The role of the GPR39 receptor in zinc deficient-animal model of depression

Abstract

During the last decade it has been shown that zinc may activate neural transmissions via the GPR39 Zn(2+)-sensing receptor, which can be involved in the regulation of neuronal plasticity. According to the neurotrophic hypothesis of depression, decreased brain derived neurotrophic factor (BDNF) levels in depressed patients play a key role in the pathogenesis of this disorder. BDNF, similarly as zinc, is known to be involved in the process of neuron survival and the regulation of neuronal plasticity. The aim of the present study was to determine whether the administration of a 6-week diet deficient in zinc would cause depressive-like behaviour and if such behavioural alterations would correlate with changes in the expression of the BDNF protein and GPR39 receptor. In the first part of the present study the animal behaviour after a 6-week zinc-deficient diet, in the forced swim test (FST) was investigated. In the second part expression of the GPR39 and BDNF protein level in the frontal cortex was measured using the Western Blot method. Administration of a zinc-deficient diet for 6 weeks increased immobility time in the FST by 24%, so exerted depression-like behaviour. A biochemical study showed a significant reduction in GPR39 (by 53%) and BDNF (by 49%) protein expression in the frontal cortex in mice receiving the zinc deficient diet for 6 weeks. Our study provides evidence that the GPR39 Zn(2+)-sensing receptor may be responsible for lowering the BDNF protein level and in consequence may be involved in the pathogenesis of depression.