Format

Send to

Choose Destination
Mol Neurobiol. 2017 Mar;54(2):1092-1100. doi: 10.1007/s12035-016-9728-2. Epub 2016 Jan 23.

Restrained Phosphatidylcholine Synthesis in a Cellular Model of Down's Syndrome is Associated with the Overexpression of Dyrk1A.

Author information

1
Departamento de Bioquímica y Biología Molecular, Instituto de Investigación Biomédica de Salamanca (IBSAL), Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Salamanca, Salamanca, Spain.
2
Departamento de Bioquímica y Biología Molecular, Instituto de Investigación Biomédica de Salamanca (IBSAL), Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Salamanca, Salamanca, Spain. anvecri@usal.es.

Abstract

Aberrant formation of the cerebral cortex could be attributed to the lack of suitable substrates that direct the migration of neurons. Previous work carried out at our laboratory has shown that oleic acid is a neurotrophic factor. In order to characterize the effect of oleic acid in a cellular model of Down's syndrome (DS), here, we used immortalized cell lines derived from the cortex of trisomy Ts16 and euploid mice. We report that in the plasma membrane of euploid cells, an increase in phosphatidylcholine concentrations occurs in the presence of oleic acid. However, in trisomic cells, oleic acid failed to increase phosphatidylcholine incorporation into the plasma membrane. Gene expression analysis of trisomic cells revealed that the phosphatidylcholine biosynthetic pathway was deregulated. Taken together, these results suggest that the overdose of specific genes in trisomic lines delays differentiation in the presence of oleic acid. The dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1A (DYRK1A) gene is located on human chromosome 21. DYRK1A contributes to intellectual disability and the early onset of Alzheimer's disease in DS patients. Here, we explored the potential role of Dyrk1A in the reduction of phosphatidylcholine concentrations in trisomic cells in the presence of oleic acid. The downregulation of Dyrk1A by small interfering RNA (siRNA) in trisomic cells returned phosphatidylcholine concentrations up to similar levels to those of euploid cells in the presence of oleic acid. Thus, our results highlight the role of Dyrk1A in brain development through the modulation of phosphatidylcholine location, levels and synthesis.

KEYWORDS:

Differentiation; Down’s syndrome; Dyrk1A; Oleic acid; Phosphatidylcholine

PMID:
26803494
DOI:
10.1007/s12035-016-9728-2
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center