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Dataset Details (GSE161848)

Superfund Research Program

Title: An epoxide hydrolase inhibitor reduces neuroinflammation in a mouse model of Alzheimer’s disease

Accession Number: GSE161848

Link to Dataset:

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Expression profiling by array

Organism(s): Mus musculus

Summary: Neuroinflammation has been increasingly recognized to play a critical role in Alzheimer’s disease (AD). The epoxy fatty acids (EpFAs) are derivatives of the arachidonic acid metabolism pathway and have anti-inflammatory activities. However, their efficacy is limited due to their rapid hydrolysis by the soluble epoxide hydrolase (sEH). We report that sEH is predominantly expressed in astrocytes and its concentrations are elevated in postmortem brain tissue from AD patients and in the 5xFAD -amyloid mouse model of AD. The amount of sEH expressed in AD mouse brains correlated with a reduction in brain EpFA concentrations. Using a specific small molecule sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), we report that TPPU treatment protected AD mice against LPS-induced inflammation in vivo. Long-term administration of TPPU to the 5xFAD mouse model via drinking water reversed microglia and astrocyte reactivity and immune pathway dysregulation. This was associated with reduced β-amyloid pathology and improved synaptic integrity and cognitive function on two behavioral tests. Importantly, TPPU treatment correlated with an increase in EpFA concentrations in the brains of 5xFAD mice, demonstrating brain penetration and target engagement. These findings support further investigation of TPPU as a potential therapeutic agent for the treatment of AD.

Publication(s) associated with this dataset:
  • Meragawi SE, Akbari A, Hernandez S, Sharifzadeh Mirshekarloo M, Bhattacharyya D, Tanksale A, Majumder M. 2020. Enhanced permselective separation of per-fluorooctanoic acid in graphene oxide membranes by a simple PEI modification. J Mater Chem 12:17. doi:10.1126/scitranslmed.abb1206 PMID:33298560
Project(s) associated with this dataset:
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