Journal Article

DZNE-2020-02768

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Impedance spectroscopy based measurement system for quantitative and label-free real-time monitoring of tauopathy in hippocampal slice cultures.

Jahnke, H.-G. ; Braesigk, A. ; Mack, T. G. A.DZNE* ; Pönick, S. ; Striggow, F.DZNE* ; Robitzki, A. A. (Corresponding author)

2012
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.bios.2011.12.026

Abstract: Alzheimer's disease (AD) and other tauopathies comprise death of cell bodies, synapses and neurites but there is surprising little knowledge of the temporal sequence and the causal relationships among these events. Here, we present a novel biosensoric approach to monitor retrograde neurite degeneration before cell death occurs. We induced tau hyperphosphorylation in organotypic hippocampal slice cultures (OHSC) and applied marker-independent real-time electrical impedance spectroscopy (EIS) for cellular real-time pathology monitoring. Using this approach, we were able to define two distinct phases of neurite degeneration, first a rapid swelling of axonal processes that manifests itself in relative impedance above control levels followed by a slower phase of collapse and subsequent fragmentation indicated by decreased relative impedance below control levels. Initial axon swelling is strictly dose-dependent and swelling intensity correlates with second phase impedance decrease implicating a causative link between both degenerative mechanisms. Moreover, suppressing tau hyperphosphorylation by kinase inhibition nearly prevented both phases of axon degeneration. Our findings demonstrate that the temporal sequence of tau-triggered neurite degeneration can be directly visualized by EIS-based, non-invasive and label-free monitoring. We therefore suggest this approach as a powerful extension of high content applications to study mechanisms of neurite degeneration and to exploit therapeutic options against AD and tau-related disorders.

Keyword(s): Animals (MeSH) ; Biosensing Techniques: instrumentation (MeSH) ; Carbazoles: pharmacology (MeSH) ; Cells, Cultured (MeSH) ; Dielectric Spectroscopy: instrumentation (MeSH) ; Enzyme Inhibitors: pharmacology (MeSH) ; Equipment Design (MeSH) ; Hippocampus: cytology (MeSH) ; Neurites: drug effects (MeSH) ; Neurites: pathology (MeSH) ; Rats (MeSH) ; Rats, Sprague-Dawley (MeSH) ; Tauopathies: drug therapy (MeSH) ; Tauopathies: pathology (MeSH) ; tau Proteins: antagonists & inhibitors (MeSH) ; Carbazoles ; Enzyme Inhibitors ; SRN 003-556 ; tau Proteins

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Contributing Institute(s):

1. Neurodegeneration and Intervention Strategies (AG Striggow)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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