title: Effects of fibrillar Aβ(1-40) on the viability of primary cultures of cholinergic neurons and the expression of insulin signaling-related proteins.
abstract: 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 micromol/L, fibrillar Aβ(1-40) had little effects on the cells; however, at higher concentrations of 2-10 μmicromol/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.
authors.affiliation: Department of Neurology, Shandong University Affiliated Provincial Hospital, Jinan, Shangdong 250021, China.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Du
authors.forename: Peng
authors.initials: P
authors.lastname: Yan
authors.forename: Shou-Gang
authors.initials: SG
authors.lastname: Guo
authors.forename: Chuan-Qiang
authors.initials: CQ
authors.lastname: Qu
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D023421:Models, Animal; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; C078592:amyloid beta-protein (1-40); D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt