Age exacerbates abnormal protein expression in a mouse model of Down syndrome.

Autor: Ahmed MM; Linda Crnic Institute for Down Syndrome, Aurora, CO, USA., Block A; Linda Crnic Institute for Down Syndrome, Aurora, CO, USA., Tong S; School of Public Health, University of Colorado Denver School of Medicine, Aurora, CO, USA., Davisson MT; The Jackson Laboratory, Bar Harbor, ME, USA., Gardiner KJ; Linda Crnic Institute for Down Syndrome, Aurora, CO, USA; Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, CO, USA; Human Medical Genetics and Genomics, and Neuroscience Programs, University of Colorado Denver School of Medicine, Aurora, CO, USA. Electronic address: Katheleen.gardiner@ucdenver.edu.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2017 Sep; Vol. 57, pp. 120-132. Date of Electronic Publication: 2017 May 10.
DOI: 10.1016/j.neurobiolaging.2017.05.002
Abstrakt: The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at ∼6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer's disease. Among brain regions, the number of abnormalities in cerebellum decreased while the number in cortex greatly increased with age. The Ts65Dn is being used in preclinical evaluations of drugs for cognition in DS. Most commonly, drug evaluations are tested in ∼4- to 6-month-old mice. Data on age-related changes in magnitude and specificity of protein perturbations can be used to understand the molecular basis of changes in cognitive ability and to predict potential age-related specificities in drug efficacies.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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