title: Aβ oligomers-induced toxicity is attenuated in cells cultured with NbActiv4™ medium.
abstract: Pathogenic Aβ-derived diffusible ligands (ADDLs) bind to post-synaptic targets, induce excessive reactive oxygen species (ROS) and stimulate tau hyperphosphorylation in cultured neurons. Recently, NbActiv4™ medium was reported to increase neuron synapse densities in cultured hippocampal neurons. We aimed to investigate the effect of this novel medium on ADDL-induced toxicity. We found that ADDL-induced ROS was attenuated in cells cultured with NbActiv4™. ADDL binding assay was performed in neurons cultured by different feeding conditions with NbActiv4™. Feeding cells with 30 % medium once a week, ADDL binding sites were abundant at days in vitro (DIV) 18. However, changing 50 % medium once a week decreased ADDL binding about 80 %. NbActiv4™ produced about 40 % more glial fibrillary acidic protein (GFAP) positive astrocytes than the widely used hippocampal culture medium, neurobasal supplemented with B27 (neurobasal/B27). Astrocytes are reported to produce kinds of trophic factors including insulin-like growth factor 1 (IGF-1). Consistently, when cultured with NbActiv4™, neurons were sensitive to inhibitors of insulin/IGF-1 signaling in response to ADDL attack. Overall, this study supports the important role of astrocytes in neuroprotection and indicates that targeting astrocytes dysfunction may lead to new therapeutic strategies for Alzheimer's disease.
authors.affiliation: Northwestern University Interdepartmental Neuroscience Program, 320 East Superior St., Searle 5-474, Chicago, IL 60611, USA. yzhou@u.northwestern.edu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: William L
authors.initials: WL
authors.lastname: Klein
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology; D003401:Creatine / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors; D004967:Estrogens / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002148:Calmodulin-Binding Proteins; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D004967:Estrogens; D005904:Glial Fibrillary Acidic Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D002784:Cholesterol; D003401:Creatine