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Overexpression of the DYRK1A Gene (Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A) Induces Alterations of the Serotoninergic and Dopaminergic Processing in Murine Brain Tissues

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Abstract

Trisomy 21 (T21) or Down syndrome (DS) is the most common genetic disorder associated with intellectual disability and affects around 5 million persons worldwide. Neuroanatomical phenotypes associated with T21 include slight reduction of brain size and weight, abnormalities in several brain areas including spines dysgenesis, dendritic morphogenesis, and early neuroanatomical characteristics of Alzheimer’s disease. Monoamine neurotransmitters are involved in dendrites development, functioning of synapses, memory consolidation, and their levels measured in the cerebrospinal fluid, blood, or brain areas that are modified in individuals with T21. DYRK1A is one of the recognized key genes that could explain some of the deficits present in individuals with T21. We investigated by high-performance liquid chromatography with electrochemical detection the contents and processing of monoamines neurotransmitters in four brain areas of female and male transgenic mice for the Dyrk1a gene (mBactgDyrk1a). DYRK1A overexpression induced dramatic deficits in the serotonin contents of the four brain areas tested and major deficits in dopamine and adrenaline contents especially in the hypothalamus. These results suggest that DYRK1A overexpression might be associated with the modification of monoamines content found in individuals with T21 and reinforce the interest to target the level of DYRK1A expression as a therapeutic approach for persons with T21.

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Acknowledgements

We thank the personnel of Institut Jacques Monod animal facility for taking care of the animals for health and control. We thank for funding CNRS, the European Commission (AnEUploidy project LSHG-CT-2006-037627 and the AFRT (Association Française pour la Recherche sur la Trisomie 21) for grants (2013-2015) and financial support for BS, EA, and HM.

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Authors and Affiliations

  1. Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), CNRS UMR 8251, F-75205, Paris, France

    Jacqueline London, Claude Rouch, Linh Chi Bui, Elodie Assayag, Benoit Souchet, Fabrice Daubigney, Hind Medjaoui, Serge Luquet, Christophe Magnan, Jean Maurice Delabar, Julien Dairou & Nathalie Janel

  2. UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France

    Jean Maurice Delabar

  3. UMR 8601 CNRS, Université Paris Descartes, Paris Sorbonne Cité, 75270, Paris, France

    Julien Dairou

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  1. Jacqueline London
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Contributions

CR, JD, JL designed the study; CR, JD, JL, LCB, performed the HPLC experiments; CR, BS, EA, FD, HM, JL performed the other experiments; CR, EA, JD, JL JMD, LCB analyzed the data; JL and CR wrote the paper. CM, JD, NJ and SL correct the manuscript.

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Correspondence to Jacqueline London.

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The authors declare that the research was performed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors state no actual or potential conflict of interest.

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London, J., Rouch, C., Bui, L.C. et al. Overexpression of the DYRK1A Gene (Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A) Induces Alterations of the Serotoninergic and Dopaminergic Processing in Murine Brain Tissues. Mol Neurobiol 55, 3822–3831 (2018). https://doi.org/10.1007/s12035-017-0591-6

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