TY - JOUR

T1 - Immune malfunction in the GPR39 zinc receptor of knockout mice

T2 - Its relationship to depressive disorder

AU - Młyniec, Katarzyna

AU - Trojan, Ewa

AU - Ślusarczyk, Joanna

AU - Głombik, Katarzyna

AU - Basta-Kaim, Agnieszka

AU - Budziszewska, Bogusława

AU - Skrzeszewski, Jakub

AU - Siwek, Agata

AU - Holst, Birgitte

AU - Nowak, Gabriel

N1 - Copyright © 2015 Elsevier B.V. All rights reserved.

PY - 2016/2/15

Y1 - 2016/2/15

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Proliferation

KW - Cell Survival

KW - Concanavalin A

KW - Cytokines

KW - Depressive Disorder

KW - Disease Models, Animal

KW - Female

KW - Gene Expression Regulation

KW - Lipopolysaccharides

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mitogens

KW - Motor Activity

KW - Organ Size

KW - Oxazines

KW - Receptors, G-Protein-Coupled

KW - Spleen

KW - Swimming

KW - Thymocytes

KW - Xanthenes

U2 - 10.1016/j.jneuroim.2015.12.001

DO - 10.1016/j.jneuroim.2015.12.001

M3 - Journal article

C2 - 26857489

VL - 291

SP - 11

EP - 17

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

ER -