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[P4–452]: SERUM/GLUCOCORTICOID REGULATED KINASE 1 (SGK1), TAU PATHOLOGY AND COGNITIVE DYSFUNCTION IN HIGH‐FAT‐DIET‐FED TAUOPATHY MODEL MICE
Author(s) -
Elahi Montasir,
Motoi Yumiko,
Ishiguro Koichi,
Hattori Nobutaka
Publication year - 2017
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.2017.07.613
Subject(s) - morris water navigation task , medicine , endocrinology , tauopathy , insulin tolerance test , genetically modified mouse , tau protein , glucocorticoid , protein kinase b , hippocampus , glucocorticoid receptor , corticosterone , insulin resistance , transgene , insulin , biology , alzheimer's disease , neurodegeneration , phosphorylation , hormone , disease , biochemistry , insulin sensitivity , gene
from 4 different groups of mice depending on the TBI paradigm and time point after TBI at which the brains were collected: 1) sacrificed at 24 hours after a 50 psi single blast treatment, 2) sacrificed at 3 weeks after a 50 psi single blast treatment, 3) sacrificed at 3 weeks after repeated blast treatment (6 blasts over two weeks), 4) sacrificed at 3 weeks following anesthesia (sham group). The isolated tau oligomers were analyzed biochemically via PK digestion, western blotting and seeding. Moreover, their toxicity, internalization and spreading were tested in cell culture. Results:Results show that the TBI brain-derived Tau samples resemble tau oligomeric strains in terms of PK digestion pattern and reactivity with tau oligomer monoclonal antibodies. In addition, some of the samples were found to be toxic, and express different internalization levels into SY5Y cells in culture. Conclusions: Results suggest that different TBI brain-derived Tau oligomeric-like strains contribute to the neuronal death observed after TBI. Future experiments will investigate the samples’ differential ability to induce cell toxicity and neurodegeneration in vitro and in vivo. Results hold substantial translational implications towards applying Tau-immunotherapy techniques to reduce the risk for late-life dementia.