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

NEUROBIOLOGY OF DISEASE

卷:105

Article

Dekker, Alain D.^1,2,3,4,5  Vermeiren, Yannick^1,2,3  Albac, Christelle^4,5  Lana-Elola, Eva⁶  Watson-Scales, Sheona⁶  Gibbins, Dorota⁶  Aerts, Tony³  Van Dam, Debby^1,2,3  Fisher, Elizabeth M. C.⁷  Tybulewicz, Victor L. J.^6,8  Potier, Marie-Claude^4,5  De Deyn, Peter P.^1,2,3 

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Alzheimer Res Ctr, Hanzepl 1, NL-9713 GZ Groningen, Netherlands

[3] Univ Antwerp, Inst Born Bunge, Lab Neurochem & Behav, Univ Pl 1, B-2610 Antwerp, Belgium

[4] UPMC Univ Paris 06, Sorbonne Univ, CNRS, INSERM,U75,U1127,U7225, Blvd Hop, F-75013 Paris, France

[5] Inst Cerveau & Moelle Epiniere ICM, Blvd Hop, F-75013 Paris, France

[6] Francis Crick Inst, Midland Rd, London NW1 1AT, England

[7] UCL, Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London WC1N 3BG, England

[8] Imperial Coll London, Dept Med, Du Cane Rd, London W12 0NN, England

关键词: Aging;    Dopamine;    Down syndrome;    Dp1Tyb;    Monoamines;    Mouse models;    Noradrenaline;    RP-HPLC;    Serotonin;    Ts65Dn;   

DOI  :  10.1016/j.nbd.2017.06.007

来源: Elsevier

【 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 litter mates 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. (C) 2017 The Authors. Published by Elsevier Inc.

【 授权许可】

Free