• K Ishihara, S Kanai, H Sago, K Yamakawa, and S Akiba.
• Department of Pathological Biochemistry, Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan; Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan. Electronic address: ishihara@mb.kyoto-phu.ac.jp.
• Neuroscience. 2014 Dec 5; 281: 1-15.

AbstractTo identify molecular candidates involved in brain disabilities of Ts1Cje, a mouse model of Down syndrome (DS), we performed comparative proteomic analyses. Proteins extracted from the brains of postnatal wild-type (WT) and Ts1Cje mice were analyzed by two-dimensional gel electrophoresis (2-DE). No differences were detected in the proteins expressed in the whole brain between WT and Ts1Cje mice at postnatal day 0 and 3months of age. Five spots with differential expression in the brains of Ts1Cje mice were detected by 2-DE of brain proteins from WT and Ts1Cje embryos at embryonic day 14.5 (E14.5). These differentially expressed proteins in Ts1Cje embryos were identified as calcyclin-binding protein (CACYBP), nucleoside diphosphate kinase-B (NDPK-B), transketolase (TK), pyruvate kinase (PK), and 60S acidic ribosomal protein P0 (RPLP0) by peptide mass fingerprinting. CACYBP and NDPK-B were involved in cell proliferation, whereas TK and PK were associated with energy metabolism. Experiments on cell proliferation, an in vivo bromodeoxyuridine (BrdU)-labeling experiment, and immunohistochemical analysis for phospho-histone H3 (an M-phase marker) demonstrated increased numbers of BrdU-positive and M-phase cells in the ganglionic eminence. Our findings suggest that the dysregulated expression of proteins demonstrated by comparative proteomic analysis could be a factor in increased cell proliferation, which may be associated with abnormalities in DS brain during embryonic life. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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