Our research aims at investigating the molecular basis of autism and epilepsy, two brain disorders of proven neurodevelopmental origin whose cellular and molecular causes remain largely unknown. We use a multidisciplinary approach, ranging from pharmacological to genetic animal models, to study autism and epilepsy.
Specific projects are:
- Developmental bases of autism. We study how the altered expression of neural genes during embryonic brain development can impact autistic-like behaviours during postnatal life. We extensively studied mice lacking the homeobox-containing gene Engrailed-2 (En2-/- mice), showing that these mice have anatomical and molecular defects of GABAergic interneurons. Our current research aims to identify the behavioural outcomes of GABAegic neuron dysfunction in En2-/- mice, and the gene-expression pathways that are commonly altered in En2-/- mice and other mouse models of autism.
- Role of inflammation in epilepsy. We investigate the molecular mechanisms through which systemic or brain inflammation can impact seizure development and gene expression pathways. Our recent studies demonstrate a crucial role of the chemokine CCL2 in inflammation-induced seizures. Pharmacological blockade of CCL2 synthesis or CCR2 receptor signalling significantly reduces seizures enhanced by systemic inflammation.
Our research group is currently located at the Centre for Integrative Biology of the University of Trento.
My work focuses on the molecular bases of neurodevelopmental disorders, with a specific interest in mouse models of autism and epilepsy.
I am Professor of Physiology at CIMeC since February 2017, and coordinator of TRAIN (Trentino Autism Initiative). I obtained my Ph.D. in Neurobiology at Scuola Normale Superiore (Pisa, Italy) in 1996, and did my postdoc at IGBMC (Strasbourg, France) from 1996 to 1999. In 2000, I joined the CNR Neuroscience Institute (Pisa, Italy) as a research scientist. In 2009 I moved my laboratory to the Centre for Integrative Biology (CIBIO) of the University of Trento (Italy). He is member of the Directive Council of the Italian Neuroscience Society (SINS), and editorial board member of Neuroscience (the official journal of IBRO – International Brain research organization), Epilepsy Research and Journal of Neurodevelopmental Disorders.
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Selected publications (2009-2017) – Full list available in PubMed
- Provenzano G, Chelini G., Bozzi Y (2016) "Genetic control of social behaviour: lessons from mutant mice”. Behav Brain Res. 2016 Nov 4. pii: S0166-4328(16)31002-6. doi: 10.1016/j.bbr.2016.11.005. [Epub ahead of print] PMID: 27825935
- Provenzano G, Corradi Z, Monsorno K, Fedrizzi T, Ricceri L, Scattoni ML, Bozzi Y (2016) "Comparative gene expression analysis of two mouse models of autism: transcriptome profiling of the BTBR and En2-/- hippocampus", Front Neurosci. 2016 Aug 25;10:396. doi: 10.3389/fnins.2016.00396. eCollection 2016.
- Bozzi Y., Caleo M. (2016) Epilepsy, seizures and inflammation: role of the C-C motif ligand 2 chemokine. DNA Cell Biol. 2016 May 11. [Epub ahead of print] DOI: 10.1089/dna.2016.3345. PMID:27167681
- Zunino G., Messina A., Sgadò P., Baj G., Casarosa S., Bozzi Y. (2016). Brain-derived neurotrophic factor signaling is altered in the forebrain of Engrailed-2 knockout mice. Neuroscience 324: 252–261. pii: S0306-4522(16)00246-3. doi: 10.1016/j.neuroscience.2016.03.023. PMID:26987954
- Cerri C., Genovesi S., Allegra M., Pistillo F., Püntener U., Guglielmotti A., Perry V.H., Bozzi Y.*, Caleo M.* (2016) The chemokine CCL2 mediates the seizure enhancing effects of systemic inflammation (*equal contribution as senior authors). The Journal of Neuroscience, 36:3777-3788; doi:10.1523/JNEUROSCI.0451-15.2016
- Provenzano G, Sgadò P, Genovesi S, Zunino G, Casarosa S, Bozzi Y (2015). Hippocampal dysregulation of FMRP/mGluR5 signaling in Engrailed-2 knockout mice, a model of autism spectrum disorders. Neuroreport 26:1101-1105. doi: 10.1097/WNR.0000000000000477.
- Messina A., Lan L., Incitti T. Bozza A., Andreazzoli A., Vignali R. Cremisi F., Bozzi Y., Casarosa S. (2015) Noggin-mediated retinal induction reveals a novel interplay between BMP inhibition, TGF-β and SHH. Stem Cells Aug;33(8):2496-508. doi: 10.1002/stem.2043. Epub 2015 May 26.
- Tripathi P.P., Bozzi Y. (2015) The role of dopaminergic and serotonergic systems in neurodevelopmental disorders: a focus on epilepsy and seizure susceptibility. Bioimpacts. 5(2):97-102. doi: 10.15171/bi.2015.07.
- Provenzano G., Pangrazzi L., Poli A., Berardi N., Bozzi Y. (2015) Immunohistochemical visualization of hippocampal neuron activity after spatial learning in a mouse model of neurodevelopmental disorders. Journal of Visualized Experiments (JoVE). 2015 May 12;(99). doi: 10.3791/52919.
