ROBERTA CELLI

PhD Graduate

PhD program:: XXXII



Thesis title: IDENTIFICATION OF NEW MOLECULAR TARGETS FOR THE EXPERIMENTAL TREATMENT OF ABSENCE EPILEPSY

The epilepsies represent a heterogeneous group of disorders with different electrographic, etiologies, behavioural and seizure pattern which largely influence the quality of life of patients. Childhood absence epilepsy (CAE) accounts for 2% to 8% of patients with epilepsy and generally occurs at 4-12 years of age. CAE consists in a sudden start and termination of activity with loss of awareness for a number of seconds resulting in a blank stare, and sometimes accompanied by flickering of the eyelids and mouth movements. Recent studies showed that 30% of children with absence epilepsy fail to achieve seizure control and 60% are affected by severe neuropsychiatric comorbid conditions, in particular cognitive deficits and long-term psychosocial difficulties. Drugs currently used for the treatment of absence epilepsy include the T-type calcium channel blocker ethosuximide, and valproic acid, lamotrigine and clonazepam. All these drugs can be effective, but their use is limited by class-related adverse effects, such as sedation, dizziness, and cerebellar motor symptoms. For this reason, new anti-absence drugs are badly needed. The experiments described in this thesis aim to investigate new molecular targets for the experimental treatment of absence epilepsy. It has been suggested that the α2δ subunit of high voltage-activated VSCCs may be associated with T-type channels, whose activation contributes to the pathological oscillatory activity of the cortico-thalamo-cortical network. Considering that this subunit is also targeted by thrombospondins, which regulate synaptogenesis in the CNS, and it’s implicated in the process of epileptogenesis, the axis thrombospondins/2 may play a potential role in the pathophysiology of non-convulsive epilepsy that needs to be evaluated. Moreover, the role of the δ subunit contained in extrasynaptic GABAA receptors and thalamocortical tonic GABAA current in the development of absence seizures remains to be demonstrated; thus, an appropriate mouse model has been adopted. The melatoninergic system in absence seizures has been examined in WAG/Rij rats, also exploring whether melatonin could have an impact on the comorbid depression typical in these rats. Pharmacological studies have been carried out to establish whether positive allosteric modulators of mGlu5 receptors could be developed as putative anti-absence drugs, especially for patients who are refractory to conventional treatment.

Research products

11573/1707218 - 2023 - Noradrenaline and Seizures: A Perspective on the Role of Adrenergic Receptors in Limbic Seizures
Biagioni, Francesca; Celli, Roberta; Puglisi-Allegra, Stefano; Nicoletti, Ferdinando; Giorgi, Filippo Sean; Fornai, Francesco - 01a Articolo in rivista
paper: CURRENT NEUROPHARMACOLOGY (Hilversum: Bentham Science Publishers) pp. 2233-2236 - issn: 1875-6190 - wos: WOS:001075342800007 (3) - scopus: 2-s2.0-85135814176 (3)

11573/1671811 - 2023 - mGlu3 metabotropic glutamate receptors as a target for the treatment of absence epilepsy. Preclinical and human genetics data
Celli, R.; Striano, P.; Citraro, R.; Di Menna, L.; Cannella, M.; Imbriglio, T.; Koko, M.; De Sarro, G.; Monn, J. A.; Battaglia, G.; Van Luijtelaar, G.; Nicoletti, F.; Russo, E.; Leo, A.; Palotie, A.; Folkhalsan, A. -E. L.; Ruppert, A. -K.; Lal, D.; Thiele, H.; Altmuller, J.; Jabbari, K.; Nurnberg, P.; Sander, T.; Siren, A.; Becker, F.; Lerche, H.; Weber, Y.; Koeleman, B.; Caglayan, H.; Hjalgrim, H.; Moller, R.; Muhle, H.; Helbig, I.; Everett, K.; May, P.; Krause, R.; Balling, R.; Nabbout, R.; Zara, F.; Scala, M.; Iacomino, M.; Scudieri, P.; Bocciardi, R.; Balagura, G.; Minetti, C.; Riva, A.; Vari, M. S.; Amadori, E.; Perinelli, M.; Verrotti, A.; Baulac, S.; Kunz, W. - 01a Articolo in rivista
paper: CURRENT NEUROPHARMACOLOGY (Hilversum: Bentham Science Publishers) pp. 105-118 - issn: 1875-6190 - wos: WOS:000936995500010 (3) - scopus: 2-s2.0-85141219831 (4)

