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


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 TNF?. 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.

SUBMITTER: Corbett BF 

PROVIDER: S-EPMC6637233 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Corbett Brian F BF   Luz Sandra S   Arner Jay J   Pearson-Leary Jiah J   Sengupta Abhishek A   Taylor Deanne D   Gehrman Philip P   Ross Richard R   Bhatnagar Seema S  

Nature communications 20190717 1


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 phenot  ...[more]

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