Methylphenidate effects on mice odontogenesis and connections with human odontogenesis
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ORIGINAL ARTICLE
Methylphenidate effects on mice odontogenesis and connections with human odontogenesis Karol Sartori Lima1 · Antônio Eduardo Sparça Salles1 · Gabriel de Araújo Costa1 · Márjori Frítola Yokoyama1 · Solange de Paula Ramos2 · Vanessa Rodrigues Paixão‑Côrtes3 · Renata Lúcia Leite Ferreira de Lima3 · Maria José Sparça Salles1 Received: 22 April 2020 / Accepted: 17 August 2020 © The Society of The Nippon Dental University 2020
Abstract The purpose of this study is to evaluate the effects of Methylphenidate exposure on mice odontogenesis and connect them by bioinformatics with human odontogenesis. Thirty-two pregnant Swiss mice were divided into treated group and control group, which received, respectively, 5 mg/kg of Methylphenidate and saline solution from the 5th to the 17th day of pregnancy. The mouse embryos tooth germs were analyzed through optical microscopy, and the data collected were analyzed statistically by Fisher’s exact test. The presence and similarity of Methylphenidate-associated genes (Pharmgkb database) in both organisms and their interaction with dental development genes (AmiGO2 database) were verified on STRING database. Rates of tooth germ malformations were higher in treated than in control group (Control: 18; Treated: 27; p = 0.035). Mouse embryo malformations were connected with 238 interactions between 69 dental development genes with 35 Methylphenidate genes. Fourteen interactions for four Methylphenidate genes with four dental development genes, with human experimental data, were connected with mouse phenotype data. By homology, the interactions and conservation of proteins/genes may indicate similar outcomes for both organisms. The exposure to Methylphenidate during pregnancy affected odontogenesis in mouse embryos and may affect human odontogenesis. The study of malformations in mice, with a bioinformatics approach, could contribute to understanding of the Methylphenidate effect on embryo development. These results may provide novel hypotheses for further testing and reinforce the FDA protocol: as Methylphenidate is included in category C, its use during pregnancy should be considered if the benefits outweigh the risks. Keywords Methylphenidate · Mice · Morphogenesis · Odontogenesis · Tooth germ
* Márjori Frítola Yokoyama [email protected]
Maria José Sparça Salles [email protected]
Karol Sartori Lima [email protected]
1
Department of General Biology, State University of Londrina (UEL), Km 380, Celso Garcia Cid Road, Londrina 86057‑970, Brazil
2
Department of Histology, State University of Londrina (UEL), Km 380, Celso Garcia Cid Road, Londrina 86057‑970, Brazil
3
PPGBioEvo, Institute of Biology, Federal University of Bahia (UFBA), 668, Barão de Jeremoabo Street, Salvador 40170‑115, Brazil
Antônio Eduardo Sparça Salles [email protected] Gabriel de Araújo Costa [email protected] Solange de Paula Ramos [email protected] Vanessa Rodrigues Paixão‑Côrtes [email protected] Renata Lúcia Leite Ferreira de Lima [email protected]
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