11573/1694058 - 2023 - Blunted type-5 metabotropic glutamate receptor-mediated polyphosphoinositide hydrolysis in two mouse models of monogenic autism
Di Menna, Luisa; Orlando, Rosamaria; D'errico, Giovanna; Ginerete, Roxana Paula; Machaczka, Agata; Bonaccorso, Carmela Maria; Arena, Andrea; Spatuzza, Michela; Celli, Roberta; Alborghetti, Marika; Ciocca, Eleonora; Zuena, Anna Rita; Scioli, Mariarosaria; Bruno, Valeria; Battaglia, Giuseppe; Nicoletti, Ferdinando; Catania, Maria Vincenza - 01a Articolo in rivista
paper: NEUROPHARMACOLOGY ([Oxford] : Elsevier Ltd.) pp. 109642- - issn: 1873-7064 - wos: WOS:001037419700001 (2) - scopus: 2-s2.0-85164360323 (2)

11573/1498075 - 2021 - Targeting Ionotropic Glutamate Receptors In The Treatment Of Epilepsy
Celli, Roberta - 01a Articolo in rivista
paper: CURRENT NEUROPHARMACOLOGY (Hilversum: Bentham Science Publishers) pp. - - issn: 1570-159X - wos: WOS:000656531300004 (28) - scopus: 2-s2.0-85107133578 (27)

11573/1675203 - 2021 - Group I metabotropic glutamate receptor-mediated long term depression is disrupted in the hippocampus of WAG/Rij rats modelling absence epilepsy.
Di Cicco, Gabriele; Marzano, Emanuela; Iacovelli, Luisa; Celli, Roberta; Van Luijtelaar, Gilles; Nicoletti, Ferdinando; T Ngomba, Richard; J Wall, Mark - 01a Articolo in rivista
paper: NEUROPHARMACOLOGY ([Oxford] : Elsevier Ltd.) pp. 108686-108697 - issn: 1873-7064 - wos: WOS:000693528700001 (3) - scopus: 2-s2.0-85109201939 (3)

11573/1498053 - 2020 - Pharmacological activation of mGlu5 receptors with the positive allosteric modulator VU0360172, modulates thalamic GABAergic transmission
Celli, Roberta; Wall, Mark J.; Santolini, Ines; Vergassola, Matteo; Di Menna, Luisa; Mascio, Giada; Cannella, Milena; Van Luijtelaar, Gilles; Pittaluga, Anna; Ciruela, Francisco; Bruno, Valeria Maria Gloria; Nicoletti, Ferdinando; Ngomba, Richard T. - 01a Articolo in rivista
paper: NEUROPHARMACOLOGY (Elsevier Science Limited:Oxford Fulfillment Center, PO Box 800, Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000, 011 44 1865 843699, EMAIL: asianfo@elsevier.com, tcb@elsevier.co.UK, INTERNET: http://www.elsevier.com, http://www.elsevier.com/locate/shpsa/, Fax: 011 44 1865 843010) pp. - - issn: 0028-3908 - wos: WOS:000579490400003 (9) - scopus: 2-s2.0-85089702834 (9)

11573/1305073 - 2019 - Targeting metabotropic glutamate receptors in the treatment of epilepsy: rationale and current status
Celli, R.; Santolini, I.; Van Luijtelaar, G.; Ngomba, R. T.; Bruno, V.; Nicoletti, F. - 01g Articolo di rassegna (Review)
paper: EXPERT OPINION ON THERAPEUTIC TARGETS (--London United Kingdom:Informa Healthcare -London : Ashley, 2002-.) pp. 341-351 - issn: 1472-8222 - wos: WOS:000462246200007 (36) - scopus: 2-s2.0-85063198976 (37)

11573/1115309 - 2018 - Genetic rescue of absence seizures
Mccafferty, Cian; Connelly, William M; Celli, Roberta; Ngomba, Richard T; Nicoletti, Ferdinando; Crunelli, Vincenzo - 01a Articolo in rivista
paper: CNS NEUROSCIENCE & THERAPEUTICS (Oxford : Blackwell, 2008-) pp. 745-748 - issn: 1755-5930 - wos: WOS:000438716000011 (4) - scopus: 2-s2.0-85050007635 (4)

11573/1177276 - 2018 - Abnormal hippocampal melatoninergic system: a potential link between absence epilepsy and depression-like behavior in WAG/Rij rats?
Moyanova, Slavianka; De Fusco, Antonio; Santolini, Ines; Celli, Roberta; Bucci, Domenico; Mastroiacovo, Federica; Battaglia, Giuseppe; Nicoletti, Ferdinando; Tchekalarova, Jane - 01a Articolo in rivista
paper: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. - - issn: 1661-6596 - wos: WOS:000442807400152 (12) - scopus: 2-s2.0-85049829805 (12)

