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Cellular and molecular determinants of intellectual disabilities

Members

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Sector ERC

LS5_2 - Molecular and cellular neuroscience

Activity

We are interested in understanding how external stimuli may influence brain connectivity, plasticity and behavior using morphological, physiological and molecular approaches. My group has a recognized experience in studying neurological alterations caused by rare gene mutations using pre-clinical models.

During the past fifteen years, I have studied synaptic dysfunction in mouse models of Rett syndrome, a severe neurodevelopmental disorder, caused by mutations in MECP2, a methylated DNA-binding protein that regulates transcription of multiple genes.

More recently, we characterized a novel mouse model of CDKL5 Deficiency Disorder, a neurodevelopmental disease related to Rett syndrome still without a cure, with the long-term goal to serve this community of individuals and their families and to find therapeutic approaches. 

In my laboratory, we routinely combine high-resolution microscopic techniques (e.g. confocal and electron microscopy) with molecular, electrophysiological, biochemical and behavioural approaches to define the mechanistic processes underlying brain dysfunction. We have recently expanded our toolbox of experimental approaches to include in-vivo studies of selective neuronal populations in the cerebral cortex by two-photon microscopy, in-vivo Ca2+ imaging of cortical circuits with genetically-encoded indicators, viral tracing of long-range synaptic connections, and multi-electrode arrays recordings on primary cultured neurons.

 

Group’s ERC Sectors:

LS5_1 - Neuroanatomy and neurophysiology

LS5_12 - Psychiatric disorders (e.g. schizophrenia, autism, Tourette’s syndrome, obsessive compulsive disorder, depression, bipolar disorder, attention deficit hyperactivity disorder

LS5_2 - Molecular and cellular neuroscience

LS5_3 - Neurochemistry and neuropharmacology

 

Publications

Ait-Bali Y, Ba-M'hamed S, Gambarotta G, Sassoe-Pognetto M, Giustetto M, Bennis M. (2020) Pre- and postnatal exposure to glyphosate-based herbicide causes behavioral and cognitive impairments in adult mice: evidence of cortical ad hippocampal dysfunction. Archives of toxicology [DOI  PMID]

Pizzo R, Lamarca A, Sassoe-Pognetto M, Giustetto M. (2019) Structural Bases of Atypical Whisker Responses in a Mouse Model of CDKL5 Deficiency Disorder. Neuroscience [DOI  PMID]

Morello N, Schina R, Pilotto F, Phillips M, Melani R, Plicato O, Pizzorusso T, Pozzo-Miller L, Giustetto M. (2018) Loss of Mecp2 Causes Atypical Synaptic and Molecular Plasticity of Parvalbumin-Expressing Interneurons Reflecting Rett Syndrome-Like Sensorimotor Defects. eNeuro 5(5) [DOI  PMID]

Gioelli N, Maione F, Camillo C, Ghitti M, Valdembri D, Morello N, Darche M, Zentilin L, Cagnoni G, Qiu Y, Giacca M, Giustetto M, Paques M, Cascone I, Musco G, Tamagnone L, Giraudo E, Serini G. (2018) A rationally designed NRP1-independent superagonist SEMA3A mutant is an effective anticancer agent. Science translational medicine 10(442) [DOI  PMID]

Russo I, Gavello D, Menna E, Vandael D, Veglia C, Morello N, Corradini I, Focchi E, Alfieri A, Angelini C, Bianchi FT, Morellato A, Marcantoni A, Sassoe-Pognetto M, Ottaviani MM, Yekhlef L, Giustetto M, Taverna S, Carabelli V, Matteoli M, Carbone E, Turco E, Defilippi P. (2019) p140Cap Regulates GABAergic Synaptogenesis and Development of Hippocampal Inhibitory Circuits. Cerebral cortex (New York, N.Y. : 1991) 29(1) 91-105 [DOI  PMID]

Vicidomini C, Ponzoni L, Lim D, Schmeisser MJ, Reim D, Morello N, Orellana D, Tozzi A, Durante V, Scalmani P, Mantegazza M, Genazzani AA, Giustetto M, Sala M, Calabresi P, Boeckers TM, Sala C, Verpelli C. (2017) Homer1b/c clustering is impaired in Phelan-McDermid Syndrome iPSCs derived neurons. Molecular psychiatry 22(5) 637 [DOI  PMID]

Morello N, Plicato O, Piludu MA, Poddighe L, Serra MP, Quartu M, Corda MG, Giorgi O, Giustetto M. (2017) Effects of Forced Swimming Stress on ERK and Histone H3 Phosphorylation in Limbic Areas of Roman High- and Low-Avoidance Rats. PloS one 12(1) e0170093 [DOI  PMID]

