Dott. Giuseppe Chiantia
- NEUROSCIENZE
- Phd: 37th cycle
- Matriculation number: 768283
Phd thesis
Title of research project:
Synaptic bases of aberrant somatosensory encoding in CDKL5 deficiency disorder: characterization of morphological, biophysical and electrophysiological alterations induced by loss of CDKL5
Mutations in the X-linked serine/threonine kinase cyclin-dependent kinase-5 (CDKL5) gene are responsible for a severeneurodevelopmental disorder, CDKL5 deficiency disorder (CDD). CDD is characterized by deficits of motor and language abilities,stereotyped repetitive hand movements, muscle hypotonia, autonomic dysfunctions, severe cognitive impairments and autistic traits.Moreover, CDD patients exhibit sensory alterations such as cortical visual impairment, altered tactile sensitivity and increased sensitivity to vibrations and thermal pain1. Interestingly, adult Cdkl5 knock-out mice show analogous sensory alteration such as visual, auditory, somatosensory and tactile impairment. The importance of CDKL5 is demonstrated by the fact that its loss results in severe alterations of synaptic transmission and plasticity. CDKL5 is localized in the post-synaptic compartment of excitatory synapses where it interacts with key excitatory postsynaptic proteins. In Cdkl5 knock-out mice dendritic arborization is less complex and dendritic spines density and morphology are altered, suggesting that CDKL5 is important in regulating excitatory connectivity. In addition, these morphological abnormalities are associated to functional alterations such as impaired long-term potentiation (LTP). In a recent work from our laboratory, it has been demonstrated that the activity of excitatory neuron is reduced, in particular, we found a reduced frequency of miniature excitatory postsynaptic current and NMDA receptors signaling. In contrast to excitation, the role of CDKL5 in regulating inhibitory synaptic properties remain almost unexplored. Recently, it has been demonstrated that a selective deletion of the Cdkl5 gene in interneurons produced abnormal alterations in terms of locomotor activity, sociability and repetitive behavior. Mice with selective deletion of CDKL5 from forebrain neurons display altered parameters of miniature inhibitory currents (mIPSCs), a defect that is compatible with an aberrant composition of postsynaptic GABAA receptors, and presynaptic inhibitory inputs. However, underlying mechanisms which cause the functional alterations in GABAergic connectivity related with CDKL5 deficiency are still largely unknown. As a consequence of these synaptic alterations, an imbalance between excitatory and inhibitory synaptic balance (E/I balance) in CDKL5-deficient neurons can be hypothesized. The purpose of my thesis is to characterize electrophysiological properties of GABAergic interneurons, to assess the role of Cdkl5 in inhibitory synaptic transmission through immunofluorescence and electrophysiological techniques.
Research activities
"How we reason" - M. Bucciarelli - Toolbox Course, 22nd and 25th May 2022
"From neural cell excitability to brain circuit recording, visualization and manipulation" - F. Tempia, F. Ferrini, G. Concina, S. Zucca, S. Bovetti - Toolbox Course, 1stFebruary and 8th, 15th, 22nd, 29th March 2022
"Introduction to research methodology" - D. Romano - Toolbox Course, 4th, 11th, 18th and 25th February 2022
"Clinical, methodological and theoretical aspects of translational and cognitive neuroscience" - A. Berti, A. Chiò, M. Giustetto - Toolbox Course, 20th January 2022
"Brain stimulation for neurological diseases" - L. Lopiano, M. Bozzali, M. G. Rizzone - Toolbox Course, 17th March and 7th April 2022
"In vitro and ex vivo approaches to study rodent and human neural cells" - A. Buffo, E. Boda - Toolbox Course, 28th June and 4th July
