Direzione e uffici C.I.B.

Direzione CIB:
Prof. Claudio Schneider
Email: claudio.schneider@Lncib.it

Segreteria CIB:
Prof. Roberto Gambari
Email: roberto.gambari@unife.it

SEGRETERIA ORGANIZZATIVA:
Elisabetta Lambertini
Tel: 0532/974451
Fax: 0532/974484
E-mail: lmblbt@unife.it

AMMINISTRAZIONE:
Vanessa Florit
Area di Ricerca
Padriciano, 99 - 34012 Trieste
Tel: 040/398979
Fax: 040/398990
E-mail: cib@lncib.it

Posta certificata C.I.B.:
cib@poste-certificate.it

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Tongiorgi Enrico Stampa
RESPONSABILE DELLA U. O.

Cognome e Nome Tongiorgi Enrico
Qualifica
Professore Ordinario
Dipartimento Scienze della Vita
Settore Scientifico Disciplinare Anatomia Comparata e Citologia BIO/06
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PERSONALE STRUTTURATO

Cognome e Nome BAJ Gabriele
Qualifica
RTD-b Anatomia Comparata e Citologia BIO/06
Dipartimento
Scienze della Vita
Ente di appartenenza Università di Trieste
Cognome e Nome FLORIAN Fiorella
Qualifica
RU Anatomia Comparata e Citologia BIO/06
Dipartimento
Scienze della Vita
Ente di appartenenza Università di Trieste

PERSONALE NON STRUTTURATO

Cognome e Nome ROGGERO Ottavia
Qualifica Assegnista di Ricerca
Dipartimento Scienze della Vita
Ente di appartenenza
Università di Trieste

Cognome e Nome BIMBI Giorgia
Qualifica Dottoranda
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 POSSESSO DELL'U. O.

  • Primary neuronal cell cultures
  • Neuronal cell cultures derived from reprogrammed Murine Embryonic Stem Cells
  • Medium-scale automated  High-Content Imaging analysis for phenotypic drug screening
  • Medium-scale automated  neuronal cell survival assay
  • Medium-scale luciferase bioluminescent assay
  • Recombinant proteins production
  • Confocal microscopy
  • Structured Imaging  Microscopy (SIM) superresolution analysis
  • Video-time lapse in vivo analysis of neuronal cultures

STRUMENTAZIONE

Denominazione
Struttura ove la strumentazione è allocata
Responsabile della strumentazione
Nikon CS-Si Spectral Confocal microscope with NIS Elements software suite
Dip. Scienze della Vita – Light Microcospy Imaging Center (LMIC)
E. Tongiorgi
Nikon E800 light microscope with Nikon 1200 CCD camera
Dip. Scienze della Vita – Light Microcospy Imaging Center (LMIC)
E. Tongiorgi
Nikon LE300 inverted light microscope with micromanipulators and chamber for live cell analysis
Dip. Scienze della Vita – Light Microcospy Imaging Center (LMIC)
E. Tongiorgi
Nikon Cell analyzer (motorized fluorescence Ti-E microscope, CO2 incubator, 16 GBit camera, software for high content imaging analysis and time lapse)
Dip. Scienze della Vita – Light Microcospy Imaging Center (LMIC)
E. Tongiorgi

PUBBLICAZIONI

Carlino D, Francavilla R, Baj G, Kulak K, d'Adamo P, Ulivi S, Cappellani S, Gasparini P, Tongiorgi E. (2015). Brain-derived neurotrophic factor serum levels in genetically isolated populations: gender-specific association with anxiety disorder subtypes but not with anxiety levels or Val66Met polymorphism. PeerJ. Oct 29 3:e1252.

Vicario A, Colliva A, Ratti A, Davidovic L, Baj G, Gricman Ł, Colombrita C, Pallavicini A, Jones KR, Bardoni B, Tongiorgi E. (2015). Dendritic targeting of short and long 3' UTR BDNF mRNA is regulated by BDNF or NT-3 and distinct sets of RNA-binding proteins. Front Mol Neurosci. Oct 29;8:62

Polacchini A, Metelli G, Francavilla R, Baj G, Florean M, Mascaretti LG, Tongiorgi E. (2015). A method for reproducible measurements of serum BDNF: comparison of the performance of six commercial assays. Sci Rep. Dec 10 5:17989

Girardi D, Falco A, De Carlo A, Benevene P, Comar M, Tongiorgi E, Bartolucci GB. (2016). Authors' response. J Behav Med. Apr 39(2):367-8.

Bittolo T, Raminelli CA, Deiana C, Baj G, Vaghi V, Ferrazzo S, Bernareggi A, Tongiorgi E. (2016). Pharmacological treatment with mirtazapine rescues cortical atrophy and respiratory deficits in MeCP2 null mice. Sci Rep. Jan 25 6:19796.

Polacchini A, Albani C, Baj G, Colliva A, Carpinelli P, Tongiorgi E. (2016) Combined cisplatin and aurora inhibitor treatment increase neuroblastoma cell death but surviving cells overproduce BDNF. Biol Open. Jul 15;5(7):899-907.

Baj G, Pinhero V, Vaghi V, Tongiorgi E. (2016) Signaling pathways controlling activity-dependent local translation of BDNF and their localization in dendritic arbors. J Cell Sci. Jul 15;129(14):2852-64.

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.

Singer W, Manthey M, Panford-Walsh R, Matt L, Geisler HS, Passeri E, Baj G, Tongiorgi E, Leal G, Duarte CB, Salazar IL, Eckert P, Rohbock K, Hu J, Strotmann J, Ruth P, Zimmermann U, Rüttiger L, Ott T, Schimmang T, Knipper M. (2018). BDNF-Live-Exon-Visualization (BLEV) Allows Differential Detection of BDNF Transcripts in vitro and in vivo. Front Mol Neurosci. Sep 27;11:325.

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

Colliva A., Maynard K.R., Martinowich K., Tongiorgi E. (2018) Detecting Single and Multiple BDNF Transcripts by In Situ Hybridization in Neuronal Cultures and Brain Sections. In: Duarte C., Tongiorgi E. (eds) Brain-Derived Neurotrophic Factor (BDNF). Neuromethods, vol 143. Humana, New York, NY

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


DOTTORATI DI RICERCA

Componente U.O. Dottorato di Ricerca Coordinatore Sede
E. Tongiorgi
Scuola di Dottorato in Neuroscienze e Scienze Cognitive
P.P. Battaglini
Dip. Scienze della Vita
P.Edomi
Scuola di Dottorato in Neuroscienze e Scienze Cognitive
P.P. Battaglini
Dip. Scienze della Vita
R. Marzari
Dottorato in Nanotecnologie
P.Tommasini
Dip. Fisica
F. Florian
Dottorato in Nanotecnologie
P.Tommasini
Dip. Fisica

CONGRESSI C.I.B.

Congressi Partecipazione
CNB4

CNB5

CNB6
Si
CNB7
Si
CNB8

CNB9
CNB10