Mayo Clinic Laboratory and Pathology Research Roundup: August 17
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The research roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.
Featured Abstract
TSPAN5 Influences Serotonin and Kynurenine: Pharmacogenomic Mechanisms Related to Alcohol Use Disorder and Acamprosate Treatment Response.
We previously reported that SNPs near TSPAN5 were associated with plasma serotonin (5-HT) concentrations which were themselves associated with selective serotonin reuptake inhibitor treatment outcomes in patients with major depressive disorder (MDD). TSPAN5 SNPs were also associated with alcohol consumption and alcohol use disorder (AUD) risk. The present study was designed to explore the biological function of TSPAN5 with a focus on 5-HT and kynurenine concentrations in the tryptophan pathway. Ethanol treatment resulted in decreased 5-HT concentrations in human induced pluripotent stem cell (iPSC)-derived neuron culture media, and the downregulation of gene expression of TSPAN5, DDC, MAOA, MAOB, TPH1, and TPH2 in those cells. Strikingly, similar observations were made when the cells were treated with acamprosate-an FDA approved drug for AUD therapy. These results were replicated in iPSC-derived astrocytes. Furthermore, TSPAN5 interacted physically with proteins related to clathrin and other vesicle-related proteins, raising the possibility that TSPAN5 might play a role in vesicular function in addition to regulating expression of genes associated with 5-HT biosynthesis and metabolism. Downregulation of TSPAN5 expression by ethanol or acamprosate treatment was also associated with decreased concentrations of kynurenine, a major metabolite of tryptophan that plays a role in neuroinflammation. Knockdown of TSPAN5 also influenced the expression of genes associated with interferon signaling pathways. Finally, we determined that TSPAN5 SNPs were associated with acamprosate treatment outcomes in AUD patients. In conclusion, TSPAN5 can modulate the concentrations of 5-HT and kynurenine. Our data also highlight a potentially novel pharmacogenomic mechanism related to response to acamprosate. Via Molecular Psychiatry.
Published to PubMed This Week
- Indoor Environment and Viral Infections.
Mayo Clinic Proceedings - Seasonality of Coronavirus 229E, HKU1, NL63, and OC43 From 2014 to 2020.
Mayo Clinic Proceedings - Guillain-Barré Syndrome in a Patient With Evidence of Recent SARS-CoV-2 Infection.
Mayo Clinic Proceedings - Hyalinizing Trabecular Tumor of the Thyroid.
Mayo Clinic Proceedings - The Long-Term Outcomes of Patients with Immunoglobulin G4-Related Sclerosing Cholangitis: The Mayo Clinic Experience.
Journal of Gastroenterology - Clinical Concept Extraction: A Methodology Review.
Journal of Biomedical Information - Duodenal Mucosal Secretory Disturbances in Functional Dyspepsia.
Neurogastroenterology and Motility - Clinical Predictors and Timing of Cessation of Viral RNA Shedding in Patients with COVID-19.
Journal of Clinical Virology - Evaluation of Automated Synovial Fluid Total Cell Count and Percent Polymorphonuclear Leukocytes on a Sysmex XN-1000 Analyzer for Identifying Patients at Risk of Septic Arthritis.
Clinical Chimica Acta - Obstructive Sleep Apnea Evaluation in Retinal Vein Occlusion Patients: An Opportunity for Multidisciplinary Care?
Cancer Journal of Ophthalmology
