Stars in the brain and in the DBCM
Paola Bezzi appointed MER-1: understanding astrocytes by cellular imaging
The importance of astrocytes in cerebral function has been a focus of the DBCM for several years, and the recent appointment of Paola Bezzi as maître d'enseignement et de recherche-1 (MER-1) in the DBCM will strengthen this line of research. Paola Bezzi and her group have been present in the DBCM since 2004, but their stabilization will enable them to expand their research with a more long-term view, as they seek to unravel the secrets of astrocytic transmitter release and how it changes in cellular pathologies.
Transmitter exocytosis from synapses is the basis of rapid communication between neurons. By contrast, nonneuronal brain cells have generally been considered unable to perform this type of exocytosis. In collaboration with Professors Andrea Volterra, Director of the DBCM, and Vidar Gundersen (University of Oslo) since 2004, Paola Bezzi has made use of electron microscopy and new cellular imaging techniques including total internal reflection fluorescence (TIRF), to show that astrocytes possess a vesicular compartment capable of liberating glutamate following a physiological stimulation. From 2005, she has unravelled the finer details of how this atrocytic glutamate release occurs. By developing new experimental strategies and methods of analysis, the Bezzi group has been able to show, for the first time, similarities between astrocytic and neuronal transmitter release.
Liberation of gliotransmitters
These observations have likewise shown that astrocytes are very complex secretory cells with different types of organelle and chemical transmitters that vary between brain regions. Until now, Paola Bezzi has focused on astrocytic glutamate release in brain regions where neurotransmission is likewise mainly glutamatergic. She now intends to study astrocytes in other brain regions, to discover whether they are able to store and release other transmitters. “Very recently, with Robert Edwards (UCSF, USA) and Vidar Gundersen, we have got interested in the striatum and prefrontal cortex, which receive strong monoaminergic inputs, and we want to see if glia release monoamines there”, explains Paola Bezzi. Such a diversity of astrocytic transmitters would imply that the role of these cells in brain physiology is still greater than had been thought.
The role of gliotransmitters remains uncertain. To establish their importance in brain function, it will be necessary to understand in more detail the mechanisms of their liberation. The Bezzi group is therefore studying the cellular and molecular mechanisms responsible for gliotransmitter release and developing different experimental models to understand how it is affected in pathological conditions and to clarify the consequences for brain function.
Paola Bezzi collaborates with Dr. Lorenz Hirt (CHUV, Neurology) and Prof. Peter Clarke (DBCM) in translational research to study the role and behaviour of neurons and glia in cerebral ischemia, using imaging techniques (TIRF, confocal microscopy and two photon confocal microscopy) in cell cultures and in vivo. For monoamine liberation, she is collaborating with Prof Pierre Magistretti (EPFL) in a schizophrenia model where numerous alterations in monoaminergic systems have been described.
Paola Bezzi’s group includes: Julie Marchaland, Corrado Cali and Julien Gremion (doctoral students), Paola Spagnuolo (postdoc), Steeve Menétrey (technician), Giuseppe Luca (“Erasmus” student) and Ilaria Prada (doctoral student supervised jointly with the University Vita Salute, Milan).