title: A novel organotypic tauopathy model on a new microcavity chip for bioelectronic label-free and real time monitoring.
abstract: Herewith we developed a novel 3D in vitro Alzheimer's disease (AD) model, based on the human neuroblastoma cell line SH-SY5Y, which is well differentiated without the application of any agents. Furthermore AD-like pathological neurodegeneration can be induced by okadaic acid (OA) mediated hyperphosphorylation of the microtubule associated protein tau. Moreover, we established stable "rapid tauopathy cell lines" expressing additional EGFP-fused (enhanced green fluorescent protein) wildtype or a pathology-promoting mutant tau variant (P301L) by lentiviral transduction. For the sensitive and feasible quantitative detection of pathological effects on neuronal 3D-cultures by electrochemical impedance spectroscopy (EIS) we optimized and redesigned a microcavity array (MCA). The cellular contribution to impedance could be increased by the factor of 2.5 and the variance decreased by 40%. Using our optimized MCA and impedance measurement setup we were able to detect quantitatively an OA concentration- and time-dependent decrease of the impedance in 3D SH-SY5Y cultures. Moreover, we were able to detect and quantify distinct, AD-related effects triggered by tau-mutant (P301L) expression and hyperphosphorylation in our organotypic 3D-cultures with the help of impedance spectroscopy.
authors.affiliation: Centre for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Krinke
authors.forename: Heinz-Georg
authors.initials: HG
authors.lastname: Jahnke
authors.forename: Till G A
authors.initials: TG
authors.lastname: Mack
authors.forename: Anika
authors.initials: A
authors.lastname: Hirche
authors.forename: Frank
authors.initials: F
authors.lastname: Striggow
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Robitzki
mesh_terms: D001681:Biological Assay / Q000295:instrumentation*; D015374:Biosensing Techniques / Q000295:instrumentation*; D045744:Cell Line, Tumor; D003199:Computer Systems; D058266:Dielectric Spectroscopy / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D046228:Microarray Analysis / Q000295:instrumentation*; D008904:Miniaturization; D013194:Staining and Labeling; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins