TONGIORGI Enrico


Responsabile dell'U.O.

Cognome e Nome

TONGIORGI Enrico

Qualifica

PO

Dipartimento

Scienze della Vita

Settore scientifico disciplinare

Anatomia Comparata e Citologia BIO/06

E-mail

tongi@units.it

Telefono

Personale strutturato

Cognome e Nome

BAJ Gabriele

Qualifica

PA

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

FLORIAN Fiorella

Qualifica

Ricercatore

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

CESCA Fabrizia

Qualifica

RTDB

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

CINGOLANI Lorenzo

Qualifica

PA

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Personale non strutturato

Cognome e Nome

ROGGERO Ottavia

Qualifica

Assegnista

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

BIMBI Giorgia

Qualifica

Ph.D student

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

Agnès Thalhammer

Qualifica

RTDA

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

CIRACI Viviana

Qualifica

Assegnista

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

Fanny Jaudon

Qualifica

Assegnista

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

Jessica Muià

Qualifica

Assegnista

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

Lucia Celora

Qualifica

Ph.D student

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

Riccardo Ruggeri

Qualifica

Ph.D student

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Cognome e Nome

Krawczun-Rygmaczewska Alicja

Qualifica

Ph.D student

Dipartimento

Scienze della Vita

Ente di appartenenza

Università di Trieste

Linee di ricerca

1.  The “spatial and quantitative code model” of BDNF splice variants The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) is a key morphoregulatory molecule in neuronal development and plasticity. Transcription of the bdnf gene leads to 34 transcripts in humans and 22 in rodents, each with the same coding region (CDS), one out of 11 different 5’UTRs, and either a short or a long 3’UTR. To explain the biological role of these multiple BDNF splice variants we proposed the “spatial and quantitative code” model. This model is based on our finding that BDNF mRNA variants become spatially segregated in response to neuronal activation within three distinct subcellular domains: the soma (exons 1, 3, 5, 7, 8, 9a), the proximal (exon 4) or the distal (exon 2, 6) dendrites. We also showed that each mRNA variant has a different translatability and produces different quantity of BDNF in response to different neurotransmitters. Current research is focused on understanding the mechanisms of BDNF mRNA variants segregation and local translation and exploitation of the BDNF code to rescue dendritic atrophy in various neurological diseases. Translational Outcomes: 1) Patented high throughput cell-based assay to screen for natural extracts, nutraceutical and synthetic compounds able to modulate BDNF protein translation (PCT/EP2010/067081). 2) BDNF spatial code database in human and rodent brain for rational design of strategies to rescue neuronal atrophy and cognitive impairment in different brain areas.  2.  Pharmacological rescue of neuronal atrophy in Rett Syndrome Brain weight loss, shrinkage of the cortex with reduced soma and dendritic arborization in absence of neurodegenerative processes is a typical feature of the neurodevelopmental disorder Rett syndrome, an X-linked genetic disease mainly caused by mutations in the MeCP2 (Methyl-CpG binding protein-2) gene. Current major hypotheses for the causes of neuronal atrophy involve intrinsic (cell-autonomous) and extrinsic (non-cell autonomous) factors including impaired neurotrophic support due to reduced BDNF, decreased monoamine neurotransmission, increased oxidative stress and impaired neuron-glia crosstalk. Accordingly, we are testing the antidepressant Mirtazapine and other drugs to enhance monoamines and neurotrophic factors, reduce oxidative stress and rescue neuronal atrophy. The project is taking advantage of in vivo and in vitro models using a MeCP2 knock-out mouse and iPSCs-derived neuronal cultures produced from patient fibroblasts. Translational Outcomes: 1) Highly standardized mouse or rat cell-based model of neural development in vitro suitable for drug screening by high- content imaging analysis (Baj, Patrizio et al. Frontiers in Cellular Neuroscience, 2014). 2) Test of FDA/EMEA approved drugs in MeCP2 knock-out mouse in vivo and in vitro models to speed up translation towards clinical trials (repositioning approach). 3. Neurotrophic factors and cytokines as biomarkers of neuronal atrophy and its recovery Research activities are focused on the analysis of neurotrophic factors (particularly BDNF) and cytokines in serum and CSF to monitor pharmacological treatments and neuro-rehabilitative therapies in patients with neuronal atrophy associated with injury, neuropsychiatric or neurodegenerative diseases. Translational Outcomes: 1) Development and validation of innovative in vitro assays for clinical biomarkers of neurological and neuropsychiatric disorders and monitoring of pharmacological treatments or rehabilitative therapies. 2) The laboratory has collaborated with various private companies as beta-tester of pre-commercial kits.