11573/960762 - 2017 - The Α2δ Subunit and Absence Epilepsy: Beyond Calcium Channels ?
Celli, Roberta; Santolini, Ines; Guiducci, Michela; Van Luijtelaar, Gilles; Parisi, Pasquale; Striano, Pasquale; Gradini, Roberto; Battaglia, Giuseppe; Ngomba, Richard T; Nicoletti, Ferdinando - 01a Articolo in rivista
paper: CURRENT NEUROPHARMACOLOGY (Hilversum: Bentham Science Publishers) pp. 918-925 - issn: 1570-159X - wos: WOS:000407196400009 (15) - scopus: 2-s2.0-85029037479 (17)

11573/1115049 - 2017 - Alterations in the α2δ ligand, thrombospondin-1, in a rat model of spontaneous absence epilepsy and in patients with idiopathic/genetic generalized epilepsies
Santolini, Ines; Celli, Roberta; Cannella, Milena; Imbriglio, Tiziana; Guiducci, Michela; Parisi, Pasquale; Schubert, Julian; Iacomino, Michele; Zara, Federico; Lerche, Holger; Moyanova, Slavianka; Ngomba, Richard Teke; Van Luijtelaar, Gilles; Battaglia, Giuseppe; Bruno, Valeria; Striano, Pasquale; Nicoletti, Ferdinando; Palotie, Aarno; Folkhälsan, Anna-Elina Lehesjoki; Ruppert, Ann-Kathrin; Siren, Auli; Koeleman, Bobby; Lal, Dennis; Becker, Felicitas; Caglayan, Hande; Hjalgrim, Helle; Muhle, Hiltrud; Thiele, Holger; Helbig, Ingo; Altmuller, Janine; Jabbari, Kamel; Everett, Kate; May, Patrick; Nurnberg, Peter; Møller, Rikke; Nabbout, Rima; Krause, Roland; Balling, Rudi; Baulac, Stephanie; Sander, Thomas; Kunz, Wolfram; Weber, Yvonne; Bianchi, Amedeo; La Neve, Angela; Coppola, Antonietta; Striano, Salvatore; Capovilla, Giuseppe; Ferlazzo, Edoardo; Bagnasco, Irene; Ferretti, Alessandro; Di Bonaventura, Carlo; Vari, Maria Stella; Pinto, Francesca; Bisulli, Francesca; Tinuper, Paolo; Minetti, Carlo; Belcastro, Vincenzo; Giordano, Lucio; Gambardella, Antonio - 01a Articolo in rivista
paper: EPILEPSIA (Hoboken: John Wiley & Sons Copenhagen: E. Munksgaard) pp. 1993-2001 - issn: 0013-9580 - wos: WOS:000414363000022 (9) - scopus: 2-s2.0-85029422978 (9)

11573/575820 - 2014 - Head-to head comparison of mGlu1 and mGlu5 receptor activation in chronic treatment of absence epilepsy in WAG/Rij rats.
D'amore, V.; Santolini, I.; Celli, R.; Lionetto, L.; De Fusco, A.; Simmaco, Maurizio; Van Rijn, C. M.; Vieira, E.; Stauffer, S. R.; Conn, P. J.; Bosco, P.; Nicoletti, Ferdinando; Van Luijtelaar, G.; Ngomba, R. T. - 01a Articolo in rivista
paper: NEUROPHARMACOLOGY (Elsevier Science Limited:Oxford Fulfillment Center, PO Box 800, Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000, 011 44 1865 843699, EMAIL: asianfo@elsevier.com, tcb@elsevier.co.UK, INTERNET: http://www.elsevier.com, http://www.elsevier.com/locate/shpsa/, Fax: 011 44 1865 843010) pp. 91-103 - issn: 0028-3908 - wos: WOS:000340853600011 (27) - scopus: 2-s2.0-84902152379 (27)

11573/1115578 - 2013 - [Genetics and epigenetics of schizophrenia]
Fabi, E; Fusco, A; Valiante, M; Celli, R - 01a Articolo in rivista
paper: LA CLINICA TERAPEUTICA (Roma : Società editrice Universo) pp. e319-24- - issn: 1972-6007 - wos: WOS:000325617700014 (7) - scopus: 2-s2.0-84885773009 (8)

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