Dr Claudia Verderio is currently non-tenured professor of pharmacology at University Vita e Salute HSR, Milan, Italy. In addition, she works as senior researcher for CNR Institute of Neuroscience, Milan.
She received her PhD in Experimental Pharmacotherapy from the University of Brescia, Italy, during which time she spent one year as visiting scientist at the Department of Cell Biology, Yale University of Medicine, USA.
Since 1994 Dr Verderio’s research interest has been focused on mechanisms of intercellular communications within the brain in physiological and pathological conditions. Her recent work has paid particular attention to a novel mechanism of intercellular communication based on release of extracellular vesicles, on the role of microvesicles in the pathogenesis of neuroinflammatory and degenerative diseases, and on their potential as disease biomarkers.
Driving microglia metabolism towards remyelination and restoration of brain damage in multiple sclerosis
Neuroinflammation plays a central role in multiple sclerosis (MS) by impairing remyelination and causing neuronal injury. Microglia orchestrate the brain’s inflammatory response, and contribute to the onset and outcome of MS, including secondary progressive phases. Despite a negative impact of microglia activation on myelination, current knowledge indicates that alternatively activated microglia may be beneficial in MS. However, the cellular mechanisms governing the transition of microglia from inflammatory to pro-regenerative functions are poorly understood. Metabolic features of microglia states have not been investigated although metabolic activities co-define effector states in various cells and are likely to control production of extracellular vesicles (EVs), which are key mediators of intercellular communication. Recent data indicate that conditioning with mesenchymal stem cells (MSC) is effective in directing microglia toward pro-regenerative functions, as expressed by EV-mediated enhancement of myelination of rodent oligodendrocyte progenitor cells.
We will investigate how conditioning with MSC impacts on microglia metabolism and EV-dependent microglia/oligodendrocyte crosstalk in the lysolecithin mouse model of demyelination, with the goal of identifying strategies to modulate the phenotype of microglia in humans.
Specific goals are: i) to fully establish the MSC-mediated promotion of a pro-regenerative microglia phenotype by confirming that EVs released from MSC-conditioned microglia enhance oligodendrocyte recruitment, proliferation and differentiation in mice injected with lysolecithin; ii) to assess changes induced in pro-regenerative microglia by MSC exposure using metabolomic analysis and understand how these metabolic activities affect EV production; iii) to manipulate specific metabolic pathways by genetic or pharmacological approaches to determine their beneficial action on in vivo remyelination.
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