Journal
NEUROBIOLOGY OF DISEASE
Volume 105, Issue -, Pages 235-244Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2017.06.007
Keywords
Aging; Dopamine; Down syndrome; Dp1Tyb; Monoamines; Mouse models; Noradrenaline; RP-HPLC; Serotonin; Ts65Dn
Categories
Funding
- Alzheimer Research Center of the University Medical Center Groningen (UMCG)
- Research School for Behavioural and Cognitive Neurosciences of the University of Groningen (RUG)
- Gratama-Stichting/Stichting Groninger Universiteitsfonds [2015-04]
- Interuniversity Poles of Attraction (IAP Network) of the Belgian Federal Science Policy Office [P7/16]
- Belgian Foundation for Alzheimer Research (SAO-FRA) [15002]
- Institute Born-Bunge
- University of Antwerp
- French Ministry of Health [PHRC-0054-N 2013]
- Wellcome Trust [098327, 098328]
- AnEUploidy integrated project (EU Framework 6)
- MRC [U117527252]
- Francis Crick Institute [FC001194]
- MRC
- Cancer Research UK
- Wellcome Trust
- Wellcome Trust [098327/Z/12/Z] Funding Source: Wellcome Trust
- Alzheimer's Society [192] Funding Source: researchfish
- Medical Research Council [G0601056] Funding Source: researchfish
- The Francis Crick Institute [10197] Funding Source: researchfish
- Wellcome Trust [098327/Z/12/Z] Funding Source: researchfish
- MRC [G0601056] Funding Source: UKRI
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available