Penna, Eduardo (2021) Involvement of the serotonin receptor 7 in synaptic plasticity in the nervous system. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Involvement of the serotonin receptor 7 in synaptic plasticity in the nervous system |
| Autori: | Autore Email Penna, Eduardo edu.penna@virgilio.it |
| Data: | 5 Luglio 2021 |
| Numero di pagine: | 114 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Biologia |
| Dottorato: | Biologia |
| Ciclo di dottorato: | 33 |
| Coordinatore del Corso di dottorato: | nome email Cozzolino, Salvatore cozzolin@unina.it |
| Tutor: | nome email Crispino, Marianna [non definito] |
| Data: | 5 Luglio 2021 |
| Numero di pagine: | 114 |
| Parole chiave: | serotonin receptor 7; synaptic plasticity; Angelman Syndrome |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/09 - Fisiologia |
| Depositato il: | 23 Lug 2021 10:47 |
| Ultima modifica: | 07 Giu 2023 10:47 |
| URI: | http://www.fedoa.unina.it/id/eprint/13756 |
Abstract
The serotonin receptor 7 (5-HT7R) is a G protein-coupled receptor (GPCR) involved in many physiological events of the nervous system, such as learning and memory. It is also associated with several neurological and neurodevelopmental disorders, including Autism Spectrum Disorders (ASD). Among these pathologies, Angelman Syndrome (AS) is a rare neurodevelopmental disorder with a high comorbidity with ASD, especially with regards to developmental delay and language impairment. Interestingly, several pathways altered in this disease are positively regulated by 5-HT7R. Therefore, agonists of 5-HT7R could be considered as possible candidates for the development of innovative drugs to ameliorate AS symptoms. To this aim, we identified and characterized several 5-HT7R ligands and demonstrated that their residence time is structure-dependent and related to the polarity of the aryl moiety linked to their piperazine ring. In addition, our data on neurite outgrowth in neuronal primary cultures from different brain regions suggest that the residence time of these 5-HT7R ligands correlates with their kinetics of action. Using synaptosomes an in vitro model of presynaptic terminals, we observed that the stimulation of 5-HT7R finely regulates processes involved in synaptic plasticity, such as local synthesis and secretion of selected proteins. Finally, we demonstrated that stimulation of 5-HT7R was able to rescue LTP and behavioral impairments in a mouse model of AS. Altogether, our results underline the key role played by 5-HT7R in synaptic plasticity, indicating that this receptor represents a potential innovative target for pharmacological treatments of neurodevelopmental diseases characterized by altered connectivity/plasticity such as AS.
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