Proteomic analysis of six- and twelve-month hippocampus and cerebellum in a murine Down syndrome model

NEUROBIOLOGY OF AGING

卷:63

Article

Vacano, Guido N.^1,2  Gibson, David S.^3,5  Turjoman, Abdullah Arif^3,6  Gawryluk, Jeremy W.^4,7  Geiger, Jonathan D.⁴  Duncan, Mark^3,8  Patterson, David^1,2 

[1] Univ Denver, Eleanor Roosevelt Inst, Knoebel Inst Hlth Aging, Denver, CO USA

[2] Univ Denver, Dept Biol Sci, 2155 E Wesley Ave, Denver, CO 80208 USA

[3] Univ Colorado, Denver Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO USA

[4] Univ North Dakota, Sch Med & Hlth Sci, Dept Biomed Sci, Grand Forks, ND 58201 USA

[5] Univ Ulster, Biomed Sci Res Inst, Northern Ireland Ctr Stratified Med, Altnagelvin Area Hosp, C TRIC Bldg,Glenshane Rd, Coleraine, Londonderry, North Ireland

[6] Prince Mohammed Bin Abdulaziz Hosp, Riyadh, Saudi Arabia

[7] Univ British Columbia, Mitacs Inc, Technol Enterprise Facil, Vancouver, BC, Canada

[8] Biodesix Inc, Boulder, CO USA

关键词: Aging;    Down syndrome;    Alzheimer's disease;    Ts65Dn;    Brain;    Proteome;   

DOI  :  10.1016/j.neurobiolaging.2017.11.010

来源: Elsevier

【 摘 要 】

This study was designed to investigate the brain proteome of the Ts65Dn mouse model of Down syndrome. We profiled the cerebellum and hippocampus proteomes of 6- and 12-month-old trisomic and disomic mice by difference gel electrophoresis. We quantified levels of 2082 protein spots and identified 272 (170 unique UniProt accessions) bymass spectrometry. Four identified proteins are encoded by genes trisomic in the Ts65Dn mouse. Three of these (CRYZL11, EZR, and SOD1) were elevated with p-value < 0.05, and 2 proteins encoded by disomic genes (MAPRE3 and PHB) were reduced. Intergel comparisons based on age (6 vs. 12 months) and brain region (cerebellum vs. hippocampus) revealed numerous differences. Specifically, 132 identified proteins were different between age groups, and 141 identified proteins were different between the 2 brain regions. Our results suggest that compensatory mechanisms exist, which ameliorate the effect of trisomy in the Ts65Dn mice. Differences observed during aging may play a role in the accelerated deterioration of learning and memory seen in Ts65Dn mice. (C) 2017 Elsevier Inc. All rights reserved.

【 授权许可】

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