CHIARA URBINATI

Dottoressa di ricerca

ciclo: XXXVI


co-supervisore: Dott.ssa Bianca De Filippis

Titolo della tesi: Targeting brain mitochondrial bioenergetics as an attractive therapeutic avenue for Rett syndrome: evidence from female mouse models

Mitochondrial metabolism plays a crucial role in the regulation of brain function and behaviour. Many studies point towards a critical involvement of alterations in brain mitochondrial bioenergetics in the pathogenesis of a broad variety of conditions, including early-onset neurological diseases such as Rett syndrome (RTT), a rare genetic disorder. RTT patients are mainly females and manifest cognitive and motor impairments paired with physiological complications, since infancy. Defective brain mitochondrial energy metabolism, quality control and antioxidant defense have been identified in RTT patients and mouse models. The present thesis aimed to verify whether the rescue of brain mitochondrial bioenergetic alterations counteracts the neuropathological phenotype of RTT female mouse models. Three compounds, the anti-diabetic drug Metformin, the RhoGTPase activator CNF1 and the cannabinoid receptor 1 inhibitor Rimonabant, were selected for their recognized capability to modulate brain mitochondrial respiratory chain complex activity and their effects on the neuropathological phenotype of fully symptomatic RTT mice were addressed as an efficacy index. As expected, all the compounds restored mitochondrial dysfunctions in RTT mouse brain. In all three studies, such a restoration was accompanied by a selective improvement of cognitive abilities, while beneficial effects on RTT-related phenotypical alterations were not observed. Present findings corroborate an intimate connection between mitochondrial health and cognition in RTT context. The molecular investigation of mechanisms underlying the effects of the treatments suggests that restoration of the mitochondrial quality control may explain the beneficial outcomes of all the molecules tested on the defective brain mitochondria bioenergetics, highlighting a promising therapeutic target to treat RTT. Future studies will have to clarify whether targeting mitochondria during early life could provide better therapeutic efficacy for RTT. The generalization of our findings to other RTT-like diseases should be also addressed, in order to open up novel therapeutic opportunities for a wide range of conditions.

Produzione scientifica

11573/1696317 - 2023 - Precocious warning signs of Rett syndrome and Cdkl5 deficiency disorder: characterization of the early post-natal behavioural phenotype of mouse models.
Urbinati, C.; Cosentino, L.; De Matteis, A.; De Filippis, B. - 04d Abstract in atti di convegno
congresso: 56° Convegno annuale della International society for developmental psychobiology (ISDP) (Utrecht (NL))
libro: Precocious warning signs of Rett syndrome and Cdkl5 deficiency disorder: characterization of the early post-natal behavioural phenotype of mouse models. - ()

11573/1669730 - 2023 - Chronic treatment with the anti-diabetic drug metformin rescues impaired brain mitochondrial activity and selectively ameliorates defective cognitive flexibility in a female mouse model of Rett syndrome
Urbinati, Chiara; Lanzillotta, Chiara; Cosentino, Livia; Valenti, Daniela; Quattrini, Maria Cristina; Di Crescenzo, Livia; Prestia, Francesca; Pietraforte, Donatella; Perluigi, Marzia; Di Domenico, Fabio; Vacca, Rosa Anna; De Filippis, Bianca - 01a Articolo in rivista
rivista: NEUROPHARMACOLOGY ([Oxford] : Elsevier Ltd.) pp. 109350- - issn: 1873-7064 - wos: WOS:000895904100001 (2) - scopus: 2-s2.0-85143870753 (1)

11573/1657453 - 2022 - Serotonin receptor 7 stimulation rescues fear generalization in a male mouse model of post-traumatic stress disorder
Di Crescenzo, L.; Cosentino, L.; Urbinati, C.; Lacivita, E.; Leopoldo, M.; De Filippis, B. - 04c Atto di convegno in rivista
rivista: NEUROSCIENCE APPLIED (Amsterdam: Elsevier B.V) pp. 100043- - issn: 2772-4085 - wos: (0) - scopus: (0)
congresso: Workshop for Early Career Scientists in Europe organized by European College of Neuropsychopharmacology (ECNP), (Nice (FR))

