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Related Experiment Video

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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
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Published on: January 2, 2015

Propofol directly increases tau phosphorylation.

Robert A Whittington1, László Virág, François Marcouiller

  • 1Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America. raw9@columbia.edu

Plos One
|February 10, 2011
PubMed
Summary

Propofol, a common anesthetic, increases tau phosphorylation in the brain under normal temperatures, potentially impacting neurodegenerative diseases. This effect, linked to protein phosphatase 2A inhibition, was observed in mice and cell cultures.

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Area of Science:

  • Neuroscience
  • Biochemistry

Background:

  • Alzheimer's disease (AD) and tauopathies involve tau hyperphosphorylation and neurofibrillary pathology.
  • Anesthetics can induce tau hyperphosphorylation via hypothermia-related inhibition of protein phosphatase 2A (PP2A).

Purpose of the Study:

  • To investigate the effects of propofol on tau phosphorylation under normothermic conditions.
  • To explore the role of PP2A in propofol-induced tau hyperphosphorylation.

Main Methods:

  • Administered propofol (250 mg/kg i.p.) to mice and assessed tau phosphorylation at various epitopes in hippocampal and cortical tissues.
  • Examined tau phosphorylation in propofol-treated SH-SY5Y cells overexpressing human tau.
  • Measured PP2A activity and expression levels post-propofol administration.

Main Results:

  • Propofol significantly increased tau phosphorylation at multiple sites in mouse hippocampus and cortex under normothermia.
  • Tau hyperphosphorylation persisted for at least 2 hours post-propofol administration, with PP2A activity and expression initially decreasing.
  • In vitro, propofol exposure also led to tau hyperphosphorylation in SH-SY5Y cells.

Conclusions:

  • Propofol increases tau phosphorylation in vivo and in vitro under normothermic conditions.
  • PP2A inhibition is implicated in propofol-induced tau hyperphosphorylation.
  • Further research is needed to determine propofol's impact on neurofibrillary pathology progression.