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P4‐019: PHOSPHORYLATION OF TDP‐43 BY CASEIN KINASE 1 DELTA FACILITATES MISLOCALIZATION AND INTRACELLULAR AGGREGATE FORMATION OF TDP‐43
Author(s) -
aka Takashi,
Masai Hisao,
Hasegawa Masato
Publication year - 2014
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.2014.05.1533
Subject(s) - casein kinase 1 , phosphorylation , casein kinase 2 , kinase , cytoplasm , intracellular , microbiology and biotechnology , protein kinase a , biology , chemistry , ubiquitin , cyclin dependent kinase 2 , biochemistry , gene
Background: Tauopathy in entorhinal cortex (EC) starts early in Alzheimer’s disease (AD) and spreads anatomically to hippocampal formation. However, the mechanisms and the functional outcomes of the AD pathology initiating in the EC are unclear. Methods: We injected rAAV-CAG-GFP, rAAV-CAG-GFP-wtTAU or rAAV-CAG-GFP-P301L-TAU bilaterally into the medium entorhinal cortex (MEC) of male wild-type C57BL/6 mice aged 6 weeks. After 4 weeks, we used Morris water maze and in vitro long-term potentiation (LTP) recording to test spatial learning and memory and synaptic plasticity, respectively.Results: Four weeks after the injection, robust expression of AAV was confirmed by detecting green fluorescence specifically in MEC. Compared with mice injected with green fluorescent protein vector, P301L-Tau group showed severe spatial memory deficit 4 weeks after injection, whereas wtTau group was not affected on the water maze task. In vitro electrophysiology indicated LTP were impaired in both P301L-Tau group and wtTau group. At 3m and 6m after the injection, the mice expressing wtTau also showed memory deficits. Conclusions: P301L-Tau and wt-Tau induce respectively acute and chronic behavioral impairments; AAV-induced tau expression in EC is sufficient to establish a preclinical model for understanding the development and functional outcomes of tauopathy in AD.