Pharmacology and Brain Pathology Lab
Our research group aims at dissecting the crosstalk between the nervous and the immune system, in particular microglia cells, with the goal of unveiling its impact on synaptic activity in neurodevelopment and neurodegenerative diseases.
Nerve cells communicate with each other across small junctions called synapses. There is increasing evidence that synaptic dysfunctions are major determinants of neurodevelopment and neurodegenerative diseases – from autism spectrum disorders to Alzheimer’s disease. By understanding the role of the immune system and inflammation in synaptic dysfunctions, both during development and aging, we could pave the way to new preventive and therapeutic strategies.
Main research areas
Role of microglia in synaptic control
The group has discovered that the microglial innate immune receptor TREM2 – associated with a lethal form of early dementia and with increased risk of Alzheimer’s disease – is essential for microglia-mediated synaptic refinement during brain development. We recently showed that its absence results in impaired synapse elimination, enhanced excitatory neurotransmission, reduced long-range functional connectivity and autistic-like phenotype. We also demonstrated the mechanisms mediating the TREM2-dependent recognition of synapses to be eliminated. Lack of TREM2 also produces significant changes in the transcriptional activity of key brain cell populations. The results are starting point of the ERC Advanced Grant won by Matteoli in 2022, called MATILDA.
Inflammation and synapses development
Synapses formation during brain development is a hierarchically regulated event ensuring proper connectivity and correct excitatory/inhibitory balance in the adulthood. In a recent study, we described how transient inflammation at early developmental stages exerts a long-lasting effect on synaptogenesis. This evidence provides the first mechanistic framework for the association between prenatal inflammatory events and neurodevelopmental disorders, with implications also for babies born from Covid-19 infected mothers.
The gates protecting the brain
In the study of the immune system-to-brain communication, the role of the barriers which prevent the influx of peripheral soluble or cell components into the brain is of utmost importance. Our research focuses on the blood brain barrier: we set-up a miniaturized, bio-mimetic platform, employing human endothelial, astrocytic cells and patient-derived circulating cells, to investigate the regulation of immune trafficking across the blood brain barrier, especially under inflammatory conditions. We also demonstrated that activation of the maternal immune system causes sex-specific alterations of brain vessels in the offspring, resulting in intracerebral hemorrhagic events in the adult.