Research topics

Our laboratory has a long-lasting experience in the study of glial cells functions, many of which are carried out through different purinergic receptors, suggesting that they could be exploited to study the mechanisms at the basis of physiological and pathological conditions. It is in fact recognized that glial cells, both in the CNS and PNS, provide mechanical, metabolic and trophic support to neurons and participate in neurotrasmission, affecting neuronal differentiation, proliferation and death. Our research activity is focused on:

A) The role of the P2Y-like receptor GPR17 and its ligands in the regulation of oligodendrocyte precursor cell (OPC) differentiation under physiological conditions and in several animal models of demyelinating diseases, such as cerebral ischemia, multiple sclerosis and amyotrophic lateral sclerosis.

B) The identification of the mechanisms underlying OPC differentiation under physiological and pathological conditions, with a specific focus on micro-RNAs and microglia-derived extracellular vesicles.

C) The study of neuron-glia communication in the CNS and PNS in different in vivo models of trigeminal pain, including a rat model of experimental autoimmune encephalomyelitis (EAE) for the study of multiple sclerosis-associated trigeminal pain.

D) The identification of new molecules acting on GPR17 using computational approaches, including 3D modeling, in silico virtual screening, medicinal chemistry optimization and dissociation constant prediction.

Techniques

Molecular biology (cloning, gene silencing, siRNA, miRNA, mutagenesis, qRT-PCR)

Cell cultures: primary cultures of astrocytes, oligodendrocytes, microglia, DRG, satellite glial cells, pericytes, brain endothelial cells

In situ hybridization, immunocytochemistry, immunohistochemistry

Cells sorting of oligodendrocytes and microglia from neonatal and adult mouse tissues (MACS)

Biochemical and functional assays (evaluation of luciferase activity, in vitro hypoxia/ischemia, cytotoxicity, proliferation and migration, caspase activity)

In vivo:
- GPR17-iCreER^T2xCAG-eGFP fluorescent mouse line
- Rodent experimental autoimmune encephalomyelitis (EAE)
- Murine demyelination (cuprizone and lysolecithin)
- Rat inflammatory trigeminal pain with Complete Freund Adjuvant
- Rodent neuropathic trigeminal pain (infra-orbital nerve ligation)
- Behavioral tests with von Frey filaments

Confocal microscopy, time lapse videomicroscopy

Molecular modelling, computational chemistry

Collaborators

- Prof. Lars Arendt-Nielsen, Aalborg University (Denmark)
- Dr. Enrica Boda, Dr. Annalisa Buffo, University of Turin
- Prof. Roberta Brambilla, University of Miami (USA)
- Prof. Giambattista Bonanno, University of Genoa
- Prof. Enrica Calleri, University of Pisa
- Dr. Leda Dimou, Ulm University (Germany)
- Prof. Ivano Eberini, University of Milan
- Dr. Roberto Furlan, Prof. Gianvito Martino, San Raffaele Research Institute, Milan
- Dr. Rosaria Greco, Mondino National Neurological Institute Foundation, Pavia
- Dr. Pierre Gressens, Inserm, Paris (Francia)
- Prof. Nico Mitro, University of Milan
- Prof. Cesare Patrone, Karolinska Institute, Stockholm (Sweden)
- Prof. Katia Petroni, University of Milan
- Prof. Marco Salvetti, University of Rome
- Prof. Luigi Sironi, University of Milan
- Prof. Letizia Trincavelli, University of Pisa
- Prof. Arn van den Maagdenberg, Leiden University (Netherlands)
- Prof. Marco Ventura, University of Parma
- Dr. Claudia Verderio, CNR (Milan)

Selected publications

1. Coppolino GT, Marangon D, Negri C, Menichetti G, Fumagalli M, Gelosa P, Dimou L, Furlan R, Lecca D, Abbracchio MP (2018) Differential local tissue permissiveness influences the final fate of GPR17-expressing oligodendrocyte precursors in two distinct models of demyelination. Glia 66:1118-1130
2. Bonfanti E, Gelosa P, Fumagalli M, Dimou L, Vigano F, Tremoli E, Cimino M, Sironi L, Abbracchio MP (2017) The role of oligodendrocyte precursor cells expressing the GPR17 receptor in brain remodeling after stroke. Cell death & disease 8:e2871
3. Lecca D, Marangon D, Coppolino GT, Mendez AM, Finardi A, Costa GD, Martinelli V, Furlan R, Abbracchio MP (2016) MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis. Scientific reports 6:34503
4. Magni G, Merli D, Verderio C, Abbracchio MP, Ceruti S (2015) P2Y2 receptor antagonists as anti-allodynic agents in acute and sub-chronic trigeminal sensitization: role of satellite glial cells. Glia 63:1256-1269
5. Calleri E, Ceruti S, Cristalli G, Martini C, Temporini C, Parravicini C, Volpini R, Daniele S, Caccialanza G, Lecca D, et al.(2010) Frontal affinity chromatography-mass spectrometry useful for characterization of new ligands for GPR17 receptor. Journal of medicinal chemistry 53:3489-3501