11573/1672906 - 2022 - Pharmacological stimulation of the serotonin receptor 7 rescues fear generalization in a PTSD mouse model carrying a truncated form of MeCP2.
Di Crescenzo, L.; Cosentino, L.; Urbinati, C.; Lacivita, E.; Leopoldo, M.; De Filippis, B. - 04d Abstract in atti di convegno
congresso: Federation of European Neuroscience Societies (FENS) 2022 (Paris (FR))
libro: Abstractbook - ()

11573/1657450 - 2022 - Treatment with FRAX486 rescues neurobehavioral and metabolic alterations in a female mouse model of CDKL5 deficiency disorder
Fuchs, Claudia; Cosentino, Livia; Urbinati, Chiara; Talamo, Maria Cristina; Medici, Giorgio; Quattrini, Maria Cristina; Mottolese, Nicola; Pietraforte, Donatella; Fuso, Andrea; Ciani, Elisabetta; De Filippis, Bianca - 01a Articolo in rivista
rivista: CNS NEUROSCIENCE & THERAPEUTICS (Oxford : Blackwell, 2008-) pp. 1718-1732 - issn: 1755-5930 - wos: WOS:000836897900001 (2) - scopus: 2-s2.0-85135447896 (2)

11573/1672908 - 2022 - Treatment with the CB1R antagonist rimonabant rescues brain mitochondrial dysfunction via inhibition of intra-mitochondrial protein kinase A signalling in a mouse model of Rett syndrome
Urbinati, C.; Cosentino, L.; Valenti, D.; De Rasmo, D.; Signorile, A.; Pellas, M.; Vacca, R. A.; De Filippis, B. - 04d Abstract in atti di convegno
congresso: Federation of European Neuroscience Societies (FENS) 2022 (Paris (FR))
libro: Abstractbook - ()

11573/1672899 - 2022 - A systemic treatment with a cannabinoid receptor type 1 (CB1) antagonist rescues brain mitochondrial activity dysfunction in a symptomatic mouse model of Rett syndrome.
Urbinati, Chiara; Cosentino, Livia; Valenti, Daniela; De Rasmo, Domenico; Signorile, Anna; Pellas, Mattia; Anna Vacca, Rosa; De Filippis, Bianca - 04d Abstract in atti di convegno
congresso: Jacques Monod Conference (Roscoff (FR))
libro: Abstractbook - ()

11573/1657452 - 2021 - Pharmacological stimulation of the serotonin receptor 7 rescues PTSD-like behavioural alterations in male mice carrying a truncated form of mecp2.
Di Crescenzo, Livia; Cosentino, Livia; Urbinati, Chiara; Lacivita, Enza; Leopoldo, Marco; De Filippis, Bianca - 04d Abstract in atti di convegno
congresso: 49th Meeting of European Brain and Behaviour Society (EBBS) (Lausanne (CH))
libro: EBBS Abstractbook - ()

11573/1519774 - 2021 - P.219 The antidiabetic drug metformin improves cognitive flexibility deficits in a female mouse model of Rett syndrome
Urbinati, C.; Cosentino, L.; Evoli, M.; De Filippis, B. - 01h Abstract in rivista
rivista: EUROPEAN NEUROPSYCHOPHARMACOLOGY (Elsevier BV:PO Box 211, 1000 AE Amsterdam Netherlands:011 31 20 4853757, 011 31 20 4853642, 011 31 20 4853641, EMAIL: nlinfo-f@elsevier.nl, INTERNET: http://www.elsevier.nl, Fax: 011 31 20 4853598) pp. S28-S29 - issn: 0924-977X - wos: WOS:000624608100039 (0) - scopus: (0)

11573/1605799 - 2021 - Treatment with the bacterial toxin CNF1 selectively rescues cognitive and brain mitochondrial deficits in a female mouse model of Rett syndrome carrying a MeCP2-null mutation
Urbinati, C.; Cosentino, L.; Germinario, E. A. P.; Valenti, D.; Vigli, D.; Ricceri, L.; Laviola, G.; Fiorentini, C.; Vacca, R. A.; Fabbri, A.; De Filippis, B. - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. - - issn: 1661-6596 - wos: WOS:000671220100001 (5) - scopus: 2-s2.0-85108295315 (5)

11573/1605804 - 2021 - Cognitive flexibility defects displayed by a female mouse model of Rett syndrome.
Urbinati, Chiara - 04d Abstract in atti di convegno
congresso: European Neuroscience Conference by Doctoral Students (ENCODS) 2021 (Virtual)
libro: Abstractbook - ()

