Effect of DYRK1A activity inhibition on development of neuronal progenitors isolated from Ts65Dn mice - PubMed (original) (raw)
. 2012 May;90(5):999-1010.
doi: 10.1002/jnr.23007. Epub 2012 Jan 18.
Affiliations
- PMID: 22252917
- DOI: 10.1002/jnr.23007
Effect of DYRK1A activity inhibition on development of neuronal progenitors isolated from Ts65Dn mice
Bozena Mazur-Kolecka et al. J Neurosci Res. 2012 May.
Abstract
Overexpression of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (DYRK1A), encoded by a gene located in the Down syndrome (DS) critical region, is considered a major contributor to developmental abnormalities in DS. DYRK1A regulates numerous genes involved in neuronal commitment, differentiation, maturation, and apoptosis. Because alterations of neurogenesis could lead to impaired brain development and mental retardation in individuals with DS, pharmacological normalization of DYRK1A activity has been postulated as DS therapy. We tested the effect of harmine, a specific DYRK1A inhibitor, on the development of neuronal progenitor cells (NPCs) isolated from the periventricular zone of newborn mice with segmental trisomy 16 (Ts65Dn mice), a mouse model for DS that overexpresses Dyrk1A by 1.5-fold. Trisomy did not affect the ability of NPCs to expand in culture. Twenty-four hours after stimulation of migration and neuronal differentiation, NPCs showed increased expression of Dyrk1A, particularly in the trisomic cultures. After 7 days, NPCs developed into a heterogeneous population of differentiating neurons and astrocytes that expressed Dyrk1A in the nuclei. In comparison with disomic cells, NPCs with trisomy showed premature neuronal differentiation and enhanced γ-aminobutyric acid (GABA)-ergic differentiation, but astrocyte development was unchanged. Harmine prevented premature neuronal maturation of trisomic NPCs but not acceleration of GABA-ergic development. In control NPCs, harmine treatment caused altered neuronal development of NPCs, similar to that in trisomic NPCs with Dyrk1A overexpression. This study suggests that pharmacological normalization of DYRK1A activity may have a potential role in DS therapy.
Copyright © 2012 Wiley Periodicals, Inc.
Similar articles
- Form of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A nonphosphorylated at tyrosine 145 and 147 is enriched in the nuclei of astroglial cells, adult hippocampal progenitors, and some cholinergic axon terminals.
Kida E, Walus M, Jarząbek K, Palminiello S, Albertini G, Rabe A, Hwang YW, Golabek AA. Kida E, et al. Neuroscience. 2011 Nov 10;195:112-27. doi: 10.1016/j.neuroscience.2011.08.028. Epub 2011 Aug 19. Neuroscience. 2011. PMID: 21878370 - Overexpression of DYRK1A inhibits choline acetyltransferase induction by oleic acid in cellular models of Down syndrome.
Hijazi M, Fillat C, Medina JM, Velasco A. Hijazi M, et al. Exp Neurol. 2013 Jan;239:229-34. doi: 10.1016/j.expneurol.2012.10.016. Epub 2012 Nov 1. Exp Neurol. 2013. PMID: 23124096 - Normalization of Dyrk1A expression by AAV2/1-shDyrk1A attenuates hippocampal-dependent defects in the Ts65Dn mouse model of Down syndrome.
Altafaj X, Martín ED, Ortiz-Abalia J, Valderrama A, Lao-Peregrín C, Dierssen M, Fillat C. Altafaj X, et al. Neurobiol Dis. 2013 Apr;52:117-27. doi: 10.1016/j.nbd.2012.11.017. Epub 2012 Dec 5. Neurobiol Dis. 2013. PMID: 23220201 - [Molecular Mechanism Underlying Abnormal Differentiation of Neural Progenitor Cells in the Developing Down Syndrome Brain].
Kurabayashi N, Sanada K. Kurabayashi N, et al. Yakugaku Zasshi. 2017;137(7):795-800. doi: 10.1248/yakushi.16-00236-1. Yakugaku Zasshi. 2017. PMID: 28674289 Review. Japanese. - Mental retardation and associated neurological dysfunctions in Down syndrome: a consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways.
Rachidi M, Lopes C. Rachidi M, et al. Eur J Paediatr Neurol. 2008 May;12(3):168-82. doi: 10.1016/j.ejpn.2007.08.010. Epub 2007 Oct 22. Eur J Paediatr Neurol. 2008. PMID: 17933568 Review.
Cited by
- Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.
Hogg EKJ, Findlay GM. Hogg EKJ, et al. FEBS Lett. 2023 Oct;597(19):2375-2415. doi: 10.1002/1873-3468.14723. Epub 2023 Sep 4. FEBS Lett. 2023. PMID: 37607329 Free PMC article. Review. - Serum microRNAs associated with concussion in football players.
Wyczechowska D, Harch PG, Mullenix S, Fannin ES, Chiappinelli BB, Jeansonne D, Lassak A, Bazan NG, Peruzzi F. Wyczechowska D, et al. Front Neurol. 2023 Apr 18;14:1155479. doi: 10.3389/fneur.2023.1155479. eCollection 2023. Front Neurol. 2023. PMID: 37144000 Free PMC article. - Regeneration of Pancreatic β-Cells for Diabetes Therapeutics by Natural DYRK1A Inhibitors.
Guo Y, Li L, Yao Y, Li H. Guo Y, et al. Metabolites. 2022 Dec 29;13(1):51. doi: 10.3390/metabo13010051. Metabolites. 2022. PMID: 36676976 Free PMC article. Review. - The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives.
Stagni F, Bartesaghi R. Stagni F, et al. Front Cell Neurosci. 2022 May 11;16:903729. doi: 10.3389/fncel.2022.903729. eCollection 2022. Front Cell Neurosci. 2022. PMID: 35634470 Free PMC article. Review. - Dyrk1a from Gene Function in Development and Physiology to Dosage Correction across Life Span in Down Syndrome.
Atas-Ozcan H, Brault V, Duchon A, Herault Y. Atas-Ozcan H, et al. Genes (Basel). 2021 Nov 20;12(11):1833. doi: 10.3390/genes12111833. Genes (Basel). 2021. PMID: 34828439 Free PMC article. Review.
Publication types
MeSH terms
Substances
Supplementary concepts
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical