001     136446
005     20240614160202.0
024 7 _ |a 10.1016/j.bios.2011.12.026
|2 doi
024 7 _ |a pmid:22221799
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024 7 _ |a 0956-5663
|2 ISSN
024 7 _ |a 1873-4235
|2 ISSN
037 _ _ |a DZNE-2020-02768
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Jahnke, Heinz-Georg
|b 0
245 _ _ |a Impedance spectroscopy based measurement system for quantitative and label-free real-time monitoring of tauopathy in hippocampal slice cultures.
260 _ _ |a Amsterdam [u.a.]
|c 2012
|b Elsevier Science
264 _ 1 |3 print
|2 Crossref
|b Elsevier BV
|c 2012-02-01
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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542 _ _ |i 2012-02-01
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650 _ 7 |a Carbazoles
|2 NLM Chemicals
650 _ 7 |a Enzyme Inhibitors
|2 NLM Chemicals
650 _ 7 |a SRN 003-556
|2 NLM Chemicals
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Biosensing Techniques: instrumentation
|2 MeSH
650 _ 2 |a Carbazoles: pharmacology
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a Dielectric Spectroscopy: instrumentation
|2 MeSH
650 _ 2 |a Enzyme Inhibitors: pharmacology
|2 MeSH
650 _ 2 |a Equipment Design
|2 MeSH
650 _ 2 |a Hippocampus: cytology
|2 MeSH
650 _ 2 |a Neurites: drug effects
|2 MeSH
650 _ 2 |a Neurites: pathology
|2 MeSH
650 _ 2 |a Rats
|2 MeSH
650 _ 2 |a Rats, Sprague-Dawley
|2 MeSH
650 _ 2 |a Tauopathies: drug therapy
|2 MeSH
650 _ 2 |a Tauopathies: pathology
|2 MeSH
650 _ 2 |a tau Proteins: antagonists & inhibitors
|2 MeSH
700 1 _ |a Braesigk, Annett
|b 1
700 1 _ |a Mack, Till G A
|0 P:(DE-2719)9000424
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700 1 _ |a Pönick, Sarah
|b 3
700 1 _ |a Striggow, Frank
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700 1 _ |a Robitzki, Andrea A
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773 1 8 |a 10.1016/j.bios.2011.12.026
|b : Elsevier BV, 2012-02-01
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|t Biosensors and Bioelectronics
|v 32
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773 _ _ |a 10.1016/j.bios.2011.12.026
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