International Neuroscience Meeting, Budapest 2022 – IBRO Workshop

The first brilliant demonstration of the brain-gut interactions was the cephalic phase of gastric and pancreatic secretion discovered by Ivan Pavlov. The present director of the Pavlov Institute, Ludmila Filaretova continued his work and focused on the role of the components of the stress regulatory system in the maintenance of the gastric and intestinal mucosal integrity. Indeed, during the next presentation, Dániel Kuti from Krisztina Kovács's laboratory will tell about structural, molecular and microbial changes in the gastrointestinal tract due to chronic stressors. However, this is a bidirectional link and the state of the intestinal environment can have profound effects on the activity of the central nervous system. Tamás Kozicz will present data on multi-system metabolic reprogramming as a candidate driver for increased vulnerability to psychopathologies in male mice. In the final talk you will hear about the brain-gut connections of this disorder. Namely, how trauma affects metabolism and how changes in the metabolism might influence the development of the symptoms.

Take into consideration the fact that the number of the bacteria in our body exceed the number of our own cells and the vast majority of these biologically active cells are in our gastrointestinal system — we cannot neglect this organ and its effect on our brain activity.

The symposium focuses on neuroinflammation, which plays a central role in many CNS diseases. The four topics cover important, but often overlooked aspects of this field. The role of the blood-brain barrier, which not only acts as an interface between the systemic circulation and the CNS, but participates in the pathology of several neurological diseases with neuroinflammatory components, will be discussed in two talks. Novel, unpublished data will be presented on the role of macrophage colony-stimulating factor 1 receptor (CSF1R) in cerebrovascular pathology and also on how protection of the blood-brain barrier is recognized as a pharmacological target in systemic and neuroinflammation. Another important point addressed by this symposium is the translational aspect of research related to neuroinflammation. A new, translational passive transfer-trauma model will be shown for the complex regional pain syndrome (CRPS). In this model the effect of IL-1 receptor antagonist anakinra, the soluble TNF-alpha receptor etanercept and the JAK-STAT inhibitor tofacitinib provide evidence for the contribution of neuroinflammation in CRPS-related severe, persistent pain and pointing out their therapeutic potentials in this indication. The role of glial subtypes, especially microglia, will be discussed in CRPS but further elaborated in a separate talk on how microglia-mediated processes in neurological diseases can be modulated. Both established professors and group leaders as well as young researchers are represented. Prof. Helyes, Dr. Dénes, and Prof. Deli are well-known experts in their respective fields. Dr. Campbell, an ESR grant awardee, is a rising star of the blood-brain barrier community. Dr. Walter has received last year a Junior Prima prize in Science category.

The current symposium endeavours to interrogate the contribution of neuronal subtypes to disease pathology in schizophrenia and autism spectrum disorder. Schizophrenia (SCH) and autism spectrum disorder (ASD) are chronic and serious mental illnesses which put an enormous burden on the individual, families and society. According to careful estimates there are approximately 100 million people worldwide and 170.000 in Hungary affected by SCH or ASD. The conditions have multiple genetic risk factors, possibly interplaying with several environmental risk factors. However, the neuropathology of SCH/ASD is still unclear and much remains to be discovered about the neuroanatomical correlates and causes of these conditions.

The recent development of emerging high throughput techniques such as whole genome sequencing and single nucleus RNA sequencing allowed to start to unravel the molecular mechanisms of neuropsychiatric disorders at unprecedented level. However, when applied on their own, these approaches often lose topographic information, or fail to grasp the exact architecture of neuronal circuits in which the cells of interest operate. Therefore, it is compelling to associate these with other techniques such as immunohistochemistry and in situ hybridization which enable to recognize altered gene expression in a morphological and topographical context. Also, when all these approaches are combined and complemented with in vitro assays a synergistic potential emerges which allows to achieve a comprehensive view on the pathology of SCH and ASD.

The symposium will encompass lectures which are parts of an initiative already in progress aiming to increase our understanding of the neuropathology in SCH and ASD. Coordinated efforts have been made to organize a multidisciplinary approach between research groups in order to maximize the outcome of post-mortem and in vitro neuropathological investigations. The proposed lectures range from post-mortem human investigations at cellular, proteomic and transcriptomic levels, through in vitro induced pluripotent stem cell approaches to experiments on non-human primate models in order to investigate these conditions in evolutionary context. Also, our framework has a direct translational potential as the identified cellular and molecular alterations will represent targets for future drug screening/pharmaceutical experiments.

For almost two decades, the ever-growing versatility and precision of genetic tools propelled mice into an attractive model for neuroscience. To bridge the gap between rodent and human brain, preclinical species (cats, dogs and primates) are poised to gain importance due to the recent development of new viral tools and transgenic primate lines. To treat disorders of the human brain, the link between behavior and underlying computations implemented in neuronal circuits in preclinical species needs to be better understood. The symposium focuses on computations and behavior relying on the sensory modality that is most precious to humans: vision.