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P4‐202: Activation of MT2 receptor rescues Alzheimer‐like axonopathy and promotes axon outgrowth
Author(s) -
Liu Dan,
Zhu LingQiang,
Wang JianZhi
Publication year - 2009
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.2009.04.668
Subject(s) - axon , wortmannin , receptor , hippocampal formation , axon terminal , neuroscience , microbiology and biotechnology , chemistry , signal transduction , biology , pi3k/akt/mtor pathway , biochemistry
Background: Axonopathy is the most prominent pathological changes in Alzheimer’s disease. However, the underlying mechanism of axonopathy is unclear now. MT2 receptor (MT2R) is the second subtype of melatonin membrane receptor, which is G-protein coupled receptor and coupling with multiple signal transduction cascades. Recently, a lot of works reported that the expression of MT2R is decreased in Alzheimer’s disease. But the direct link of MT2R to axonopathy in AD is still unknown. Methods: Primary hippocampal neurons were cultured from E18 rats. Transfection of Wild type GSK-3 plasmid and treatment of wortmannin were used to mimic the axonopathy in AD. Double-labeled immunofluorescence with specific axonal marker, Tau1 and specific dendritic marker, MAP2 were performed. FM4-64 releasing is to evaluate the axon function. Image J calculation was applied for analysis. Results: MT2R agonists (melatonin, IIK7) can rescue the axon outgrowth inhibition induced by overexpression of wild type GSK-3 and treatment of wortmannin. Additionally, MT2R agonists treatment promote the axon outgrowth at both the establishment stage and the maintenance stage of neuronal polarity, The ratio of multiple-axons is increased to 58% and the ‘‘extra’’ axons also preserve the normal vesicle recycling function. However, the MT2R antagonists (luzindole, K185) has contrary functions. Conclusions: Activation of MT2 receptor can rescue AD like axonopathy and promote the axon outgrowth in hippocampus neurons.