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A role for GPR83, a newly deorphanized G protein‐coupled receptor, in stress‐induced neuroimmune modulation
Author(s) -
Lueptow Lindsay Mariah,
Gomes Ivone,
Fakira Amanda,
Devi Lakshmi A
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.988.1
Subject(s) - hypothalamus , corticosterone , biology , dorsal raphe nucleus , amygdala , medicine , neuroscience , endocrinology , nucleus accumbens , periaqueductal gray , microbiology and biotechnology , receptor , central nervous system , serotonin , hormone , midbrain , serotonergic
GPR83 is a recently deorphanized G‐protein coupled receptor (GPCR) found to be widely expressed throughout the brain and immune system of mice. Analysis of expression reveals high levels in discrete brain regions, such as nucleus accumbens, hypothalamus, amygdala and hippocampus, regions known to be involved in stress modulation, anxiety, depression, and memory. Previous studies have reported that GPR83 is regulated by the stress hormone corticosterone and that GPR83 knockout mice are resistant to stress‐induced anxiety, despite having similar increases in plasma corticosterone as wild type mice. Because stress is known to have a profound effect on immune function, we have recently begun to explore a role for GPR83 in neuroimmune interactions during stress. Using flow cytometry, we have identified the immune cell types that express GPR83. We find GPR83 expression on CD4+ and CD8+ T‐cell populations, as well as a small portion of B cells and natural killer cells. To explore the neuronal pathway that activates GPR83 in these cells, we sought to map the projections from the brain to the spleen and thymus. For this, we injected attenuated pseudorabies virus tagged with GFP into the spleen and thymus and examined viral expression following 72 hrs of retrograde transport. Expression was observed in portions of the reticular formation (notably gigantocellular reticular nucleus), nucleus raphe magnus, dorsal raphe nucleus, and periaqueductal grey. There was strong expression in the paraventricular hypothalamus and in the gray matter cells of the subthalamus, known as the zona incerta. Most interestingly, projections to the central amygdala and anterior insular cortex were also observed. Since many of these brain regions are involved in somatic regulation, fear learning and response to stress, as well as pain modulation, these results are consistent with a role for the GPR83‐PEN receptor system as a mediator of neuroimmune interactions. Support or Funding Information Funding: NS026880 and DA019521 to L.A.D and T32 grant DA007135 to L.M.L.