Tecnologie in uso dall'UO

  1. 1.
    Primary neuronal cell cultures
  2. 2.
    Neuronal cell cultures derived from reprogrammed Murine Embryonic Stem Cells
  3. 3.
    Medium-scale automated High-Content Imaging analysis for phenotypic drug screening
  4. 4.
    Medium-scale automated neuronal cell survival assay
  5. 5.
    Medium-scale luciferase bioluminescent assay
  6. 6.
    Recombinant proteins production
  7. 7.
    Confocal microscopy
  8. 8.
    Structured Imaging Microscopy (SIM) superresolution analysis
  9. 9.
    Video-time lapse in vivo analysis of neuronal cultures
  10. 10.
    Biochemical assays (i.e., western blots, immunoprecipitation)
  11. 11.
    Molecular cloning
  12. 12.
    Time-lapse live imaging
  13. 13.
    Multi electrode array recordings
  14. 14.
    Brain slice patch-clamp electrophysiology
  15. 15.
    Optogenetics
  16. 16.
    Live ratiometric Ca2+ imaging

Strumentazione

Denominazione

Nikon CS-Si Spectral Confocal microscope with NIS Elements software suite
Nikon E800 light microscope with Nikon 1200 CCD camera
Nikon LE300 inverted light microscope with micromanipulators and chamber for live cell analysis
Nikon Cell analyzer (motorized fluorescence Ti-E microscope, CO2 incubator, 16 GBit camera, software for high content imaging analysis and time lapse)
Fully equipped Brain slice patch-clamp/optogentics set up
BioCAM X high resolution MEA set up
Nikon inverted microscope Axiovert200 equipped with Cool-LED technology and a ORCA-Flash4.0 V3 videocamera (Hamamatsu Photonics) for ratiometric Ca2+ imaging

Struttura ove la strumentazione è allocata

Dip. Scienze della Vita
Dip. Scienze della Vita
Dip. Scienze della Vita
Dip. Scienze della Vita
Dip. Scienze della Vita
Dip. Scienze della Vita
Dip. Scienze della Vita