Pizzo R, Gurgone A, Castroflorio E, Amendola E, Gross C, Sassoe-Pognetto M, Giustetto M. (2016) Lack of Cdkl5 Disrupts the Organization of Excitatory and Inhibitory Synapses and Parvalbumin Interneurons in the Primary Visual Cortex. Frontiers in cellular neuroscience 10 261 [DOI  PMID]

Meziane H, Khelfaoui M, Morello N, Hiba B, Calcagno E, Reibel-Foisset S, Selloum M, Chelly J, Humeau Y, Riet F, Zanni G, Herault Y, Bienvenu T, Giustetto M, Billuart P. (2016) Fasudil treatment in adult reverses behavioural changes and brain ventricular enlargement in Oligophrenin-1 mouse model of intellectual disability. Human molecular genetics 25(11) 2314-2323 [DOI  PMID]

Vicidomini C, Ponzoni L, Lim D, Schmeisser MJ, Reim D, Morello N, Orellana D, Tozzi A, Durante V, Scalmani P, Mantegazza M, Genazzani AA, Giustetto M, Sala M, Calabresi P, Boeckers TM, Sala C, Verpelli C. (2017) Pharmacological enhancement of mGlu5 receptors rescues behavioral deficits in SHANK3 knock-out mice. Molecular psychiatry 22(5) 784 [DOI  PMID]

Vicidomini C, Ponzoni L, Lim D, Schmeisser MJ, Reim D, Morello N, Orellana D, Tozzi A, Durante V, Scalmani P, Mantegazza M, Genazzani AA, Giustetto M, Sala M, Calabresi P, Boeckers TM, Sala C, Verpelli C. (2017) Pharmacological enhancement of mGlu5 receptors rescues behavioral deficits in SHANK3 knock-out mice. Molecular psychiatry 22(5) 689-702 [DOI  PMID]

Della Sala G, Putignano E, Chelini G, Melani R, Calcagno E, Michele Ratto G, Amendola E, Gross CT, Giustetto M, Pizzorusso T. (2016) Dendritic Spine Instability in a Mouse Model of CDKL5 Disorder Is Rescued by Insulin-like Growth Factor 1. Biological psychiatry 80(4) 302-311 [DOI  PMID]

Tomassy GS, Morello N, Calcagno E, Giustetto M. (2014) Developmental abnormalities of cortical interneurons precede symptoms onset in a mouse model of Rett syndrome. Journal of neurochemistry 131(1) 115-27 [DOI  PMID]

Amendola E, Zhan Y, Mattucci C, Castroflorio E, Calcagno E, Fuchs C, Lonetti G, Silingardi D, Vyssotski AL, Farley D, Ciani E, Pizzorusso T, Giustetto M, Gross CT. (2014) Mapping pathological phenotypes in a mouse model of CDKL5 disorder. PloS one 9(5) e91613 [DOI  PMID]

Ciccarelli A, Giustetto M. (2014) Role of ERK signaling in activity-dependent modifications of histone proteins. Neuropharmacology 80 34-44 [DOI  PMID]

Repetto D, Camera P, Melani R, Morello N, Russo I, Calcagno E, Tomasoni R, Bianchi F, Berto G, Giustetto M, Berardi N, Pizzorusso T, Matteoli M, Di Stefano P, Missler M, Turco E, Di Cunto F, Defilippi P. (2014) p140Cap regulates memory and synaptic plasticity through Src-mediated and citron-N-mediated actin reorganization. The Journal of neuroscience : the official journal of the Society for Neuroscience 34(4) 1542-53 [DOI  PMID]

Arroyo AI, Camoletto PG, Morando L, Sassoe-Pognetto M, Giustetto M, Van Veldhoven PP, Schuchman EH, Ledesma MD. (2014) Pharmacological reversion of sphingomyelin-induced dendritic spine anomalies in a Niemann Pick disease type A mouse model. EMBO molecular medicine 6(3) 398-413 [DOI  PMID]

Marcello E, Saraceno C, Musardo S, Vara H, de la Fuente AG, Pelucchi S, Di Marino D, Borroni B, Tramontano A, Perez-Otano I, Padovani A, Giustetto M, Gardoni F, Di Luca M. (2013) Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease. The Journal of clinical investigation 123(6) 2523-38 [DOI  PMID]

Ciccarelli A, Calza A, Santoru F, Grasso F, Concas A, Sassoe-Pognetto M, Giustetto M. (2013) Morphine withdrawal produces ERK-dependent and ERK-independent epigenetic marks in neurons of the nucleus accumbens and lateral septum. Neuropharmacology 70 168-79 [DOI  PMID]

