Andrea Becchetti - Associate Professor
Department and institution: Biotechnology and Biosciences Department, University of Milano Bicocca
tel. +39 02 6448 3301
Biosketch of Andrea Becchetti
lab's website: Andrea Becchetti Research Group
institutional profile page: UNIMIB and Biotechnology and Biosciences Department
see also: PubMed, BOA
Keywords: ACh, nicotinic, cerebral cortex, hypocretin, synapse, sleep, integrin, K+ channels.
- Andrea Becchetti is currently studying the cholinergic and peptidergic regulation of local neuronal circuits in the mammalian prefrontal cortex. This modulates vigilance, cognition and the sleep-waking cycle, with pathological implications in different pathologies, such as sleep-related epilepsy and narcolepsy.
- He is also studying the regulatory interaction between voltage-gated potassium channels and integrin receptors, implicated in synaptic maturation and, outside the nervous system, in tumor growth and invasiveness.
Main research lines
We use electrophysiological, biomolecular and morphological methods to pursue the following scientific aims.
1) We study the cholinergic (especially nicotinic) and peptidergic (hypocretin/orexin) regulation of neuronal circuits in the mature mammalian prefrontal cortex and other CNS regions. This modulates vigilance, cognition and the sleep-waking cycle, with pathological implications in sleep-related pathologies.
2) Nicotinic receptors (nAChRs) also modulate synaptogenesis. Hence, we investigate the nAChR role during circuit formation (early stages of postnatal life in mice), which is important for epileptogenesis as well as the pathogenesis of other neurologic diseases.
2) In addition, we investigate the functional features of mutant nicotinic subunits (apha2 and beta2) linked to autosomal dominant sleep-related hypermotor epilepsy (also known as autosomal dominant nocturnal frontal lobe epilepsy), in both expression systems (mammalian cell lines) and murine models conditionally expressing mutant subunits.
3) Another long course project concerns the regulatory interaction between ion channels (mainly voltage-gated K+ channels) and integrin receptors, implicated in neurite extension, cell migration, tumor growth and invasiveness.
Main topics of the group
- Cholinergic regulation of synaptic transmission in the neocortex.
- Regulation by hypocretin peptides of brain function.
- Implication of the above transmitter mechanisms in the sleep-waking cycle and epilepsy.
- Ion channels in cell migration and proliferation.
Current research projects
a) Regulation of synaptic transmission in the neocortex by nicotinic receptors (collaboration with Dr. A. Amadeo) and hypocretin (orexin) peptides (collaboration with Dr. A. Vassalli).
b) Mutant nicotinic subunits in synaptogenesis and epileptogenesis.
b)Functional interaction between integrin receptors and Kv11.1 (hERG1) potassium channels (collaboration with prof. A. Arcangeli).
Internal and external collaborators
- Dr. Alida Amadeo, Department of Biosciences, University of Milano, Italy.
- Dr. Anne Vassalli, Department of Biomedical Sciences, University of Lausanne, Switzerland.
- Prof. Annarosa Arcangeli, Department of Experimental and Clinical Medicine, University of Florence, Italy.
Selected Recent Publications
Postnatal Changes in K+/Cl− Cotransporter-2 Expression in the Forebrain of Mice Bearing a Mutant Nicotinic Subunit Linked to Sleep-Related Epilepsy. Alida Amadeo, Aurora Coatti, Patrizia Aracri, Miriam Ascagni, Davide Iannantuoni, Debora Modena, Laura Carraresi, Simone Brusco, Simone Meneghini, Annarosa Arcangeli, Maria Enrica, Pasini and Andrea Becchetti. Neuroscience. 2018 Aug 21;386:91-107. doi: 10.1016/j.neuroscience.2018.06.030.
The Conformational State of hERG1 Channels Determines Integrin Association, Downstream Signaling, and Cancer Progression. Andrea Becchetti, Silvia Crescioli, Francesca Zanieri, Giulia Petroni, Raffaella Mercatelli, Stefano Coppola, Luca Gasparoli, Massimo D’Amico, Serena Pillozzi, Olivia Crociani, Matteo Stefanini, Antonella Fiore, Laura Carraresi, Virginia Morello, Sagar Manoli, Maria Felice Brizzi, Davide Ricci, Mauro Rinaldi, Alessio Masi, Thomas Schmidt, Franco Quercioli, Paola Defilippi, and Annarosa Arcangeli. Sci Signal. 2017 Apr 4;10(473):eaaf3236. doi: 10.1126/scisignal.aaf3236.
Hypocretin (Orexin) Regulates Glutamate Input to Fast-Spiking Interneurons in Layer V of the Fr2 Region of the Murine Prefrontal Cortex. Patrizia Aracri, Daniele Banfi, Maria Enrica Pasini, Alida Amadeo and Andrea Becchetti. Cereb Cortex. 2015 May;25(5):1330-47. doi: 10.1093/cercor/bht326.