Aging rather than aneuploidy affects monoamine neurotransmitters in brain regions of Down syndrome mouse models

Neurobiology of Disease

Sheona Watson-Scales¹  Peter P. De Deyn¹  Yannick Vermeiren¹  Christelle Albac²  Eva Lana-Elola³  Alain D. Dekker³  Marie-Claude Potier³  Victor L.J. Tybulewicz⁴  Dorota Gibbins⁵  Tony Aerts⁶  Elizabeth M.C. Fisher⁶  Debby Van Dam⁶ 

[1] Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium;Sorbonne Universités, UPMC Université Paris 06, INSERM, CNRS (U75, U1127, U7225) and Institut du Cerveau et de la Moelle Epinière (ICM), Boulevard de l'Hôpital, 75013 Paris, France;Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium;Sorbonne Universités, UPMC Université Paris 06, INSERM, CNRS (U75, U1127, U7225) and Institut du Cerveau et de la Moelle Epinière (ICM), Boulevard de l'Hôpital, 75013 Paris, France;The Francis Crick Institute, Midland Road, London NW1 1AT, United Kingdom;

关键词: Aging;    Dopamine;    Down syndrome;    Dp1Tyb;    Monoamines;    Mouse models;   

DOI  :  

来源: DOAJ

【 摘 要 】

Altered concentrations of monoamine neurotransmitters and metabolites have been repeatedly found in people with Down syndrome (DS, trisomy 21). Because of the limited availability of human post-mortem tissue, DS mouse models are of great interest to study these changes and the underlying neurobiological mechanisms. Although previous studies have shown the potential of Ts65Dn mice – the most widely used mouse model of DS – to model noradrenergic changes, a comprehensive monoaminergic characterization in multiple brain regions has not been performed so far. Here, we used RP-HPLC with electrochemical detection to quantify (nor)adrenergic (NA, adrenaline and MHPG), dopaminergic (DA, HVA and DOPAC), and serotonergic compounds (tryptophan, 5-HT and 5-HIAA) in ten regionally dissected brain regions of Ts65Dn mice, as well as in Dp1Tyb mice – a novel DS mouse model. Comparing young adult aneuploid mice (2.5–5.5 months) with their euploid WT littermates did not reveal generalized monoaminergic dysregulation, indicating that the genetic overload in these mice barely affected the absolute concentrations at this age. Moreover, we studied the effect of aging in Ts65Dn mice: comparing aged animals (12–13 months) with their younger counterparts revealed a large number of significant changes. In general, the (nor)adrenergic system appeared to be reduced, while serotonergic compounds were increased with aging. Dopaminergic alterations were less consistent. These overall patterns appeared to be relatively similar for Ts65Dn and WT mice, though more observed changes were regarded significant for WT mice. Similar human post-mortem studies are necessary to validate the monoaminergic construct validity of the Ts65Dn and Dp1Typ mouse models.

【 授权许可】

Unknown