BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down syndrome patients.
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.
Unit of Functional and Adaptive Biology, Sorbonne Paris Cité, Univ. Paris Diderot, EAC-CNRS 4413, 75013 Paris, France.
Asma
A
Tlili
Alexander
A
Hoischen
Clémentine
C
Ripoll
Eva
E
Benabou
Anne
A
Badel
Anne
A
Ronan
Renaud
R
Touraine
Yann
Y
Grattau
Samantha
S
Stora
Bregje
B
van Bon
Bert
B
de Vries
Björn
B
Menten
Nele
N
Bockaert
Joseph
J
Gecz
Stylianos E
SE
Antonarakis
Dominique
D
Campion
Marie-Claude
MC
Potier
Henri
H
Bléhaut
Jean-Maurice
JM
Delabar
Nathalie
N
Janel
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000378:metabolism*; D002460:Cell Line; D002869:Chromosome Aberrations; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004314:Down Syndrome / Q000097:blood / Q000201:enzymology*; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology*; D051379:Mice; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000097603:Dyrk Kinases
D019208:Brain-Derived Neurotrophic Factor; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases