Overexpression of the DYRK1A Gene (Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A) Induces Alterations of the Serotoninergic and Dopaminergic Processing in Murine Brain Tissues
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.
KeywordsTrisomy 21 (T21) DYRK1A mBACtgDyrk1a mice Brain tissues Monoamine neurotransmitters High-performance liquid chromatography with electrochemical detection (HPLC-ED)
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.
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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Conflict of Interest
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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