TY  - JOUR
AU  - Jahnke, Heinz-Georg
AU  - Braesigk, Annett
AU  - Mack, Till G A
AU  - Pönick, Sarah
AU  - Striggow, Frank
AU  - Robitzki, Andrea A
TI  - Impedance spectroscopy based measurement system for quantitative and label-free real-time monitoring of tauopathy in hippocampal slice cultures.
JO  - Biosensors and bioelectronics
VL  - 32
IS  - 1
SN  - 0956-5663
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2020-02768
SP  - 250-258
PY  - 2012
AB  - 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.
KW  - Animals
KW  - Biosensing Techniques: instrumentation
KW  - Carbazoles: pharmacology
KW  - Cells, Cultured
KW  - Dielectric Spectroscopy: instrumentation
KW  - Enzyme Inhibitors: pharmacology
KW  - Equipment Design
KW  - Hippocampus: cytology
KW  - Neurites: drug effects
KW  - Neurites: pathology
KW  - Rats
KW  - Rats, Sprague-Dawley
KW  - Tauopathies: drug therapy
KW  - Tauopathies: pathology
KW  - tau Proteins: antagonists & inhibitors
KW  - Carbazoles (NLM Chemicals)
KW  - Enzyme Inhibitors (NLM Chemicals)
KW  - SRN 003-556 (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:22221799
DO  - DOI:10.1016/j.bios.2011.12.026
UR  - https://pub.dzne.de/record/136446
ER  -