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

Dekker, AD; Vermeiren, Y; Albac, C; Lana-Elola, E; Watson-Scales, S; Gibbins, D; Aerts, T; ... De Deyn, PP; + view all (2017) Aging rather than aneuploidy affects monoamine neurotransmitters in brain regions of Down syndrome mouse models. Neurobiology of Disease , 105 pp. 235-244. 10.1016/j.nbd.2017.06.007. Green open access

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Abstract

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 (2.5-5.5months) 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 (12-13months) 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.

Type: Article
Title: Aging rather than aneuploidy affects monoamine neurotransmitters in brain regions of Down syndrome mouse models
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.nbd.2017.06.007
Publisher version: http://doi.org/10.1016/j.nbd.2017.06.007
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Aging, Dopamine, Down syndrome, Dp1Tyb, Monoamines, Mouse models, Noradrenaline, RP-HPLC, Serotonin, Ts65Dn
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1561227
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