84bc7442e2380489ec203e9583a40211 pmc_28134760.pdf 3ec494dc0da1fe9b95dc46425944ddbb290f9006 pmc_28134760.pdf 9787d7a0430e55e5fc4f2e24f796a95a938da5b2da4f6d6ddd4ef96a001518c8 pmc_28134760.pdf Title: Influence of Transgenic Metallothionein-1 on Gliosis, CA1 Neuronal Loss, and Brain Metal Levels of the Tg2576 Mouse Model of Alzheimer’s Disease Subject: The mouse model of Alzheimer’s disease (AD), Tg2576 mice (APP), has provided valuable information, such as the role of the metallothionein (MT) family in their behavioral and amyloidosis phenotypes. In this study, we further characterize the role of MT-1 by crossing Mt1-overexpressing mice with Tg2576 mice (APPTgMT). In 14-month-old mice, MT-1(/2) protein levels were dramatically increased by Mt1 overexpression throughout the cortex (Cx), which showed a prominent caudal-rostral gradient, and the hippocampus (HC). There was a trend for MT-1(/2) immunostaining to be increased in the areas surrounding the amyloid plaques in control male mice but not in Mt1-overexpressing mice. Gliosis was elicited by the amyloid plaques, but the effects of Mt1 overexpression were modest. However, in hippocampal western blots the microglial marker Iba-1 was increased in old male APPTgMT mice compared to APP-wild type (APPWT) mice, and the opposite was observed in young mice. Hippocampal CA1 neuronal loss was observed in Tg2576 mice, but was unaffected by Mt1 overexpression. Aging increased Zn and Cu levels differently depending on brain area, sex, and genotype. Thus, the effects of Mt1 overexpression on the phenotype of Tg2576 mice here studied are modest. Keywords: Alzheimer’s disease; Tg2576; metallothionein-1; amyloid plaques; gliosis; CA1 neuronal loss; metals Author: Gemma Comes, Yasmina Manso, Anna Escrig, Olaya Fernandez-Gayol, Paula Sanchis, Amalia Molinero, Mercedes Giralt, Javier Carrasco and Juan Hidalgo Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.17 CreationDate: Thu Jan 26 07:46:03 2017 CET ModDate: Thu Jan 26 07:46:03 2017 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 5810079 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- EDXWVB+URWPalladioL-Ital Type 1 Custom yes yes no 80 0 JNTDAU+URWPalladioL-Bold Type 1 Custom yes yes no 81 0 TKESWR+URWPalladioL-Roma Type 1 Custom yes yes no 82 0 VVSYYB+EURM10 Type 1 Builtin yes yes no 83 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C 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