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. © 2022 by the authors.
Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates
Parrella, Edoardo;
2022-01-01
Abstract
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. © 2022 by the authors.File | Dimensione | Formato | |
---|---|---|---|
Faustini et al. Cells 2022.pdf
non disponibili
Licenza:
Dominio pubblico
Dimensione
3.54 MB
Formato
Adobe PDF
|
3.54 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.