11573/1605803 - 2021 - Long-term treatment with the antidiabetic drug metformin ameliorates cognitive flexibility deficits in a female mouse model of Rett syndrome.
Urbinati, Chiara; Cosentino, Livia; De Filippis, Bianca - 04d Abstract in atti di convegno
congresso: 49th Meeting of European Brain and Behaviour Society (EBBS) (Lausanne, Switzerland)
libro: Abstractbook - ()

11573/1605805 - 2021 - The first-line antidiabetic drug Metformin improves the impaired cognitive flexibility in a female mouse model of Rett syndrome.
Urbinati, Chiara; Cosentino, Livia; De Filippis, Bianca - 04d Abstract in atti di convegno
congresso: 19th SINS National Congress (Virtual)
libro: Abstractbook - ()

11573/1487099 - 2020 - MECP2: a sex dependent actor in stress regulation of memory
Cosentino, Livia; Bellia, Fabio; Pavoncello, Nicole; Urbinati, Chiara; D'addario, Claudio; De Filippis, Bianca - 04d Abstract in atti di convegno
congresso: Neuroscience PhD Meeting 2020, SINS (Naples, Italy)
libro: PhD national meeting, SINS - ()

11573/1406171 - 2020 - Potential therapeutic value of the anti-diabetic drug metformin in a mouse model of Rett syndrome: a preclinical study
Urbinati, Chiara; Zuliani, Ilaria; Valenti, Daniela; Cristina Quattrini, Maria; Cosentino, Livia; Medici, Vanessa; Pietraforte, Donatella; Di Domenico, Fabio; Perluigi, Marzia; Anna Vacca, Rosa; De Filippis, Bianca - 04d Abstract in atti di convegno
congresso: FENS 2020 virtual forum (virtual)
libro: FENS 2020 virtual forum - ()

11573/1406139 - 2020 - The anti-diabetic drug metformin rescues aberrant mitochondrial activity and restrains oxidative stress in a female mouse model of rett syndrome
Zuliani, Ilaria; Urbinati, Chiara; Valenti, Daniela; Cristina Quattrini, Maria; Medici, Vanessa; Cosentino, Livia; Pietraforte, Donatella; Di Domenico, Fabio; Perluigi, Marzia; Anna Vacca, Rosa; De Filippis, Bianca - 01a Articolo in rivista
rivista: JOURNAL OF CLINICAL MEDICINE (MDPI Publishing, Basel, Switzerland) pp. - - issn: 2077-0383 - wos: WOS:000549226700001 (14) - scopus: 2-s2.0-85102223213 (14)

11573/1348645 - 2019 - Pharmacological inhibition of p21-Activated Kinase rescues the behavioral phenotype in a female mouse model of CDKL5 Deficiency Disorder
Cristina Talamo, Maria; Pellas, Mattia; Urbinati, Chiara; Cosentino, Livia; De Filippis, Bianca - 04d Abstract in atti di convegno
congresso: 6th European Conference on Behaviour and Cognition, (Padova)
libro: 6th European Conference on Behaviour and Cognition - ()

11573/1286405 - 2019 - Pharmacological inhibition of p21-Activated Kinase rescues the behavioural phenotype in a female mouse model of CDKL5 Deficiency Disorder
Talamo, M. C.; Pellas, M.; Urbinati, C.; Cosentino, L.; De Filippis, B - 04d Abstract in atti di convegno
congresso: 48th Meeting of the European Brain and Behaviour Society (Prague, Czech Republic)
libro: 48th Meeting of the European Brain and Behaviour Society - ()

11573/1348640 - 2019 - Metformin treatment rescues aberrant mitochondrial activity and oxidative stress status in the brain of female mouse model of Rett syndrome
Urbinati, Chiara; Zuliani, Ilaria; Valenti, Daniela; Medici, Vanessa; Cosentino, Livia; Vigli, Daniele; Di Domenico, Fabio; Perluigi, Marzia; Anna Vacca, Rosa; De Filippis, Bianca - 04d Abstract in atti di convegno
congresso: 6th European Conference on Behaviour and Cognition, (Padova)
libro: 6th European Conference on Behaviour and Cognition - ()

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