Research Group

Matteoli Group

Pharmacology and Brain Pathology Lab

Matteoli Group

Michela Matteoli

Group Leader

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.

The challenge

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.

Selected publications

Borreca A
Brain Behav Immun
Loss of interleukin 1 signaling causes impairment of microglia- mediated synapse elimination and autistic-like behaviour in mice.
Tagliatti E
Immunity
Trem2 expression in microglia is required to maintain normal neuronal bioenergetics during development.
Rasile M
EMBO J
Maternal immune activation leads to defective brain-blood vessels and intracerebral hemorrhages in male offspring.
Paolicelli RC
Neuron
Microglia states and nomenclature: A field at its crossroads.
Mirabella F
Immunity
Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring.
Carloni S
Science
Identification of a choroid plexus vascular barrier closing during intestinal inflammation.
Pizzamiglio L
JCI Insight
The DNA repair protein ATM as a target in autism spectrum disorder.
Pozzi D
Transl Psychiatry
Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on?
Scott-Hewitt N
EMBO J
Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia.
Ghirardini E
PLoS Pathog
Mutant prion proteins increase calcium permeability of AMPA receptors, exacerbating excitotoxicity.
Fossati G
EMBO J
Pentraxin 3 regulates synaptic function by inducing AMPA receptor clustering via ECM remodeling and β1-integrin.
Filipello F
Immunity
The Microglial Innate Immune Receptor TREM2 Is Required for Synapse Elimination and Normal Brain Connectivity.
Tomasoni R
Elife
Lack of IL-1R8 in neurons causes hyperactivation of IL-1 receptor pathway and induces MECP2-dependent synaptic defects.
Fossati G
Cell Death Differ
Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis.
Antonucci F
EMBO Rep
Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses.
Menna E
EMBO J
Eps8 controls dendritic spine density and synaptic plasticity through its actin-capping activity.
Tomasoni R
Nat Commun
SNAP-25 regulates spine formation through postsynaptic binding to p140Cap.
Senatore A
Neuron
Mutant PrP suppresses glutamatergic neurotransmission in cerebellar granule neurons by impairing membrane delivery of VGCC α(2)δ-1 Subunit.
Antonucci F
J Neurosci
Cracking down on inhibition: selective removal of GABAergic interneurons from hippocampal networks.

Group members

Matteoli Group
Sebastiano Bariselli

Assistant professor, Humanitas University

Matteoli Group
Giulia Bertoni

PhD student

Matteoli Group
Matteo Bizzotto

Postdoc fellow

Matteoli Group
Antonella Borreca

CNR Researcher

Matteoli Group
Irene Corradini

CNR Researcher

Matteoli Group
Genni Desiato

Postdoc fellow

Matteoli Group
Chiara Elia

CNR Technologist

Matteoli Group
Elisa Faggiani

Technician

Matteoli Group
Fabia Filipello

Postdoc fellow

Matteoli Group
Alessandra Folci

CNR Researcher

Matteoli Group
Giuliana Fossati

Postdoc fellow

Matteoli Group
Edoardo Fraviga

PhD student

Matteoli Group
Riccardo Grassi

PhD student

Matteoli Group
Lucia Iannotta

Postdoc fellow

Matteoli Group
Eliana Lauranzano

Postdoc fellow

Matteoli Group
Marianna Leonzino

CNR Researcher

Matteoli Group
Maria Luisa Malosio

CNR Senior Researcher

Matteoli Group
Michela Matteoli

Group Leader

Matteoli Group
Chiara Mazzola

Postdoc fellow

Matteoli Group
Elisabetta Menna

CNR Senior Researcher

Matteoli Group
Raffaella Morini

Staff scientist

Matteoli Group
Lorena Passoni

Postdoc fellow

Matteoli Group
Marco Pizzocri

Postdoc fellow

Matteoli Group
Davide Pozzi

Head of Unit

Matteoli Group
Marco Rasile

Assistant professor, Humanitas University

Matteoli Group
Margherita Ravanelli

PhD student

Matteoli Group
Alessandro Rossi

Postdoc fellow
Bioinformatician

Matteoli Group
Chiara Saulle

PhD student

Matteoli Group
Alessia Seccia

PhD student

Matteoli Group
Arianna Sironi

PhD student

Matteoli Group
Elisabetta Stanzani

Postdoc fellow

Matteoli Group
Erika Tagliatti

Postdoc fellow

Matteoli Group
Matteo Tamborini

Postdoc fellow

Matteoli Group
Cecilia Zen

PhD student