Katz DM, Berger-Sweeney JE, Eubanks JH, Justice MJ, Neul JL, Pozzo-Miller L, Blue ME, Christian D, Crawley JN, Giustetto M, Guy J, Howell CJ, Kron M, Nelson SB, Samaco RC, Schaevitz LR, St Hillaire-Clarke C, Young JL, Zoghbi HY, Mamounas LA. (2012) Preclinical research in Rett syndrome: setting the foundation for translational success. Disease models & mechanisms 5(6) 733-45 [DOI  PMID]

Ciccarelli A, Calza A, Panzanelli P, Concas A, Giustetto M, Sassoe-Pognetto M. (2012) Organization of GABAergic synaptic circuits in the rat ventral tegmental area. PloS one 7(10) e46250 [DOI  PMID]

Chapleau CA, Boggio EM, Calfa G, Percy AK, Giustetto M, Pozzo-Miller L. (2012) Hippocampal CA1 pyramidal neurons of Mecp2 mutant mice show a dendritic spine phenotype only in the presymptomatic stage. Neural plasticity 2012 976164 [DOI  PMID]

Landi S, Putignano E, Boggio EM, Giustetto M, Pizzorusso T, Ratto GM. (2011) The short-time structural plasticity of dendritic spines is altered in a model of Rett syndrome. Scientific reports 1 45 [DOI  PMID]

Lopez-Atalaya JP, Ciccarelli A, Viosca J, Valor LM, Jimenez-Minchan M, Canals S, Giustetto M, Barco A. (2011) CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement. The EMBO journal 30(20) 4287-98 [DOI  PMID]

Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT. (2011) Synaptic pruning by microglia is necessary for normal brain development. Science (New York, N.Y.) 333(6048) 1456-8 [DOI  PMID]

Ricciardi S, Boggio EM, Grosso S, Lonetti G, Forlani G, Stefanelli G, Calcagno E, Morello N, Landsberger N, Biffo S, Pizzorusso T, Giustetto M, Broccoli V. (2011) Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model. Human molecular genetics 20(6) 1182-96 [DOI  PMID]

Epis R, Marcello E, Gardoni F, Vastagh C, Malinverno M, Balducci C, Colombo A, Borroni B, Vara H, Dell'Agli M, Cattabeni F, Giustetto M, Borsello T, Forloni G, Padovani A, Di Luca M. (2010) Blocking ADAM10 synaptic trafficking generates a model of sporadic Alzheimer's disease. Brain : a journal of neurology 133(11) 3323-35 [DOI  PMID]

Pavlowsky A, Zanchi A, Pallotto M, Giustetto M, Chelly J, Sala C, Billuart P. (2010) Neuronal JNK pathway activation by IL-1 is mediated through IL1RAPL1, a protein required for development of cognitive functions. Communicative & integrative biology 3(3) 245-7 [DOI  PMID]

Rust MB, Gurniak CB, Renner M, Vara H, Morando L, Gorlich A, Sassoe-Pognetto M, Banchaabouchi MA, Giustetto M, Triller A, Choquet D, Witke W. (2010) Learning, AMPA receptor mobility and synaptic plasticity depend on n-cofilin-mediated actin dynamics. The EMBO journal 29(11) 1889-902 [DOI  PMID]

Lonetti G, Angelucci A, Morando L, Boggio EM, Giustetto M, Pizzorusso T. (2010) Early environmental enrichment moderates the behavioral and synaptic phenotype of MeCP2 null mice. Biological psychiatry 67(7) 657-65 [DOI  PMID]

Pavlowsky A, Gianfelice A, Pallotto M, Zanchi A, Vara H, Khelfaoui M, Valnegri P, Rezai X, Bassani S, Brambilla D, Kumpost J, Blahos J, Roux MJ, Humeau Y, Chelly J, Passafaro M, Giustetto M, Billuart P, Sala C. (2010) A postsynaptic signaling pathway that may account for the cognitive defect due to IL1RAPL1 mutation. Current biology : CB 20(2) 103-15 [DOI  PMID]

Boggio EM, Lonetti G, Pizzorusso T, Giustetto M. (2010) Synaptic determinants of rett syndrome. Frontiers in synaptic neuroscience 2 28 [DOI  PMID]

Vara H, Onofri F, Benfenati F, Sassoe-Pognetto M, Giustetto M. (2009) ERK activation in axonal varicosities modulates presynaptic plasticity in the CA3 region of the hippocampus through synapsin I. Proceedings of the National Academy of Sciences of the United States of America 106(24) 9872-7 [DOI  PMID]

