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P2–017: Inhibition of protein phosphatases induces impairment in axonal transport and spatial memory retention
Author(s) -
Yang Xifei,
Yang Ying,
Tian Qin,
Wang Xiaochuan,
Wang Qun,
Wang Jianzhi,
Li Geng,
Yang E.S.
Publication year - 2006
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.2006.05.854
Subject(s) - hyperphosphorylation , neurofilament , axoplasmic transport , phosphatase , hippocampus , cytoskeleton , microbiology and biotechnology , neuroscience , hippocampal formation , chemistry , morris water navigation task , tau protein , western blot , biology , phosphorylation , alzheimer's disease , biochemistry , medicine , immunohistochemistry , immunology , cell , disease , gene
Background: Abnormal accumulations of hyperphosphorylated neurofilaments (NFs) are seen in Alzheimer’s disease (AD). The in vitro studies have demonstrated that protein phosphatase-2A (PP-2A) and protein phosphatase-1 (PP-1) are two promising phosphatases responsible for Alzheimer-like NFs hyperphosphorylation. Objectives and Methods: To investigate the role of PP-2A and PP-1 in neurofilament hyperphosphorylation in vivo, we injected bilaterally calyculin A (CA), a selective inhibitor of PP-2A and PP-1 into hippocampus of rat brain. We found that CA-injected rats developed lesions in spatial memory retention in Morris water maze test. At mean time, NFs were hyperphosphorylated. To investigate the potential mechanism of memory lesions, we used a time-lapse imaging system to study the axonal transport by transitory transfection of GFP-neurofilament into N2a calls. We have found that CA significantly impairs the slowing axonal transport rate of neurofilament. At the same time, hyperphosphorylation of NFs are detected by Western blot. Conclusions: It is suggested from these data (i) that suppression of PP-2A and PP-1 is not only involved in the hyperphosphorylation of cytoskeletal proteins but also the damage in axonal transport of NFs; (ii) that the deficient axonal transport induced by PP-2A and PP-1 suppression in N2a cells may lead to accumulation of the hyperphosphorylated cytoskeletal proteins and thus impair the synaptic profiles and memory retention.