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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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 |
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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 |
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