Cargando…

Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates

Attention deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by alterations in the mesocorticolimbic and nigrostriatal dopaminergic pathways. Polymorphisms in the Synapsin III (Syn III) gene can associate with ADHD onset and even affect the therapeutic response...

Descripción completa

Detalles Bibliográficos
Autores principales: Faustini, Gaia, Longhena, Francesca, Muscò, Alessia, Bono, Federica, Parrella, Edoardo, La Via, Luca, Barbon, Alessandro, Pizzi, Marina, Onofri, Franco, Benfenati, Fabio, Missale, Cristina, Memo, Maurizio, Zizioli, Daniela, Bellucci, Arianna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739466/
https://www.ncbi.nlm.nih.gov/pubmed/36497160
http://dx.doi.org/10.3390/cells11233902
_version_ 1784847812966481920
author Faustini, Gaia
Longhena, Francesca
Muscò, Alessia
Bono, Federica
Parrella, Edoardo
La Via, Luca
Barbon, Alessandro
Pizzi, Marina
Onofri, Franco
Benfenati, Fabio
Missale, Cristina
Memo, Maurizio
Zizioli, Daniela
Bellucci, Arianna
author_facet Faustini, Gaia
Longhena, Francesca
Muscò, Alessia
Bono, Federica
Parrella, Edoardo
La Via, Luca
Barbon, Alessandro
Pizzi, Marina
Onofri, Franco
Benfenati, Fabio
Missale, Cristina
Memo, Maurizio
Zizioli, Daniela
Bellucci, Arianna
author_sort Faustini, Gaia
collection PubMed
description Attention deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by alterations in the mesocorticolimbic and nigrostriatal dopaminergic pathways. Polymorphisms in the Synapsin III (Syn III) gene can associate with ADHD onset and even affect the therapeutic response to the gold standard ADHD medication, methylphenidate (MPH), a monoamine transporter inhibitor whose efficacy appears related with the stimulation of brain-derived neurotrophic factor (BDNF). Interestingly, we previously showed that MPH can bind Syn III, which can regulate neuronal development. These observations suggest that Syn III polymorphism may impinge on ADHD onset and response to therapy by affecting BDNF-dependent dopaminergic neuron development. Here, by studying zebrafish embryos exposed to Syn III gene knock-down (KD), Syn III knock-out (ko) mice and human induced pluripotent stem cells (iPSCs)-derived neurons subjected to Syn III RNA interference, we found that Syn III governs the earliest stages of dopaminergic neurons development and that this function is conserved in vertebrates. We also observed that in mammals Syn III exerts this function acting upstream of brain-derived neurotrophic factor (BDNF)- and cAMP-dependent protein kinase 5 (Cdk5)-stimulated dendrite development. Collectively, these findings own significant implications for deciphering the biological basis of ADHD.
format Online
Article
Text
id pubmed-9739466
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97394662022-12-11 Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates Faustini, Gaia Longhena, Francesca Muscò, Alessia Bono, Federica Parrella, Edoardo La Via, Luca Barbon, Alessandro Pizzi, Marina Onofri, Franco Benfenati, Fabio Missale, Cristina Memo, Maurizio Zizioli, Daniela Bellucci, Arianna Cells Article Attention deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by alterations in the mesocorticolimbic and nigrostriatal dopaminergic pathways. Polymorphisms in the Synapsin III (Syn III) gene can associate with ADHD onset and even affect the therapeutic response to the gold standard ADHD medication, methylphenidate (MPH), a monoamine transporter inhibitor whose efficacy appears related with the stimulation of brain-derived neurotrophic factor (BDNF). Interestingly, we previously showed that MPH can bind Syn III, which can regulate neuronal development. These observations suggest that Syn III polymorphism may impinge on ADHD onset and response to therapy by affecting BDNF-dependent dopaminergic neuron development. Here, by studying zebrafish embryos exposed to Syn III gene knock-down (KD), Syn III knock-out (ko) mice and human induced pluripotent stem cells (iPSCs)-derived neurons subjected to Syn III RNA interference, we found that Syn III governs the earliest stages of dopaminergic neurons development and that this function is conserved in vertebrates. We also observed that in mammals Syn III exerts this function acting upstream of brain-derived neurotrophic factor (BDNF)- and cAMP-dependent protein kinase 5 (Cdk5)-stimulated dendrite development. Collectively, these findings own significant implications for deciphering the biological basis of ADHD. MDPI 2022-12-02 /pmc/articles/PMC9739466/ /pubmed/36497160 http://dx.doi.org/10.3390/cells11233902 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Faustini, Gaia
Longhena, Francesca
Muscò, Alessia
Bono, Federica
Parrella, Edoardo
La Via, Luca
Barbon, Alessandro
Pizzi, Marina
Onofri, Franco
Benfenati, Fabio
Missale, Cristina
Memo, Maurizio
Zizioli, Daniela
Bellucci, Arianna
Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates
title Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates
title_full Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates
title_fullStr Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates
title_full_unstemmed Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates
title_short Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates
title_sort synapsin iii regulates dopaminergic neuron development in vertebrates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739466/
https://www.ncbi.nlm.nih.gov/pubmed/36497160
http://dx.doi.org/10.3390/cells11233902
work_keys_str_mv AT faustinigaia synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT longhenafrancesca synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT muscoalessia synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT bonofederica synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT parrellaedoardo synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT lavialuca synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT barbonalessandro synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT pizzimarina synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT onofrifranco synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT benfenatifabio synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT missalecristina synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT memomaurizio synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT ziziolidaniela synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates
AT bellucciarianna synapsiniiiregulatesdopaminergicneurondevelopmentinvertebrates