Penna, Eduardo (2021) Involvement of the serotonin receptor 7 in synaptic plasticity in the nervous system. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Resource language: English
Title: Involvement of the serotonin receptor 7 in synaptic plasticity in the nervous system
Creators:
CreatorsEmail
Penna, Eduardoedu.penna@virgilio.it
Date: 5 July 2021
Number of Pages: 114
Institution: Università degli Studi di Napoli Federico II
Department: Biologia
Dottorato: Biologia
Ciclo di dottorato: 33
Coordinatore del Corso di dottorato:
nomeemail
Cozzolino, Salvatorecozzolin@unina.it
Tutor:
nomeemail
Crispino, MariannaUNSPECIFIED
Date: 5 July 2021
Number of Pages: 114
Keywords: serotonin receptor 7; synaptic plasticity; Angelman Syndrome
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/09 - Fisiologia
Date Deposited: 23 Jul 2021 10:47
Last Modified: 07 Jun 2023 10:47
URI: http://www.fedoa.unina.it/id/eprint/13756

Collection description

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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