BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down syndrome patients

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

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Title		BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down syndrome patients
Authors		Tlili, Asma Hoischen, Alexander Ripoll, Clémentine Benabou, Eva Badel, Anne Ronan, Anne Touraine, Renaud Grattau, Yann Stora, Samantha van Bon, Bregje de Vries, Bert Menten, Björn Bockaert, Nele Gecz, Joseph Antonarakis, Stylianos Campion, Dominique Potier, Marie-Claude Bléhaut, Henri Delabar, Jean-Maurice Janel, Nathalie show all authors [1 - 20]
Published in		Molecular Neurobiology. 2012, vol. 46, no. 2, p. 297-303
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		Animals — Brain-Derived Neurotrophic Factor/blood/metabolism — Cell Line — Chromosome Aberrations — Chromosomes, Human, Pair 21/genetics — Down Syndrome/blood/enzymology — Humans — Lymphocytes/enzymology — Mice — Middle Aged — Protein-Serine-Threonine Kinases/metabolism — Protein-Tyrosine Kinases/metabolism
Identifiers		DOI: 10.1007/s12035-012-8284-7 PMID: 22669612
Full text		Article (Published version) (167 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
Research group		Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
Citation (ISO format)		TLILI, Asma et al. BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down syndrome patients. In: Molecular Neurobiology, 2012, vol. 46, n° 2, p. 297-303. https://archive-ouverte.unige.ch/unige:34644