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P4‐208: Intranasal insulin prevents anesthesia‐induced spatial memory deficit in mice
Author(s) -
Dai Chunling,
Zhang Yongli,
Liu Fei,
Iqbal Khalid,
Gong Cheng-Xin
Publication year - 2015
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.2015.08.036
Subject(s) - postoperative cognitive dysfunction , hyperphosphorylation , sevoflurane , medicine , morris water navigation task , nasal administration , anesthesia , cognitive deficit , cognitive decline , insulin , synaptophysin , memantine , cognition , pharmacology , hippocampus , dementia , disease , cognitive impairment , biology , kinase , psychiatry , immunohistochemistry , microbiology and biotechnology
determine whether Ab deposits induce endotoxin/TLR tolerance, lipopolysaccharide (LPS) was injected into the brains of AD-model and control mice at the age of 2 months (before Ab deposition) and 12 months (after Ab deposition) and activation levels of microglia in the brains were compared between the AD model and control groups by immunohistochemistry followed by morphometric analysis using antibodies against activated microglial markers (IBa1 and CD45). In order to investigate the molecular mechanisms of possible LPS/Ab tolerance in the AD model, expression levels of signaling molecules that are known to regulate TLR tolerance were determined by quantitative real-time PCR (qPCR). Results: Although LPS injection induced higher expression levels of the microglial markers in AD model mice than those in control mice at 2 months of age, expression levels of microglial markers in AD-model mice were lower than those in control mice after LPS injection at 12 months. Expression levels of TGF-b, A20, NF-kB p50, INPP5D, and miR-146a increased in 12 month-old but not 2-month-old AD model mice. These molecules inhibit TLR signaling. Conclusions: The results suggest that Ab deposition induces LPS tolerance in microglia through upregulation of TLR4 signaling inhibitors. Such TLR4 signaling inhibitors can be therapeutic targets for AD.