PGE 2 EP1 receptor exacerbated neurotoxicity in a mouse model of cerebral ischemia and Alzheimer's disease

Gehua Zhen, Yun Tai Kim, Rung chi Li, Jennifer Yocum, Nidhi Kapoor, John Langer, Peter Dobrowolski, Takayuki Maruyama, Shuh Narumiya, Sylvain Doré

Research output: Contribution to journalArticlepeer-review

Abstract

Stroke and Alzheimer's disease (AD) are major age-related neurodegenerative diseases that may worsen the prognosis of each other. Our study was designed to delineate the prostaglandin E 2 EP1 receptor role in AD and in the setting of cerebral ischemia. Genetic deletion of the prostaglandin EP1 receptor significantly attenuated the more severe neuronal damage (38.5 ± 10.6%) and memory loss induced by ischemic insult observed in AD transgenic mice (percentage of viable hippocampal CA1 neurons: 11.2 ± 2.9%) when compared with wild type mice (45.1 ± 9.1%). In addition, we found that the amyloid plaques were reduced in EP1 deleted AD mice. β-amyloid-induced toxicity (18.0 ± 7.1%) and Ca 2+ response (91.8 ± 12.9%) were also reduced in EP1 -/- neurons compared with control neurons in in vitro. Hence, EP1 might mediate most of the toxicity associated with cyclooxygenase-2 and contribute substantially to the cell death pathways in AD and stroke. Exploring potential therapeutic agent targeting EP1 receptor could potentially benefit treatments for stroke and AD patients.

Original languageEnglish (US)
Pages (from-to)2215-2219
Number of pages5
JournalNeurobiology of aging
Volume33
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Beta-amyloid
  • Cyclooxygenase
  • Neuroinflammation
  • Prostaglandin E
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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