PMID- 36497160
OWN - NLM
STAT- MEDLINE
DCOM- 20221229
LR  - 20221229
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 23
DP  - 2022 Dec 2
TI  - Synapsin III Regulates Dopaminergic Neuron Development in Vertebrates.
LID - 10.3390/cells11233902 [doi]
LID - 3902
AB  - 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.
FAU - Faustini, Gaia
AU  - Faustini G
AUID- ORCID: 0000-0002-0751-3082
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Longhena, Francesca
AU  - Longhena F
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Musco, Alessia
AU  - Musco A
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Bono, Federica
AU  - Bono F
AUID- ORCID: 0000-0001-9716-5327
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Parrella, Edoardo
AU  - Parrella E
AUID- ORCID: 0000-0003-0365-5144
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - La Via, Luca
AU  - La Via L
AUID- ORCID: 0000-0002-8475-1551
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Barbon, Alessandro
AU  - Barbon A
AUID- ORCID: 0000-0002-1127-7764
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Pizzi, Marina
AU  - Pizzi M
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Onofri, Franco
AU  - Onofri F
AD  - Department of Experimental Medicine, University of Genova, Via Leon Battista 
      Alberti 2, 16132 Genova, Italy.
FAU - Benfenati, Fabio
AU  - Benfenati F
AUID- ORCID: 0000-0002-0653-8368
AD  - IRCSS Policlinico San Martino Hospital, Largo Rosanna Benzi 10, 16132 Genova, 
      Italy.
AD  - Italian Institute of Technology, Via Morego 30, 16163 Genova, Italy.
FAU - Missale, Cristina
AU  - Missale C
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Memo, Maurizio
AU  - Memo M
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Zizioli, Daniela
AU  - Zizioli D
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
FAU - Bellucci, Arianna
AU  - Bellucci A
AUID- ORCID: 0000-0002-9581-1919
AD  - Department of Molecular and Translational Medicine, University of Brescia, Viale 
      Europa 11, 25123 Brescia, Italy.
AD  - Laboratory for Preventive and Personalized Medicine, Department of Molecular and 
      Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, 
      Italy.
LA  - eng
GR  - 2017-1065/Ministry of Education, Universities and Research/
GR  - Ex 60% 2017-2020/University of Brescia/
GR  - PNR 2015-2020 PerMedNet/Ministry of Education, Universities and Research/
GR  - #10742.01/Michael J. Fox Foundation/
PT  - Journal Article
DEP - 20221202
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - VTD58H1Z2X (Dopamine)
RN  - 207ZZ9QZ49 (Methylphenidate)
RN  - 0 (Synapsins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Dopamine
MH  - *Dopaminergic Neurons/metabolism
MH  - Induced Pluripotent Stem Cells/metabolism
MH  - Methylphenidate/therapeutic use
MH  - Mice, Knockout
MH  - *Synapsins/genetics/metabolism
MH  - Zebrafish/metabolism
PMC - PMC9739466
OTO - NOTNLM
OT  - attention deficit and hyperactivity disorder
OT  - dopaminergic neurons
OT  - neurodevelopment
OT  - synapsin III
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/12 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/12/02
CRDT- 2022/12/11 01:03
PHST- 2022/10/26 00:00 [received]
PHST- 2022/11/17 00:00 [revised]
PHST- 2022/11/29 00:00 [accepted]
PHST- 2022/12/11 01:03 [entrez]
PHST- 2022/12/12 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/12/02 00:00 [pmc-release]
AID - cells11233902 [pii]
AID - cells-11-03902 [pii]
AID - 10.3390/cells11233902 [doi]
PST - epublish
SO  - Cells. 2022 Dec 2;11(23):3902. doi: 10.3390/cells11233902.