Fasano S, D'Antoni A, Orban PC, Valjent E, Putignano E, Vara H, Pizzorusso T, Giustetto M, Yoon B, Soloway P, Maldonado R, Caboche J, Brambilla R. (2009) Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) controls activation of extracellular signal-regulated kinase (ERK) signaling in the striatum and long-term behavioral responses to cocaine. Biological psychiatry 66(8) 758-68 [DOI  PMID]

Camoletto PG, Vara H, Morando L, Connell E, Marletto FP, Giustetto M, Sassoe-Pognetto M, Van Veldhoven PP, Ledesma MD. (2009) Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18. PloS one 4(4) e5310 [DOI  PMID]

Boggio EM, Putignano E, Sassoe-Pognetto M, Pizzorusso T, Giustetto M. (2007) Visual stimulation activates ERK in synaptic and somatic compartments of rat cortical neurons with parallel kinetics. PloS one 2(7) e604 [DOI  PMID]

Pilo Boyl P, Di Nardo A, Mulle C, Sassoe-Pognetto M, Panzanelli P, Mele A, Kneussel M, Costantini V, Perlas E, Massimi M, Vara H, Giustetto M, Witke W. (2007) Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior. The EMBO journal 26(12) 2991-3002 [DOI  PMID]

Si K, Giustetto M, Etkin A, Hsu R, Janisiewicz AM, Miniaci MC, Kim JH, Zhu H, Kandel ER. (2003) A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia. Cell 115(7) 893-904 [DOI  PMID]

Giustetto M, Hegde AN, Si K, Casadio A, Inokuchi K, Pei W, Kandel ER, Schwartz JH. (2003) Axonal transport of eukaryotic translation elongation factor 1alpha mRNA couples transcription in the nucleus to long-term facilitation at the synapse. Proceedings of the National Academy of Sciences of the United States of America 100(23) 13680-5 [DOI  PMID]

Guan Z, Giustetto M, Lomvardas S, Kim JH, Miniaci MC, Schwartz JH, Thanos D, Kandel ER. (2002) Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure. Cell 111(4) 483-93 [DOI  PMID]

Bailey CH, Giustetto M, Huang YY, Hawkins RD, Kandel ER. (2000) Is heterosynaptic modulation essential for stabilizing Hebbian plasticity and memory? Nature reviews. Neuroscience 1(1) 11-20 [DOI  PMID]

Bartsch D, Ghirardi M, Casadio A, Giustetto M, Karl KA, Zhu H, Kandel ER. (2000) Enhancement of memory-related long-term facilitation by ApAF, a novel transcription factor that acts downstream from both CREB1 and CREB2. Cell 103(4) 595-608 [DOI  PMID]

Bailey CH, Giustetto M, Zhu H, Chen M, Kandel ER. (2000) A novel function for serotonin-mediated short-term facilitation in aplysia: conversion of a transient, cell-wide homosynaptic hebbian plasticity into a persistent, protein synthesis-independent synapse-specific enhancement. Proceedings of the National Academy of Sciences of the United States of America 97(21) 11581-6 [DOI  PMID]

Casadio A, Martin KC, Giustetto M, Zhu H, Chen M, Bartsch D, Bailey CH, Kandel ER. (1999) A transient, neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis. Cell 99(2) 221-37 [DOI  PMID]

Sassoe-Pognetto M, Giustetto M, Panzanelli P, Cantino D, Kirsch J, Fritschy JM. (1999) Postsynaptic colocalization of gephyrin and GABAA receptors. Annals of the New York Academy of Sciences 868 693-6 [DOI  PMID]

Quaglino E, Giustetto M, Panzanelli P, Cantino D, Fasolo A, Sassoe-Pognetto M. (1999) Immunocytochemical localization of glutamate and gamma-aminobutyric acid in the accessory olfactory bulb of the rat. The Journal of comparative neurology 408(1) 61-72 [DOI  PMID]

Giustetto M, Kirsch J, Fritschy JM, Cantino D, Sassoe-Pognetto M. (1998) Localization of the clustering protein gephyrin at GABAergic synapses in the main olfactory bulb of the rat. The Journal of comparative neurology 395(2) 231-44 [DOI  PMID]

Giustetto M, Bovolin P, Fasolo A, Bonino M, Cantino D, Sassoe-Pognetto M. (1997) Glutamate receptors in the olfactory bulb synaptic circuitry: heterogeneity and synaptic localization of N-methyl-D-aspartate receptor subunit 1 and AMPA receptor subunit 1. Neuroscience 76(3) 787-98 [DOI  PMID]

Sassoe-Pognetto M, Cantino D, Panzanelli P, Verdun di Cantogno L, Giustetto M, Margolis FL, De Biasi S, Fasolo A. (1993) Presynaptic co-localization of carnosine and glutamate in olfactory neurones. Neuroreport 5(1) 7-10 [DOI  PMID]

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