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Effects of Fibrillar Aβ 1–40 on the Viability of primary Cultures of Cholinergic Neurons and the Expression of Insulin Signaling–Related Proteins
Author(s) -
Du YiFeng,
Yan Peng,
Guo ShouGang,
Qu ChuanQiang
Publication year - 2011
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.21088
Subject(s) - irs1 , insulin receptor , viability assay , biology , microbiology and biotechnology , cholinergic neuron , cholinergic , signal transduction , insulin , cyclin dependent kinase 5 , western blot , apoptosis , endocrinology , protein kinase c , biochemistry , insulin resistance , gene , mitogen activated protein kinase kinase
To investigate the effects of fibrillar Aβ 1–40 on the morphology and viability of cholinergic neurons and the involvement of the insulin‐signaling pathway, we established primary cultures of rat basal forebrain cholinergic neurons and observed their responses to treatment with fibrillar Aβ 1–40 at different concentrations for different durations. Cell morphology was examined under microscope after immunofluorescence staining for neurofilament protein, cell vitality accessed by the Methyl thiazolyl tetrazolium assay, and expressions of a panel of insulin signaling–related proteins was detected by Western blot analysis. We show here that, at low concentrations of 0.1–1.0 μmol/L, fibrillar Aβ 1–40 had little effects on the cells; however, at higher concentrations of 2–10 μmol/L, it caused pathological changes, decreased the cell viability, and reduced the expression of insulin receptor, insulin receptor substrate‐I, Protein Kinase B, and B cell lymphoma/leukemia‐2 in a dose‐ and time‐dependent manner. These results demonstrate that fibrillar Aβ 1–40 not only decreases the viability of cholinergic neuron but also down regulates the expression of important proteins in the insulin signal transduction pathway. We speculate that fibrillar Aβ 1–40 may contribute to the pathogenesis of Alzheimer's through disrupting the insulin signaling pathway, therefore decreasing neuronal activity and eventually leading to the apoptosis and cell loss. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.