title: Immune malfunction in the GPR39 zinc receptor of knockout mice: Its relationship to depressive disorder.
abstract: Depression is a serious psychiatric disorder affecting not only the monaminergic, glutamatergic, and GABAergic neurosystems, but also the immune system. Patients suffering from depression show disturbance in the immune parameters as well as increased susceptibility to infections. Zinc is well known as an anti-inflammatory agent, and its link with depression has been proved, zinc deficiency causing depression- and anxiety-like behavior with immune malfunction. It has been discovered that trace-element zinc acts as a neurotransmitter in the central nervous system via zinc receptor GPR39. In this study we investigated whether GPR39 knockout would cause depressive-like behavior as measured by the forced swim test, and whether these changes would coexist with immune malfunction. In GPR39 knockout mice versus a wild-type control we found: i) depressive-like behavior; ii) significantly reduced thymus weight; (iii) reduced cell viability of splenocytes; iv) reduced proliferative response of splenocytes; and v) increased IL-6 production of splenocytes after ConA stimulation and decreased IL-1b and IL-6 release after LPS stimulation. The results indicate depressive-like behavior in GPR39 KO animals with an immune response similar to that observed in depressive disorder. Here for the first time we show immunological changes under GPR39-deficient conditions.
authors: Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland. Electronic address: katarzyna.mlyniec@uj.edu.pl.
authors: Katarzyna
authors: K
authors: Młyniec
authors: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PeL 31-343 Kraków, Poland.
authors: Ewa
authors: E
authors: Trojan
authors: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PeL 31-343 Kraków, Poland.
authors: Joanna
authors: J
authors: Ślusarczyk
authors: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PeL 31-343 Kraków, Poland.
authors: Katarzyna
authors: K
authors: Głombik
authors: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PeL 31-343 Kraków, Poland.
authors: Agnieszka
authors: A
authors: Basta-Kaim
authors: Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PeL 31-343 Kraków, Poland; Department of Biochemical Toxicology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
authors: Bogusława
authors: B
authors: Budziszewska
authors: 1st Department of Psychiatry, Medical University of Warsaw, Nowowiejski Hospital, Nowowiejska 27, PL 02-156 Warszawa, Poland.
authors: Jakub
authors: J
authors: Skrzeszewski
authors: Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
authors: Agata
authors: A
authors: Siwek
authors: Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
authors: Birgitte
authors: B
authors: Holst
authors: Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland; Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PeL 31-343 Kraków, Poland.
authors: Gabriel
authors: G
authors: Nowak
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000235:genetics; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D003866:Depressive Disorder / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009929:Organ Size / Q000235:genetics; D010078:Oxazines / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013550:Swimming / Q000523:psychology; D060168:Thymocytes / Q000187:drug effects / Q000473:pathology; D014966:Xanthenes / Q000378:metabolism
chemical_list: D016207:Cytokines; C512928:GPR39 protein, mouse; D008070:Lipopolysaccharides; D008934:Mitogens; D010078:Oxazines; D043562:Receptors, G-Protein-Coupled; D014966:Xanthenes; D003208:Concanavalin A; C005843:resazurin
keywords: Depression; GPR39; Immune system; Proliferation; Zinc