Influence of Transgenic Metallothionein-1 on Gliosis, CA1 Neuronal Loss, and Brain Metal Levels of the Tg2576 Mouse Model of Alzheimer’s Disease

International Journal of Molecular Sciences

Juan Hidalgo¹  Gemma Comes¹  Anna Escrig¹  Javier Carrasco¹  Paula Sanchis¹  Mercedes Giralt¹  Yasmina Manso¹  Amalia Molinero¹  Olaya Fernandez-Gayol¹ 

[1] Department of Cellular Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain;

关键词: Alzheimer’s disease;    Tg2576;    metallothionein-1;    amyloid plaques;    gliosis;    CA1 neuronal loss;    metals;   

DOI  :  10.3390/ijms18020251

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown