Prenatal treatment with EGCG enriched green tea extract rescues GAD67 related developmental and cognitive defects in Down syndrome mouse models

Scientific Reports
Benoit SouchetJean Maurice Delabar

Abstract

Down syndrome is a common genetic disorder caused by trisomy of chromosome 21. Brain development in affected foetuses might be improved through prenatal treatment. One potential target is DYRK1A, a multifunctional kinase encoded by chromosome 21 that, when overexpressed, alters neuronal excitation-inhibition balance and increases GAD67 interneuron density. We used a green tea extract enriched in EGCG to inhibit DYRK1A function only during gestation of transgenic mice overexpressing Dyrk1a (mBACtgDyrk1a). Adult mice treated prenatally displayed reduced levels of inhibitory markers, restored VGAT1/VGLUT1 balance, and rescued density of GAD67 interneurons. Similar results for gabaergic and glutamatergic markers and interneuron density were obtained in Dp(16)1Yey mice, trisomic for 140 chromosome 21 orthologs; thus, prenatal EGCG exhibits efficacy in a more complex DS model. Finally, cognitive and behaviour testing showed that adult Dp(16)1Yey mice treated prenatally had improved novel object recognition memory but do not show improvement with Y maze paradigm. These findings provide empirical support for a prenatal intervention that targets specific neural circuitries.

References

May 18, 1990·Neuroscience Letters·K KobayashiD M Mann
Jul 1, 1984·Neurology·M H RossT L Kemper
Jan 22, 2003·The Biochemical Journal·Jenny BainPhilip Cohen
Jun 9, 2004·Neurobiology of Learning and Memory·Rebecca S HammondRobert W Stackman
Sep 17, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alexander M KleschevnikovWilliam C Mobley
Jun 1, 2005·Neuroscience Letters·Alberto C S Costa, Michael J Grybko
Jun 2, 2005·Trends in Neurosciences·Alfonso Represa, Yehezkel Ben-Ari
Jan 30, 2007·Journal of Agricultural and Food Chemistry·Lei-Chwen LinTung-Hu Tsai
Feb 27, 2007·Nature Neuroscience·Fabian FernandezC C Garner
Apr 4, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David M BannermanJohn N P Rawlins
Feb 27, 2009·PloS One·Faycal GuedjJean Maurice Delabar
Sep 10, 2009·Developmental Psychobiology·Maxine L RegerChristopher C Giza
Feb 17, 2010·Journal of Neural Transmission·D Pérez-CremadesEmilio Varea
Jul 20, 2010·Nature Neuroscience·Lina ChakrabartiTarik F Haydar
Dec 20, 2011·Experimental Neurology·Tyler K BestZygmunt Galdzicki
Jan 19, 2012·Journal of Neuroscience Research·Bozena Mazur-KoleckaJanusz Frackowiak
Feb 2, 2012·Neurobiology of Disease·Faycal GuedjJean Maurice Delabar
Apr 12, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Setsuko SaharaCharles F Stevens
Jul 6, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alexander M KleschevnikovWilliam C Mobley
Oct 27, 2012·Journal of Medical Genetics·Jean-Benoît CourcetChristel Thauvin-Robinet
Mar 1, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Carmen Martínez-CuéMaria-Clemencia Hernández
Sep 17, 2013·Molecular Nutrition & Food Research·Rafael de la TorreMara Dierssen
Jan 24, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Aurore ThomazeauOlivier J Manzoni
Feb 28, 2014·Current Opinion in Obstetrics & Gynecology·Faycal GuedjJean-Maurice Delabar
May 8, 2014·Neurobiology of Disease·Benoit SouchetJean Maurice Delabar
Nov 17, 2014·Neurochemical Research·Samuel Hernández-GonzálezEmilio Varea
Apr 1, 2015·Trends in Molecular Medicine·Jaewon KoJi Won Um
Sep 17, 2015·Human Molecular Genetics·Xiaoling JiangY Eugene Yu
Nov 6, 2015·Frontiers in Behavioral Neuroscience·Benoit SouchetJean Maurice Delabar
Mar 11, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joseph W GoodliffeTarik F Haydar
Jun 26, 2017·Neurobiology of Disease·Susana García-CerroCarmen Martínez-Cué
Sep 7, 2017·Proceedings of the National Academy of Sciences of the United States of America·Akiko Nakano-KobayashiMasatoshi Hagiwara
Oct 11, 2017·Free Radical Biology & Medicine·Javier Zorrilla de San MartinMarie-Claude Potier
Nov 25, 2017·Progress in Neuro-psychopharmacology & Biological Psychiatry·Austin A Coley, Wen-Jun Gao
Mar 7, 2018·Brain Pathology·Sandra GuidiRenata Bartesaghi
Mar 20, 2018·Neurobiology of Disease·Larisa V LysenkoAlexander M Kleschevnikov

Citations

Sep 2, 2020·Cellular and Molecular Life Sciences : CMLS·Amina Jamal LahamRaafat El-Awady
Feb 26, 2020·International Journal of Molecular Sciences·Yuchen GuNathalie Janel
Aug 8, 2020·Frontiers in Pediatrics·Laura AlmeidaMaría Dolores Gómez-Roig
Jan 24, 2021·Journal of Ethnopharmacology·Maciel da Costa AlvesJuliana Késsia Barbosa Soares
Feb 5, 2021·Redox Biology·M Pilar Bayona-BafaluyEduardo Ruiz-Pesini
Mar 7, 2021·Biomolecules·Chiara Lanzillotta, Fabio Di Domenico
Feb 27, 2021·Scientific Reports·John M StarbuckNeus Martínez-Abadías

Methods Mentioned

BETA
transgenic
dissector

Related Concepts

Biological Markers
Brain
Chromosomes
Cognition
Down Syndrome
Equilibrium
Hereditary Diseases
Interneurons
Laboratory mice
Mice, Transgenic

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