"Corso obbligatorio di formazione in materia di salute e sicurezza nei luoghi di lavoro", e-learning course
"Welcome and Informative Meeting for 1st year students" - A. Calvo - Meeting, 17th December 2021
"Workshop: Public engagement and outreach" - Prof.ssa Annalisa Buffo- 18th and 19th november 2022
"Synaptic mechanisms of pattern completion in the hippocampal CA3 region" Prof. Peter Jonas | Institute of Science and Technology Austria, ISTA
“Optical analysis of neuronal ionic currents in acute brain slices” Dott. Marco Canepari 26th June
«Role of phytocannabinoids in neuroinflammation and Nanotechnological approach for topical-dermal delivery and intranasal-direct brain targeting» Prof. Shimon Ben-Shabat Tuesday, June 13 2023
"Electrified brains: from the torpedo fish to transcranial direct current stimulation" Marco Cambiaghi 6/6/23
“Choroid plexus: a new entry point to study the brain development” Dott. Annarita Patrizi 30th May, 2023
“Harnessing the heterogeneity of neuroinflammatory responses to tackle neurodegeneration in Amyotrophic Lateral" Prof. Marco Peviani 28/04/23
Sclerosis”
2019
Calorio, E. Hidisoglou, D. Gavello, G. Chiantia, C. Salio, M, Sassoè-Pognetto, P. Defilippi, F. Balzac, E. Turco, G. C. L. Bett, R. L. Rasmusson, A. Marcantoni, E. Carbone. Altered L-type channel gating, action potential firing and inhibitory synaptic responses in hippocampal neurons of the autistic Timothy syndrome type-2 mouse. XX Scientific Convention Telethon
2020
Antonia Gurgone, Riccardo Pizzo, Alessandra Raspanti, Giuseppe Chiantia, Andrea Marcantoni and Maurizio Giustetto. Synaptic and behavioural impairments shown by cdkl5-ko mice can be rescued by positive allosteric modulation of metabotropic glutamate receptors. Cdkl5 forum 2020
Enis Hidisoglu, Giuseppe Chiantia, Claudio Franchino, Andrea Marcantoni, Emilio Carbone. “Early alterations of hippocampal gabaergic synaptic properties induced by Aβ42 oligomers” Alzheimer & Dementia. 07 December 2020 https://doi.org/10.1002/alz.043482
2021
Gurgone A, Pizzo R, Raspanti A., Chiantia G., Lupori L., Marcantoni A, Pizzorusso T., and Giustetto M. “CDKL5-Shank1 interaction discloses mGluR5 as a promising molecular target for CDKL5 deficiency disorder therapy.” SfN Global Connectome January 11th-13th 2021
2022
A Marcantoni, G Chiantia, G Tomagra, E Hidisoglu, V Carabelli, E Carbone. “ MEA recordings of spontaneously firing rat chromaffin cells uncover new high-frequency long-lasting bursts and well-resolved AP-driven Na+, K+ and Ca2+ currents sustaining the firing” 4th European Calcium Channels Conference- Alpbach, Austria- 24-28 May 2022
Giuseppe Chiantia, Andrea Marcantoni, Maurizio Giustetto. “Sub-toxic doses of glyphosate cause synaptic alterations of inhibitory transmission” National meeting of phd students in Neuroscience. SINS. Brescia June 11th, 2022
Lisa Pavinato, Jennifer Stanic, Marta Barzasi, Ivano Eberini, Monica Diluca, Antonia Gurgone, Giuseppe Chiantia, Andrea Marcantoni, Elisa Biamino, Marco Spada, Susan M. Hiatt, Valentina Cipriani, Letizia Vestito, Damian Smedley, Genomics England Research Consortium, Alessandro Bruselles, Silvia De Rubeis, Joseph D. Buxbaum, Marco Tartaglia, Maurizio Giustetto, Fabrizio Gardoni, Alfredo Brusco. “Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder”. Society of Human Genetics (SIGU) conference 2022
2023
Marta Barzasi, Lisa Pavinato, Jennifer Stanic, Antonia Gurgone, Giuseppe Chiantia, Valentina Cipriani, Ivano Eberini, Luca Palazzolo, Monica Di Luca, Alex Costa, Andrea Marcantoni, Elisa Biamino, Marco Spada, Susan M. Hiatt, Whitley V. Kelley, Letizia Vestito, Sanjay M. Sisodiya, Genomics England Research Consortium, Stephanie Efhtymiou, Prem Chand, Alessandro Bruselles, Simona Cardaropoli, Marco Tartaglia, Silvia De Rubeis, Joseph D. Buxbaum, Damian Smedley, Giovanni Battista Ferrero, Maurizio Giustetto, Fabrizio Gardoni, Alfredo Brusco .“Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder”. SINS September 2023
