Neonatal stroke in mice causes long-term changes in neuronal notch-2 expression that may contribute to prolonged injury

Lavinia Albéri, Zhikai Chi, Shilpa D. Kadam, Justin D. Mulholland, Valina L. Dawson, Nicholas Gaiano, Anne M. Comi

Research output: Contribution to journalArticle

Abstract

BACKGROUND AND PURPOSE-: Notch receptors (1-4) are membrane proteins that, on ligand stilumation, release their cytoplasmic domains to serve as transcription factors. Notch-2 promotes proliferation both during development and cancer, but its role in response to ischemic injury is less well understood. The purpose of this study was to understand whether Notch-2 is induced after neonatal stroke and to investigate its functional relevance. METHODS-: P12 CD1 mice were subjected to permanent unilateral (right-sided) double ligation of the common carotid artery. RESULTS-: Neonatal ischemia induces a progressive brain injury with prolonged apoptosis and Notch-2 up-regulation. Notch-2 expression was induced shortly after injury in hippocampal areas with elevated c-fos activation and increased cell death. Long-term induction of Notch-2 also occurred in CA1 and CA3 in and around areas of cell death, and had a distinct pattern of expression as compared to Notch-1. In vitro oxygen glucose deprivation treatment showed a similar increase in Notch-2 in apoptotic cells. In vitro gain of function experiments, using an active form of Notch-2, show that Notch-2 induction is neurotoxic to a comparable extent as oxygen glucose deprivation treatment. CONCLUSIONS-: These results suggest that Notch-2 up-regulation after neonatal ischemia is detrimental to neuronal survival.

Original languageEnglish (US)
Pages (from-to)S64-S71
JournalStroke
Volume41
Issue number10 SUPPL. 1
DOIs
StatePublished - Oct 2010

Keywords

  • Notch-2
  • apoptosis
  • c-fos
  • hippocampus
  • neonatal stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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