Project title: Principles of choroid plexus-mediated brain-body interactions in the context of systemic and peripheral pathologies (ChorNEXUS)
Project No.:
Period: 1 March 2025 – 28 February 2028
Project costs: 300 000,00
Principal Investigator BMC: Dr.biol. Vita Rovīte
Cooperation partner: coordinator – Department of Clinical and Molecular Medicine; Lyon Neurosciences Research Center; German Research Cancer Center; Heidelberg University ; University Hospital Basel and University of Basel.
Project summary:
The choroid plexus (CP) is a specialized epithelial tissue located inside the brain ventricles. The CP is highly vascularized and produces cerebrospinal fluid (CSF) through transepithelial transport of water molecules. The CP also functions as the blood-CSF barrier, which controls the exchange of molecules between the periphery and the brain and provides an interface for immune surveillance in the brain. Thanks to these numerous functions, the CP is perfectly positioned for regulating bi-directional interactions between the brain and the body in health and disease. But how the CP modulates the information flow from the periphery to the brain remains poorly understood. Moreover, data on the implication of the CP in the pathophysiology of brain diseases are scarce. Finally, it remains to be identified whether CP can be targeted for clinical interventions of brain diseases.
Our goal is to unravel the overarching principles of CP-mediated brain-body interactions, identify dysfunctions of these interactions in CNS diseases of inflammatory and non-inflammatory origin, and assess the applicability of CP-targeted clinical interventions. Evidence from the literature and our consortium suggests that CP is recruited in the context of several inflammatory and non-inflammatory peripheral injuries. However, it is unclear whether CP modulation of brain function and plasticity during brainbody interactions involves common mechanisms. Our project focuses on the CP as a gateway in brainbody interactions, rather than on individual disorders, since such approach will allow us to build on the expertise gained from each disease and translate it to the other conditions to identify overarching principles.
Notably, we will study several peripheral disease conditions in preclinical animal models and humans. Our animal models include neuropathic pain which is not associated with inflammation (mouse), inflammatory pain (mouse), and postnatal systemic stress of infectious origin (rat and zebrafish). Data from EAE are available in publications from our consortium and others hence new data will not be generated.
We will then relate our preclinical models to patients with the following clinical diagnostics: chronic neuropathic pain, chronic inflammatory pain (osteoarthritis), pediatric systemic inflammation/infection and MS. By identifying the overarching role of CP in various peripheral inflammatory and noninflammatory diseases and disease models, we will provide fundamental new knowledge on the conserved role of CP as a gatekeeper of brain-body interactions and set the stage for the implementation of future clinical interventions.
Information published 03.03.2025.