Molecular Neurobiology

, Volume 46, Issue 2, pp 297–303

BDNF and DYRK1A Are Variable and Inversely Correlated in Lymphoblastoid Cell Lines from Down Syndrome Patients

  • Asma Tlili
  • Alexander Hoischen
  • Clémentine Ripoll
  • Eva Benabou
  • Anne Badel
  • Anne Ronan
  • Renaud Touraine
  • Yann Grattau
  • Samantha Stora
  • Bregje van Bon
  • Bert de Vries
  • Björn Menten
  • Nele Bockaert
  • Joseph Gecz
  • Stylianos E. Antonarakis
  • Dominique Campion
  • Marie-Claude Potier
  • Henri Bléhaut
  • Jean-Maurice Delabar
  • Nathalie Janel
Article

DOI: 10.1007/s12035-012-8284-7

Cite this article as:
Tlili, A., Hoischen, A., Ripoll, C. et al. Mol Neurobiol (2012) 46: 297. doi:10.1007/s12035-012-8284-7

Abstract

Down syndrome or trisomy 21 is the most common genetic disorder leading to mental retardation. One feature is impaired short- and long-term spatial memory, which has been linked to altered brain-derived neurotrophic factor (BDNF) levels. Mouse models of Down syndrome have been used to assess neurotrophin levels, and reduced BDNF has been demonstrated in brains of adult transgenic mice overexpressing Dyrk1a, a candidate gene for Down syndrome phenotypes. Given the link between DYRK1A overexpression and BDNF reduction in mice, we sought to assess a similar association in humans with Down syndrome. To determine the effect of DYRK1A overexpression on BDNF in the genomic context of both complete trisomy 21 and partial trisomy 21, we used lymphoblastoid cell lines from patients with complete aneuploidy of human chromosome 21 (three copies of DYRK1A) and from patients with partial aneuploidy having either two or three copies of DYRK1A. Decreased BDNF levels were found in lymphoblastoid cell lines from individuals with complete aneuploidy as well as those with partial aneuploidies conferring three DYRK1A alleles. In contrast, lymphoblastoid cell lines from individuals with partial trisomy 21 having only two DYRK1A copies displayed increased BDNF levels. A negative correlation was also detected between BDNF and DYRK1A levels in lymphoblastoid cell lines with complete aneuploidy of human chromosome 21. This finding indicates an upward regulatory role of DYRK1A expression on BDNF levels in lymphoblastoid cell lines and emphasizes the role of genetic variants associated with psychiatric disorders.

Keywords

Down syndromeDYRK1ABDNFLymphoblastoid cell linesmRNAProtein

Abbreviations

BDNF

Brain-derived neurotrophic factor

DS

Down syndrome

LCLs

Lymphoblastoid cell lines

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Asma Tlili
    • 1
  • Alexander Hoischen
    • 2
  • Clémentine Ripoll
    • 1
  • Eva Benabou
    • 1
  • Anne Badel
    • 3
  • Anne Ronan
    • 4
  • Renaud Touraine
    • 5
  • Yann Grattau
    • 6
  • Samantha Stora
    • 6
  • Bregje van Bon
    • 2
  • Bert de Vries
    • 2
  • Björn Menten
    • 7
  • Nele Bockaert
    • 8
  • Joseph Gecz
    • 9
  • Stylianos E. Antonarakis
    • 10
  • Dominique Campion
    • 11
  • Marie-Claude Potier
    • 12
  • Henri Bléhaut
    • 13
  • Jean-Maurice Delabar
    • 1
  • Nathalie Janel
    • 14
  1. 1.Unit of Functional and Adaptive Biology (BFA), Sorbonne Paris Cité, Univ. Paris DiderotEAC-CNRS 4413ParisFrance
  2. 2.Department of Human GeneticsRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.UMR-S 973, Molécule Thérapeutique in SilicoUniversity Paris DiderotParisFrance
  4. 4.Hunter Genetics UnitWaratahAustralia
  5. 5.Service de GénétiqueCHU-Hôpital NordSaint EtienneFrance
  6. 6.Institut Jérôme LejeuneParisFrance
  7. 7.Center for Medical GeneticsGhent University Hospital–UZ GentGhentBelgium
  8. 8.Department for Developmental DisordersGhent University Hospital–UZ GentGhentBelgium
  9. 9.Australia School of Paediatrics and Reproductive HealthUniversity of AdelaideAdelaideAustralia
  10. 10.Department of Genetic Medicine and DevelopmentUniversity of GenevaGenevaSwitzerland
  11. 11.Inserm U614, Faculty of MedicineInstitute for Biomedical ResearchRouenFrance
  12. 12.CRICM, CNRS UMR7225, UPMC, INSERM UMR975Hôpital de la Pitié-SalpêtrièreParisFrance
  13. 13.Fondation Jérome LejeuneParisFrance
  14. 14.Laboratoire BFAUniversité Paris DiderotParis cedex 13France