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 language | English (US) |
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Pages (from-to) | 2215-2219 |
Number of pages | 5 |
Journal | Neurobiology of aging |
Volume | 33 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2012 |
Externally published | Yes |
Keywords
- Beta-amyloid
- Cyclooxygenase
- Neuroinflammation
- Prostaglandin E
- Stroke
ASJC Scopus subject areas
- Clinical Neurology
- Geriatrics and Gerontology
- Aging
- General Neuroscience
- Developmental Biology