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...
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MDPI AG
2022-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3902 |
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| author | Gaia Faustini Francesca Longhena Alessia Muscò Federica Bono Edoardo Parrella Luca La Via Alessandro Barbon Marina Pizzi Franco Onofri Fabio Benfenati Cristina Missale Maurizio Memo Daniela Zizioli Arianna Bellucci |
| author_facet | Gaia Faustini Francesca Longhena Alessia Muscò Federica Bono Edoardo Parrella Luca La Via Alessandro Barbon Marina Pizzi Franco Onofri Fabio Benfenati Cristina Missale Maurizio Memo Daniela Zizioli Arianna Bellucci |
| author_sort | Gaia Faustini |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T17:50:02Z |
| format | Article |
| id | doaj.art-10960a49c8414beb9bede2aa594d5154 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:50:02Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-10960a49c8414beb9bede2aa594d51542023-11-24T10:45:43ZengMDPI AGCells2073-44092022-12-011123390210.3390/cells11233902Synapsin III Regulates Dopaminergic Neuron Development in VertebratesGaia Faustini0Francesca Longhena1Alessia Muscò2Federica Bono3Edoardo Parrella4Luca La Via5Alessandro Barbon6Marina Pizzi7Franco Onofri8Fabio Benfenati9Cristina Missale10Maurizio Memo11Daniela Zizioli12Arianna Bellucci13Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Experimental Medicine, University of Genova, Via Leon Battista Alberti 2, 16132 Genova, ItalyIRCSS Policlinico San Martino Hospital, Largo Rosanna Benzi 10, 16132 Genova, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyAttention 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.https://www.mdpi.com/2073-4409/11/23/3902synapsin IIIdopaminergic neuronsattention deficit and hyperactivity disorderneurodevelopment |
| spellingShingle | Gaia Faustini Francesca Longhena Alessia Muscò Federica Bono Edoardo Parrella Luca La Via Alessandro Barbon Marina Pizzi Franco Onofri Fabio Benfenati Cristina Missale Maurizio Memo Daniela Zizioli Arianna Bellucci Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates Cells synapsin III dopaminergic neurons attention deficit and hyperactivity disorder neurodevelopment |
| 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 | synapsin III dopaminergic neurons attention deficit and hyperactivity disorder neurodevelopment |
| url | https://www.mdpi.com/2073-4409/11/23/3902 |
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