Paola Sgadò
Ricercatore
Dipartimento di Biologia Cellulare, Computazionale e Integrata - CIBIO
Formazione |
|
|
|
Carriera accademica ed attività didattica |
|
|
|
Interessi di ricerca |
|
My research aims at exploring the effect of ASD-related alterations (both pharmacological and genetical) on the development of social skills in domestic chicks, and in particular on the study of social predispositions, early social-orienting mechanisms emerging in the first hours after birth in humans as well as domestic chicks. We found that VPA, an anticonvulsant previously shown to increase the risk of ASD, changes the chicks’ early-social orienting mechanisms, without affecting basic brain functions, such as motor control and filial imprinting. We are currently broadening the study of social predispositions affected by VPA and analyzing the neurobiological bases of these deficits, to identify relevant brain areas, neurotransmitter systems and molecular pathways necessary for the expression of social predispositions in chicks. To my knowledge the chick VPA model is the first to link ASD-relevant behavioral deficits induced by VPA with behavioral task that are analogous to human social behavior. We are also developing gene editing strategies in domestic chicks to induce gene alterations relevant for ASD and test the effect of ASD-associated gene mutation on the development of social-orienting mechanisms in domestic chicks. We believe that the study of the brain circuits and the gene networks involved in social predispositions in chicks, and affected by ASD- inducing pharmacological or genetic manipulations, may potentially shed light on the earliest disturbances and the neurobiological bases of ASD. Using this novel class of inter-species social-orienting mechanisms and ASD-modelling in domestic chicks, we believe we present a new tool of potential translational value to investigate the mechanistic bases of ASD social deficits with the aid of early behavioural markers analogous to those used in human studies.
|
|
Attività di ricerca |
|
Jan’17 – present Principal Investigator at the Molecular and Cellular Cognition (mc2) group investigating the molecular and cellular components of cognitive processes. The research is mainly focused on the molecular bases of social cognition and their link to neurodevelopmental disorders, using a combination of behavioural, neurobiological and molecular techniques. Jul ’15 – Dec ’16 PostDoc research experience on “Neurobiological bases of animal behaviour” at the Centre for Mind/Brain Science, University of Trento. The research aimed to study the neurobiological mechanisms underlying animal behavior using a combination of behavioural and neurobiological technique such as the expression of immediate early genes, electrophysiology, anatomy and molecular genetics. Jul ’10 – Dec ’14 Marie Curie COFUND Incoming PostDoc 2009; EnCORT Project. Project title: “Neurodevelopmental bases of ASD: cortical inhibitory system development in En2 knockout mice” at the Centre for Integrative Biology, University of Trento. The project aimed at analysing the effect of En2 mutation in the development of GABAergic interneurons. We found a significant loss of PV interneurons in the sensory cortices of En2 mutants already at postnatal day 10, accompanied by molecular alterations in the expression of ASD-related genes (Fmr1, mGluR5, BDNF and KCC2). Data suggest delayed maturation of cortical circuits in En2 mice and altered sensory processing and integration in these mice. Moreover, our transcriptome analysis revealed that En2 regulates a complex network of ASD-related genes, confirming and expanding the idea that ASD results from alterations of conserved transcriptional pathways. Jun ’09 – Jun ’10 PostDoc research experience on “Neuroanatomical characterization of the En2 knock-out mice, a model for autistic spectrum disorders” at the Molecular Neuropathology lab, Centre for Integrative Biology, University of Trento, (Head Dr. Y. Bozzi). The project involved the set up a new research line regarding the characterization of En2 mutant phenotype in the forebrain. The results strengthen the hypothesis of a prominent role of GABAergic interneurons in the pathogenesis of ASD. Jun ’07 – May ’09 PostDoc research experience on “Malformation of cortical development and epilepsy: genotype-phenotype correlation” at the Neurogenetics Lab, Child Neurology Unit, “A. Meyer” Children’s Hospital, Florence (Head Prof. R. Guerrini). The project aim was to identify new candidate genes for cortical malformations syndromes and to perform genotype-phenotype correlation using in utero electroporation and RNAi in rats [in collaboration with Dr. Carlos Cardoso at INSERM/INMED, Marseille]. May ’05 – May ’07 PostDoc research experience on “New experimental models for Parkinson’s disease” at the Neuroscience Department, University of Pisa (Head Prof. G.U. Corsini). Aim of the study was to investigate pre-symptomatic compensatory changes occurring in the brain upon chronic long-lasting degeneration. We assessed neurochemical, behavioural and electrophysiogical changes in young and aged EnHT mice. Data suggest that, despite the early degeneration of DA cell bodies, frank behavioral deficits and synaptic plasticity alterations appear only in old mice and that the extracellular metabolism may have a prominent role in the establishment of these compensatory changes. Overall the study suggest the EnHT mouse as a key model of nigrostriatal degeneration and supports its use in the study of neurorestorative therapies for Parkinson’s disease. Feb ’00 – Dec ’04 PhD project: “Development and maintenance of mesencephalic dopaminergic neurons: role of the Engrailed and Pbx1 transcription factors”. Aim of the project was to study the role of the Engrailed transcription factors in the development and maintenance of mesencephalic DA neurons and their interaction with their homeobox Pbx1 cofactor. Supervisor: Dr. H.H. Simon, Interdisciplinary Centre for Neuroscience, Department of Neuroanatomy III, University of Heidelberg, Germany. Apr ’96 – Apr ’99 Master Thesis: “In vivo PC3 overexpression by retroviral vector affects cell differentiation of rat cortical precursors.” The project aimed at investigating the functional role of the anti-proliferative gene PC3 (Tis21, Btg2) during development of the cerebral cortex, using in utero injection of replication incompetent retroviral vectors. Supervisor: Dr. F. Cremisi, Scuola Normale Superiore, Pisa. |
|
Appartenenza a società e comitati scientifici |
|
Societies memberships Member of the Italian Neuroscience Society (SINS) Member of the Federation of the European Neuroscience Societies (FENS) Reviewing committees Peer-review Journals Neuroscience Epilepsy Research Research in Developmental Disabilities International Journal of Molecular Sciences Biochemical Science Archives Italiennes de Biologie Expert Panel Member Expert Scientific Review Wellcome Trust |
|
Premi e riconoscimenti |
|
Apr ’17 Invited Speaker – “Wiring the Brain” Cold Spring Harbor Laboratory meeting. Jul ’10 Marie Curie COFUND “People” Research Fellowship. Oct ’09 Invited Speaker – XIII Italian Neuroscience Society National Congress, Milan, Italy. Feb ’09 Invited Speaker – LIMPE Seminars: “Old and new dopamine agonists in Parkinson's disease: a reappraisal”. Jan ’09 Invited Speaker – Italian League for Eliplepsy Meeting, Genetic Board, Rome, Italy. Sep ’07 Invited Speaker – LIMPE Seminars: “Experimental models of Parkinson’s disease” 25th Sept 2006 Dr. Rer. Nat. “magna cum laude” – University of Heidelberg, Germany. Nov ’06 Invited Speaker – Best Oral presentation – XXXIII LIMPE Annual Meeting, Stresa, Italy Sept ’03 Invited Speaker – X Italian Neuroscience Society National Congress, Pisa, Italy |
|
Convegni e conferenze |
|
|
|
Allegati |
|