Date of Graduation

Summer 2016

Document Type

Honors Research Project

Degree Name

Bachelor of Science

Research Sponsor

Dr. Leah Shriver

First Reader

Dr. Jordan Renna

Second Reader

Dr. Rolando J.J. Ramirez

Abstract

Inflammation is a significant component of neurological diseases such as multiple sclerosis (MS). One potential anti-inflammatory agent, rolipram, was tested for efficacy in MS; however, despite showing promise in early trials, the drug has been largely sidelined due to side effects. However, it is still of interest to elucidate the anti-inflammatory mechanisms of rolipram in order to identify more targeted inhibitors of inflammatory signaling. In order to achieve this end, we have utilized liquid chromatography-mass spectrometry-based metabolomics to determine metabolic pathways that are altered by rolipram treatment in human THP-1 monocytic cells and primary mouse microglial cultures. Amino acids and related metabolites as well as steroid species were identified as being significantly dysregulated. Shotgun lipidomics showed upregulation of glycerophospholipids, including phosphatidylcholine and phosphatidylserine after rolipram treatment. Taken together, these results suggest that rolipram inhibition of cAMP breakdown leads to significant alterations on the metabolome of monocytic immune cells.

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Biology Commons

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