Sphingosine-1-phosphate receptor 3 in the medial prefrontal cortex promotes stress resilience by reducing inflammatory processes

Brian F. Corbett, Sandra Luz, Jay Arner, Jiah Pearson-Leary, Abhishek Sengupta, Deanne Taylor, Philip Gehrman, Richard Ross and Seema Bhatnagar ()
Additional contact information
Brian F. Corbett: Abramson Research Center
Sandra Luz: Abramson Research Center
Jay Arner: Abramson Research Center
Jiah Pearson-Leary: Abramson Research Center
Abhishek Sengupta: Abramson Research Center
Deanne Taylor: Abramson Research Center
Philip Gehrman: University of Pennsylvania
Richard Ross: University of Pennsylvania
Seema Bhatnagar: Abramson Research Center

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Stress can promote the development of psychiatric disorders, though some individuals are more vulnerable to stress compared to others who are more resilient. Here we show that the sphingosine-1-phosphate receptor 3 (S1PR3) in the medial prefrontal cortex (mPFC) of rats regulates resilience to chronic social defeat stress. S1PR3 expression is elevated in the mPFC of resilient compared to vulnerable and control rats. Virally-mediated over-expression of S1PR3 in the mPFC produces a resilient phenotype whereas its knock-down produces a vulnerable phenotype, characterized by increased anxiety- and depressive-like behaviors, and these effects are mediated by TNFα. Furthermore, we show that S1PR3 mRNA in blood is reduced in veterans with PTSD compared to combat-exposed control subjects and its expression negatively correlates with symptom severity. Together, these data identify S1PR3 as a regulator of stress resilience and reveal sphingolipid receptors as important substrates of relevance to stress-related psychiatric disorders.

Date: 2019
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DOI: 10.1038/s41467-019-10904-8

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