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P1‐100: Neuronal loss is age‐related and is not linked to massive neurofibrillary degeneration induced by expression of human truncated Tau protein in transgenic animals
Author(s) -
Koson Peter,
Zilka Norbert,
Korenova Miroslava,
Novak Michal
Publication year - 2008
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.2008.05.686
Subject(s) - tauopathy , nissl body , transgene , genetically modified mouse , tau protein , biology , spinal cord , pathology , neuron , neuroscience , neurodegeneration , medicine , alzheimer's disease , genetics , gene , disease , staining
GLT-1 dysfunction contributes to AD-related cognitive decline. Therefore, the objective of this study was to determine the consequences of reducing GLT-1 expression in a novel animal model of AD. Methods: To investigate this we crossed mice lacking one allele for GLT-1( /-) with APPswe/ PS1deltaE9 transgenic mice generating four experimental groups: APPswe/PS1deltaE9/GLT-1( / ); APPswe/PS1deltaE9/GLT-1( /-); nontransgenic GLT-1( / ); and non-transgenic GLT-1( /-). Using the Morris water maze we tested male mice aged to 6 months. Animals trained three days with a visible escape platform (training phase) followed with five testing days with a submerged (hidden) platform (testing phase). On the final test day a probe trial was performed (platform removed). Results: Across the three consecutive days of training all groups showed a significant reduction (p 0.001) in the latency to find the exposed platform that was statistically indistinguishable between groups. In the testing phase there was a statistically significant difference between groups (p 0.01) that was accounted for by the APPswe/PS1deltaE9/GLT-1( /-) mice which took significantly longer to find the hidden platform in comparison to the other groups (p 0.002). Additionally, the probe trial on the fifth day of testing showed that the APPswe/PS1deltaE9/GLT-1( /-) mice displayed no preference for the target quadrant and had significantly fewer entries into the target quadrant when compared to the other groups (p 0.01). Conclusions: Our findings show that partial loss of GLT-1 exacerbates the behavioral disturbances observed in transgenic mice expressing mutant APP and PS1, suggesting that GLT-1 dysfunction may contribute to cognitive decline in AD.