Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies
  1. Home
  3. Research Domains

NSAIDs prevent, but do not reverse, neuronal cell cycle reentry in a mouse model of Alzheimer disease.

Nicholas H Varvel1, Kiran Bhaskar, Maria Z Kounnas

  • 1Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.

The Journal of Clinical Investigation
|November 13, 2009

Related Experiment Videos

View abstract on PubMed

Summary

Related Concept Videos

  • Biomedical And Clinical Sciences
  • Oncology And Carcinogenesis
  • Predictive And Prognostic Markers
  • Nsaids Prevent, But Do Not Reverse, Neuronal Cell Cycle Reentry In A Mouse Model Of Alzheimer Disease.
    • This summary is machine-generated.

    Ectopic cell cycle events (CCEs) in Alzheimer disease (AD) are linked to microglial changes. Early nonsteroidal anti-inflammatory drug (NSAID) treatment in mice prevents CCEs, suggesting timely intervention is key for AD.

    Area of Science:

    • Neuroscience
    • Pathology
    • Pharmacology

    Background:

    • Ectopic cell cycle events (CCEs) are early indicators of neuronal vulnerability in Alzheimer disease (AD).
    • In AD mouse models, CCEs precede beta-amyloid peptide (Abeta) plaque formation.
    • Microglial alterations coincide with CCEs in the R1.40 AD mouse model.

    Purpose of the Study:

    • To investigate the relationship between inflammation, CCEs, and microglial changes in AD.
    • To evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing or reversing CCEs and associated pathology.
    • To explore the potential of CCEs as an early biomarker for therapeutic intervention in AD.

    Main Methods:

    • Utilized the R1.40 transgenic mouse model of AD.
    • Induced inflammation using lipopolysaccharide (LPS) in young R1.40 mice.
    • Administered NSAIDs to young and old R1.40 mice.
    • Assessed neuronal CCEs, microglial alterations, amyloid precursor protein (APP) processing, and Abeta levels.

    Main Results:

    • Inflammation induced by LPS accelerated the onset of neuronal CCEs in young R1.40 mice.
    • NSAID treatment in young R1.40 mice prevented neuronal CCEs and microglial changes without affecting APP processing or Abeta levels.
    • NSAID treatment in older R1.40 mice inhibited new CCEs but did not reverse existing ones.
    • NSAIDs did not alter steady-state Abeta levels or APP processing.

    Conclusions:

    • Early intervention with NSAIDs can prevent the emergence of neuronal CCEs and associated microglial alterations in an AD mouse model.
    • The timing of NSAID administration is critical, as it prevents new CCEs but does not reverse established ones.
    • CCEs serve as a sensitive outcome measure, potentially explaining discrepancies between retrospective and prospective NSAID studies in human AD.
    • Initiating NSAID therapy early in AD progression may be crucial for therapeutic benefit.

    Related Experiment Videos