on immunological mechanisms. The first part of talk will present (pre)clinical data on gut-immune-brain axis in autism spectrum disorders focusing on the role of the microbiome, immune system (food allergy) and mechanistic target of rapamycin (mTOR). In the second part the relevance of gut-brain axis in Parkinson’s disease will be presented. Clinical data from patients show a leaky gut, changed microbiome composition, enhanced markers of microbial translocation and higher levels of relevant inflammatory profiles associated with an increased expression of the pattern recognition receptor, Toll like receptor 4 (TLR4) in the colon. TLR4 plays a fundamental role in pathogen recognition and activation of the innate immune system. Both human and animal studies suggest that TLR4-mediated gut-induced neuroinflammation could play an important role in intestinal as well as central neurodegenerative processes in Parkinson’s disease. A poor gut function leads to a poor brain function; therefore targeting the microbiome and mucosal immune system with medical food interventions and/or pharmaceutical compounds could be a new approach for the therapy of CNS disorders.

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