Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid-β (Aβ) disease pathologies. Mice overexpressing both Aβ and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of Aβ accumulation in the brain and selectively increased the production of soluble Aβ42. PGI2 damaged the microvasculature through alterations in vascular length and branching; Aβ expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.
Document Type
Article
Publication Date
2-7-2022
Digital Object Identifier (DOI)
https://doi.org/10.3389/fncel.2022.769347
Funding Information
Research reported in this publication was supported by intramural funding from the University of Houston (JE), the NIA of the National Institutes of Health under award number 1R15AG039008 (JE), and the NHLBI R01HL146745 (DM).
Related Content
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Repository Citation
Womack, Tasha R.; Vollert, Craig T.; Ohia-Nwoko, Odochi; Schmitt, Monika; Montazari, Saghi; Beckett, Tina L.; Mayerich, David; Murphy, M. Paul; and Eriksen, Jason L., "Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s Disease" (2022). Molecular and Cellular Biochemistry Faculty Publications. 197.
https://uknowledge.uky.edu/biochem_facpub/197
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Electrical and Computer Engineering Commons, Pharmacy and Pharmaceutical Sciences Commons
Notes/Citation Information
Published in Frontiers in Cellular Neuroscience, v. 16, article 769347.
© 2022 Womack, Vollert, Ohia-Nwoko, Schmitt, Montazari, Beckett, Mayerich, Murphy and Eriksen
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