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Intermittent hypoxia regulates RNA polymerase II in hippocampus and prefrontal cortex

M L Ignacak1, S V Harbaugh, E Dayyat

  • 1Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati, OH 45267-0505, USA.

Neuroscience
|December 20, 2008
PubMed

Insights

Intermittent hypoxia (IH) causes specific RNA polymerase II modifications in brain regions linked to cognitive deficits. These changes, not seen with sustained hypoxia (SH), may underlie neural dysfunction in sleep-disordered breathing.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Sleep Medicine

Background:

  • Intermittent hypoxia (IH) is a key factor in neural deficits seen in sleep-disordered breathing.
  • Understanding the molecular mechanisms behind IH-induced neural damage is crucial.

Purpose of the Study:

  • To investigate the effects of IH on posttranslational modifications of RNA polymerase II subunit Rpb1 in specific brain regions.
  • To determine if these modifications correlate with cognitive deficits induced by IH.
  • To explore the role of the von Hippel-Lindau protein in IH-induced Rpb1 modifications.

Main Methods:

  • Exposure of mice to IH or sustained hypoxia (SH) for 2 or 30 days.
  • Analysis of Rpb1 posttranslational modifications (hydroxylation, phosphorylation, ubiquitylation) in distinct brain regions (hippocampal CA1, prefrontal cortex).
  • Behavioral assays to assess cognitive function in exposed mice.
  • In vitro studies using PC12 cells to examine the role of the von Hippel-Lindau protein.

Main Results:

  • IH, but not SH, induced Rpb1 hydroxylation, phosphorylation, and ubiquitylation in hippocampal CA1 and prefrontal cortex.
  • Mice exposed to IH for 14 or 30 days exhibited cognitive deficits.
  • The von Hippel-Lindau protein was required for IH-induced Rpb1 modifications in PC12 cells.

Conclusions:

  • Chronic intermittent hypoxia induces specific Rpb1 posttranslational modifications in brain regions critical for cognition.
  • These modifications are associated with cognitive deficits observed in IH.
  • Rpb1 modifications may play a role in regulating gene expression contributing to IH-induced neural dysfunction.

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