Responsabile

E. Tongiorgi
E. Tongiorgi
E. Tongiorgi
E. Tongiorgi
L. Cingolani
L. Cingolani
F. Cesca

Pubblicazioni

  1. 1.
    Polacchini A, Girardi D, Falco A, Zanotta N, Comar M, De Carlo NA, Tongiorgi E. (2018). Distinct CCL2, CCL5, CCL11, CCL27, IL-17, IL-6, BDNF serum profiles correlate to different job-stress outcomes. Neurobiol Stress. Feb 16;8:82-91.
  2. 2.
    Donegà S., Tongiorgi E. (2018) Detecting BDNF Protein Forms by ELISA, Western Blot, and Immunofluorescence. In: Duarte C., Tongiorgi E. (eds) Brain-Derived Neurotrophic Factor (BDNF). Neuromethods, vol 143. Humana, New York, NY
  3. 3.
    Nerli E, Roggero OM, Baj G, Tongiorgi E. (2020) In vitro modeling of dendritic atrophy in Rett syndrome: determinants for phenotypic drug screening in neurodevelopmental disorders. Sci Rep. Feb 11 10:2491
  4. 4.
    Flores Gutiérrez J, De Felice C, Natali G, Leoncini S, Signorini C, Hayek J, Tongiorgi E (2020). Protective role of mirtazapine in adult female Mecp2+/- mice and patients with Rett syndrome. . J Neurodev Disord. Sep 28;12(1):26.
  5. 5.
    Fabbretti E, Antognolli G, Tongiorgi E. (2021) Amyloid-β Impairs Dendritic Trafficking of Golgi-Like Organelles in the Early Phase Preceding Neurite Atrophy: Rescue by Mirtazapine. Front Mol Neurosci. Jun 3;14:661728.
  6. 6.
    Ferrante D, Sterlini B, Prestigio C, Marte A, Corradi A, Onofri F, Tortarolo G, Vicidomini G, Petretto A, Muia J, Thalhammer A, Valente P, Cingolani LA, Benfenati F, Baldelli P (2021) PRRT2 modulates presynaptic Ca(2+) influx by interacting with P/Q-type channels. Cell Rep 35: 109248
  7. 7.
    Scaramuzza L, De Rocco G, Desiato G, Cobolli Gigli C, Chiacchiaretta M, Mirabella F, Pozzi D, De Simone M, Conforti P, Pagani M, Benfenati F, Cesca F, Bedogni F, Landsberger N. The enhancement of activity rescues the establishment of Mecp2 null neuronal phenotypes. EMBO Mol Med. 2021 Apr 9;13(4):e12433. doi: 10.15252/emmm.202012433.
  8. 8.
    Buffolo F, Petrosino V, Albini M, Moschetta M, Carlini F, Floss T, Kerlero de Rosbo N, Cesca F, Rocchi A, Uccelli A, Benfenati F. Neuroinflammation induces synaptic scaling through IL-1β-mediated activation of the transcriptional repressor REST/NRSF. Cell Death Dis 2021 Feb 15;12(2):180. doi: 10.1038/s41419-021-03465-6
  9. 9.
    Carminati E, Buffolo F, Rocchi A, Michetti C, Cesca F* and Benfenati F*. Mild inactivation of RE-1 Silencing Transcription Factor (REST) reduces susceptibility to kainic acid-induced seizures. Frontiers in Cell Neurosci 2020 Jan 10;13:580. doi: 10.3389/fncel.2019.00580 *corresponding authors
  10. 10.
    Jaudon F, Chiacchiaretta M, Albini M, Ferroni S, Benfenati F and Cesca F. Kidins220/ARMS controls astrocyte calcium signaling and neuron-astrocyte communication. Cell Death Differ. 2019 Oct 17. doi: 10.1038/s41418-019-0431-5
  11. 11.
    Chiacchiaretta M, Bramini M, Rocchi A, Armirotti A, Giordano E, Vázquez E, Bandiera T, Ferroni S, Cesca F*, Benfenati F*. Graphene oxide upregulates the homeostatic functions of primary astrocytes and modulates astrocyte-to-neuron communication. Nano Lett. 2018 Aug 8. doi: 10.1021/acs.nanolett.8b02487 *equal contribution
  12. 12.
    Sacco, P., Baj, G., Asaro, F., Marsich, E., Donati, I.Substrate Dissipation Energy Regulates Cell Adhesion and Spreading(2020) Advanced Functional Materials, 30 (31). DOI: 10.1002/adfm.202001977
  13. 13.
    Martinelli, V., Bosi, S., Penã, B., Baj, G., Long, C.S., Sbaizero, O., Giacca, M., Prato, M., Mestroni, L.3D Carbon-Nanotube-Based Composites for Cardiac Tissue Engineering(2018) ACS Applied Bio Materials, 1 (5), pp. 1530-1537. Doi: 10.1021/acsabm.8b00440
  14. 14.
    Singer, W., Manthey, M., Panford-Walsh, R., Matt, L., Geisler, H.-S., Passeri, E., Baj, G., Tongiorgi, E., Leal, G., Duarte, C.B., Salazar, I.L., Eckert, P., Rohbock, K., Hu, J., Strotmann, J., Ruth, P., Zimmermann, U., Rüttiger, L., Ott, T., Schimmang, T., Knipper, M. BDNF-Live-Exon-Visualization (BLEV) Allows Differential Detection of BDNF Transcripts in vitro and in vivo. (2018) Frontiers in Molecular Neuroscience, 11, art. no. 325, . DOI: 10.3389/fnmol.2018.00325
  15. 15.
    Girardelli, M., Loganes, C., Pin, A., Stacul, E., Decleva, E., Vozzi, D., Baj, G., De Giacomo, C., Tommasini, A., Bianco, A.M. Novel NOD2 Mutation in Early-Onset Inflammatory Bowel Phenotype. Inflammatory Bowel Diseases 2018 24 (6) 1204-12. doi: 10.1093/ibd/izy061.

Dottorati di ricerca

Componente UO

E. Tongiorgi
F. Cesca
L. Cingolani

Dottorato di ricerca

Biomedicina Molecolare
Biomedicina Molecolare
Biomedicina Molecolare

Coordinatore

G.Meroni
G.Meroni
G.Meroni

Sede

Dip. Scienze della Vita
Dip. Scienze della Vita
Dip. Scienze della Vita