Andrea Marcantoni, Maurizio Giustetto, Maria Sabina Cerullo, Pol Buxeda, Giulia Tomagra, Giuseppe Chiantia, Valentina Carabelli and Emilio Carbone. Amyloid Beta42 oligomers up-regulate the excitatory synapses by potentiating presynaptic release while impairing postsynaptic NMDA receptors. J Physiol. 2020; doi: 10.1113/JP279345
Andrea Marcantoni, Chiara Calorio, Enis Hidisoglu, Giuseppe Chiantia, Emilio Carbone 2 channelopathies causing autism: new hallmarks on Timothy syndrome. Pflügers Archiv - European Journal of Physiology 2020 https://doi.org/10.1007/s00424-020-02430-0
A Gurgone, R Pizzo, A Raspanti, G Chiantia, S Devi, N Morello, F Pilotto, S Gnavi, L Lupori, R Mazziotti, G Sagona, E Putignano, A Nocentini, C T Supuran, A Marcantoni, T Pizzorusso, M Giustetto. “mGluR5 PAMs rescue cortical and behavioural defects in a mouse model of CDKL5 deficiency disorder”. Neuropsychopharmacology (2022) https:// doi.org/10.1038/s41386-022-01412-3
Andrea Marcantoni, Giuseppe Chiantia, Giulia Tomagra, Enis Hidisoglu, Claudio Franchino, Valentina Carabelli, Emilio Carbone. “Two firing modes and well‐resolved Na+, K+, and Ca2+ currents at the cell‐microelectrode junction of spontaneously active rat chromaffin cell on MEAs”. Pflügers Archiv - European Journal of Physiology (2022). https://doi.org/10.1007/s00424-022-02761-0
Carla Liaci, Mattia Camera, Valentina Zamboni, Gabriella Sarò, Alessandra Ammoni, Elena Parmigiani, Luisa Ponzoni, Enis Hidisoglu, Giuseppe Chiantia, Andrea Marcantoni, Maurizio Giustetto, Giulia Tomagra, Valentina Carabelli, Federico Torelli, Mariaelvina Sala, Yuchio Yanagawa, Kunihiko Obata, Emilio Hirsch, Giorgio R Merlo. “Loss of ARHGAP15 affects the directional control of migrating interneurons in the embryonic cortex and increases susceptibility to epilepsy” Front Cell Dev Biol 2022 Dec 8;10:875468.doi: 10.3389/fcell.2022.875468 eCollection 2022.
Hidisoglu*, Giuseppe Chiantia*, Claudio Franchino, G.Tomagra, M. Giustetto, E. Carbone, V.Carabelli, A. Marcantoni. “The RyR-calstabin interaction stabilizer S107 protects hippocampal neurons from GABAergic synaptic alterations induced by Abeta42 oligomers”. 2022 Dec;600(24):5295-5309. doi: 10.1113/JP283537. Epub 2022 Nov 15 *Equally contributing authors
Giuseppe Chiantia, Enis Hidisoglu and Andrea Marcantoni. “The role of ryanodine receptors in regulating neuronal activity and its connection to the development of Alzheimer's disease” Cells 2023. doi: 10.3390/cells12091236.
Lisa Pavinato, Jennifer Stanic, Marta Barzasi, Antonia Gurgone, Giuseppe Chiantia, Valentina Cipriani, Ivano Eberini, Luca Palazzolo, Monica Diluca, Alex Costa, Andrea Marcantoni, Elisa Biamino, Marco Spada, Susan M. Hiatt, Whitley V. Kelley, Letizia Vestito, Sanjay M. Sisodiya, Genomics England Research Consortium, Alessandro Bruselles, Simona Cardaropoli, Marco Tartaglia, Silvia De Rubeis, Joseph D. Buxbaum, Damian Smedley, Giovanni Battista Ferrero, Maurizio Giustetto, Fabrizio Gardoni, Alfredo Brusco. “Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder”. Genetics in Medicine 2023 2023 Jul 1;100922. doi: 10.1016/j.gim.2023.100922.
Enis Hidisoglu & Giuseppe Chiantia .”Frontal EEG alterations induced by hippocampal amyloid pathology in rats “ Advances in Medical Sciences.
2022
Poster at SINS National Meeting of PhD Students in Neuroscience. June 11th, Brescia (Italy).
Symposium "Mechanisms, Therapies and Biomarkers in Neurodevelopmental Disorders". Scuola Normale Superiore of Pisa (Italy), May 21st 2022.
2022
"NICO NeuroWebinar" - Virtual conferences
Winner of "1st Prize Enrica Marzola" 2022
Best poster BraYn 2023