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

This study was designed to investigate the brain proteome of the Ts65Dn mouse model of Downsyndrome. We profiled the cerebellum and hippocampus proteomes of six and twelve-month-old trisomic and disomic mice by Difference Gel Electrophoresis. We quantified levels of 2082 protein spots and identified 272 (170 unique UniProt accessions) by mass 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 two proteins encoded by disomic genes (MAPRE3 and PHB) were reduced. Inter-gel comparisons based on age (six versus twelve-month) and brain region (cerebellum versus hippocampus) revealed numerous differences. Specifically, 132 identified proteins were different between age groups, and 141 identified proteins weredifferent between the two 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.