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P4‐039: Differences between TG2576‐ and APP/PS1 Mice in High‐Throughput Behavioral Screening Correlates with Differences in Brain Pathology
Author(s) -
Hanania Taleen,
Havas Daniel,
Sabath Emily,
Kabitzke Patricia,
Mazella Matthew,
Cox Kimberly,
Berger Jason,
Windisch Manfred,
Brunner Daniela,
Alexandrov Vadim
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.2128
Subject(s) - mouse strain , phenotype , immunohistochemistry , pathology , cognition , psychology , immune system , animal model , neuroscience , medicine , biology , immunology , genetics , gene
The APP/PS1 double transgenic mice were created by cross between Tg2576 (APP695sw) and a mutant PS1 (M146L) mouse line (Holcomb et al 1998; 1999). These mice show increased amyloid-β 40 and 42 levels and develop early amyloid pathology in the cerebral cortex and hippocampus, accompanied by signs of neuro-inflammation (Jimenez et al., 2008), characterized by significant microglia activation and significant astrogliosis in cortex and hippocampus. The mice also show increased brain and peripheral inflammatory markers. Behavioral deficits correlate to brain pathology (Gordon et al., 2001), resulting in a significant memory deficit as early as 12 weeks of age in spontaneous alternation, fear conditioning and spatial learning. This behavioral abnormality seems to persist at later ages (6 to 9 months). Spatial reference memory as measured by Morris water maze is altered around 5-6 months of age (Gong et al., 2004). Also, sensorimotor functions, including hearing vestibular functions and motor coordination, are intact in the APP/PS1 mice (Holcomb et al., 1999).