Upregulation of the neuronal Per-Arnt-Sim domain protein 4 (Npas4) in the rat corticolimbic system following focal cerebral ischemia

Eur J Neurosci. 2013 Jun;37(11):1875-84. doi: 10.1111/ejn.12163. Epub 2013 Feb 22.

Abstract

The neuronal Per-Arnt-Sim domain protein 4 (Npas4) is an important transcriptional regulator of synaptic plasticity and cognition. The present study characterises the in vivo neuroanatomical expression pattern of the Npas4 protein in a rat model of focal cerebral ischemia. Animals were subjected to unilateral middle cerebral artery occlusion for 2 h, after which the spatiotemporal and neuronal profiles of Npas4 protein expression were analysed by immunohistochemistry at different time points post-reperfusion. Focal cerebral ischemia induced an early, transient and robust upregulation of Npas4 in a brain region-dependent manner involving predominantly principal neurons. Interestingly, we observed a unique differential induction of Npas4 protein expression in corticolimbic regions of the rat brain that are critically linked to cognition and emotion. These findings suggest that stroke-induced Npas4 upregulation may be involved in a transcriptional regulatory program within the corticolimbic circuitry following an ischemic insult.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Infarction, Middle Cerebral Artery / metabolism*
  • Limbic System / metabolism*
  • Limbic System / pathology
  • Male
  • Neurons / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Npas4 protein, rat