- Canitano R., Bozzi Y. (2015) New treatment perspectives in autism spectrum disorders. Front Pediatr. 3:22. doi: 10.3389/fped.2015.00022.
- Provenzano G., Pangrazzi L., Poli A., Sgadò P., Berardi N., Bozzi Y. (2015) Reduced phosphorylation of synapsin I in the hippocampus of Engrailed-2 knockout mice, a model for autism spectrum disorders. Neuroscience 286:122-30. doi: 10.1016/j.neuroscience.2014.11.041.
- Deidda G., Allegra M., Cerri C., Naskar S., Bony G, Zunino G, Bozzi Y, Caleo M, Cancedda L (2015) Early depolarizing GABA controls critical period plasticity in the rat visual cortex. Nat Neurosci. 18(1):87-96. doi: 10.1038/nn.3890.
- Curatolo P, Ben-Ari Y, Bozzi Y, Catania MV, D‘Angelo E, Mapelli L, Oberman LM, Rosenmund C and Cherubini E (2014). Synapses as therapeutic targets for Autism Spectrum Disorders: an International Symposium held in Pavia on July 4th, 2014. Front. Cell. Neurosci. 8:309. doi: 10.3389/fncel.2014.00309.
- Provenzano G., Clementi E., Genovesi S., Scali M., Tripathi P.P., Sgadò P., Bozzi Y. (2014) GH dysfunction in Engrailed-2 knockout mice, a model for autism spectrum disorders. Front.Pediatr. 2:92. doi: 10.3389/fped.2014.00092.
- Provenzano G, Pangrazzi L, Poli A, Sgadò P, Genovesi S, Zunino G, Berardi N, Casarosa S, Bozzi Y (2014) Hippocampal dysregulation of neurofibromin-dependent pathways is associated with impaired spatial learning in Engrailed 2 knockout mice. The Journal of Neuroscience, 1 October 2014, 34(40): 13281-13288; doi: 10.1523/JNEUROSCI.2894-13.2014
- Allegra M, Genovesi S, Maggia M, Cenni MC, Zunino G, Sgadò P, Caleo M. Bozzi Y (2014) Altered GABAergic markers, increased binocularity and reduced plasticity in the visual cortex of Engrailed-2 knockout mice. Front Cell Neurosci. 2014 Jun 17;8:163. doi: 10.3389/fncel.2014.00163.
- Sgadò P, Provenzano G, Dassi E, Adami V, Zunino G, Genovesi S, Casarosa S, Bozzi Y (2013) Transcriptome profiling in Engrailed2 knockout mice reveals common molecular pathways associated with ASD. Molecular Autism, 4:51 doi:10.1186/2040-2392-4-51.
- Bozzi Y, Borrelli E (2013) The role of dopamine signaling in epileptogenesis. Front. Cell. Neurosci. 7:157. doi: 10.3389/fncel.2013.00157
- Sgadò P, Genovesi S, Kalinovsky A, Zunino G, Macchi F, Allegra M, Murenu E, Provenzano G, Tripathi PP, Casarosa S, Joyner AL, Bozzi Y. (2013) Loss of GABAergic neurons in the hippocampus and cerebral cortex of Engrailed-2 null mutant mice: Implications for autism spectrum disorders. Exp Neurol. 247:496-505. doi: 10.1016/j.expneurol.2013.01.021.
- Corradini I, Donzelli A, Antonucci F, Welzl H, Loos M, Martucci R, De Astis S, Pattini L, Inverardi F, Wolfer D, Caleo M, Bozzi Y, Verderio C, Frassoni C, Braida D, Clerici M, Lipp HP, Sala M, Matteoli M (2012) Epileptiform activity and cognitive deficits in SNAP-25+/- are normalized by antiepileptic drugs. Cereb Cortex 24(2):364-76. doi: 10.1093/cercor/bhs316.
- Provenzano G., Zunino G., Genovesi S., Sgadò P., Bozzi Y. (2012) Mutant mouse models of autism spectrum disorders. Disease Markers 33(5);225-239 (Special Issue on “Gene expression studies in autism”).
- Bozzi Y, Casarosa S, Caleo M (2012) Epilepsy as a neurodevelopmental disorder. Frontiers in Psychiatry 3:19.
- Sgadò P, Dunleavy M, Genovesi S, Provenzano G, Bozzi Y (2011) The role of GABAergic system in neurodevelopmental disorders: a focus on autism and epilepsy. Int J Physiol Pathophysiol Pharmacol 3:223-235.
- Bozzi Y, Dunleavy M, Henshall D (2011). Cell signaling underlying epileptic behavior. Front. Behav. Neurosci. 5:45.
- Tripathi PP, Sgadò P, Scali M, Viaggi C, Casarosa S, Simon H, Vaglini F, Corsini GU, Bozzi Y (2009) Increased susceptibility to kainic acid-induced seizures in Engrailed-2 knockout mice. Neuroscience 159:842-9.
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TRAIN – Trentino Autism Initiative. Yuri Bozzi is the coordinator of TRAIN, a multidisciplinary network on autism research.