Behavior in the forced swim test and neurochemical changes in the hippocampus in young rats after 2-week zinc deprivation

Tamano, Haruna; Kan, Fumika; Kawamura, Mika; Oku, Naoto; Takeda, Atsüshi

doi:10.1016/j.neuint.2009.05.011

Cited by 62 publications

(46 citation statements)

References 52 publications

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“…Recently, zinc monotherapy was reported to improve mood in overweight or obese subjects most likely by increasing BDNF levels (Solati et al, 2014). Consistent with these data, it is well established that zinc supplementation provides an antidepressant-like effect in predictive tests for antidepressant activity (Brocardo et al, 2007;Cunha et al, 2008;Franco et al, 2008;Kroczka et al, 2001;Lobato et al, 2008;Nowak et al, 2003;Rosa et al, 2003;Sowa-Kucma et al, 2008;Szewczyk et al, 2009) and zinc-deficient diet leads to a depressive-like effect Mlyniec and Nowak, 2012;Tamano et al, 2009;Tassabehji et al, 2008;Whittle et al, 2009).…”

Section: Introductionmentioning

confidence: 74%

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Manosso

Moretti

Ribeiro

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Considering that intracellular signaling pathways that modulate brain BDNF are implicated in antidepressant responses, this study investigated whether signaling pathway inhibitors upstream to BDNF might influence the antidepressant-like effect of zinc, a metal that has been shown to display antidepressant properties. To this end, the influence of i.c.v. administration of H-89 (1μg/site, PKA inhibitor), KN-62 (1μg/site, CAMKII inhibitor), chelerythrine (1μg/site, PKC inhibitor), PD98059 (5μg/site, MEK1/2 inhibitor), U0126 (5μg/site, MEK1/2 inhibitor), LY294002 (10nmol/site, PI3K inhibitor) on the reduction of immobility time in the tail suspension test (TST) elicited by ZnCl2 (10mg/kg, p.o.) was investigated. Moreover, the effect of the combination of sub-effective doses of ZnCl2 (1mg/kg, p.o.) and AR-A014418 (0.001μg/site, GSK-3β inhibitor) was evaluated. The occurrence of changes in CREB phosphorylation and BDNF immunocontent in the hippocampus and prefrontal cortex of mice following ZnCl2 treatment was also investigated. The anti-immobility effect of ZnCl2 in the TST was prevented by treatment with PKA, PKC, CAMKII, MEK1/2 or PI3K inhibitors. Furthermore, ZnCl2 in combination with AR-A014418 caused a synergistic anti-immobility effect in the TST. None of the treatments altered locomotor activity of mice. ZnCl2 treatment caused no alteration in CREB phosphorylation and BDNF immunocontent. The results extend literature data regarding the mechanisms underlying the antidepressant-like action of zinc by indicating that its antidepressant-like effect may be dependent on the activation of PKA, CAMKII, PKC, ERK, and PI3K/GSK-3β pathways. However, zinc is not able to acutely increase BDNF in the hippocampus and prefrontal cortex.

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Section: Introductionmentioning

confidence: 74%

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Manosso

Moretti

Ribeiro

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Dysfunction of the HPA system plays an important role in mood disorders such as depression; downregulation of the HPA system increases the synthesis of corticosteroid hormones, such as the catecholamines and cortisol [10]. Thus, it seems likely that zinc deficiency in patients with depression may alter hippocampal function, resulting in abnormalities in the secretion of corticosteroids [27]. Induced hyperactivity of the HPA system in depressed patients, caused by increased zinc or other factors, could result in changes in the blood-brain barrier through deregulation of the multidrug resistance protein pglycoprotein (MDR PGP) [10,28].…”

Section: Discussionmentioning

confidence: 99%

Dietary Intake of Zinc was Inversely Associated with Depression

Yary

Aazami

2011

Biol Trace Elem Res

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Depression is an important cause of morbidity, and World Health Organization has predicted that it will be the second leading contributor to the global burden of disease by 2020. Postgraduate students are at high risk for depression caused by the stress of examinations, the academic environment, and relationship problems with peers, lecturers, and family members. Physical inactivity, advancing age, unmarried status, and many other factors contribute to the development of depression in humans. Associations between symptoms of depression and the intake of nutrients such as magnesium have been investigated; however, the relationship between zinc intake and depression has not received as much attention. The purpose of the present study was to examine the relationship between dietary intake of zinc and depression in postgraduate students. This study was conducted on 402 participants with a mean age of 32.54 ± 6.22 years, including 173 (43%) women and 229 (57%) men. In this study, we found an inverse relationship between dietary intake of zinc and depression. The results persisted even after we controlled for several potential confounding variables related to depression symptoms, including age, sex, years of education, smoking status (current and past), and physical activity. The results of this study show that long-term intake of zinc may modulate symptoms of depression.

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“…3). The increase in depression-like behavior is reported in zinc-deficient mice [111] and rats [112], and is observed in no appreciable decrease in zinc concentration in the brain [113]. Neuropsychological symptoms are caused prior to the decreases in histochemically reactive zinc and/or extracellular zinc in the brain, which are responsive to zinc deficiency [109,110,114,115].…”

Section: Zinc Deficiency and Depressionmentioning

confidence: 98%

“…Both zinc deficiency and aging, in addition to stress, seem to be risk factors for depression glucocorticoid level, which is linked to the increased HPA axis activity, might be linked to more susceptibility to stress-related disorders such as depression in aged humans [38]. The increase in the basal Ca 2+ level and modification of Ca 2+ signaling in the hippocampal cells are observed in both aged [123,124] and zinc-deficient [109,113,125,126] animals. Glucocorticoids are associated with these changes in the hippocampus.…”

Section: Zinc Homeostasis the Hpa System And Stress Susceptibility Imentioning

confidence: 99%

Zinc Signaling in the Hippocampus and Its Relation to Pathogenesis of Depression

Takeda

2010

Mol Neurobiol

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Zinc is released from glutamatergic (zincergic) neuron terminals in the brain, followed by the increase in Zn²⁺ concentration in the intracellular (cytosol) compartment as well as that in the extracellular compartment. Intracellular Zn²⁺ concentration mainly increases through calcium-permeable channels and serves as Zn²⁺ signal as well as extracellular Zn²⁺ concentration. Hippocampal Zn²⁺ signaling may participate in synaptic plasticity such as long-term potentiation and cognitive function. On the other hand, subclinical zinc deficiency is common in the old who might be more susceptible to depression. Zinc deficiency causes abnormal glucocorticoid secretion and increases depression-like behavior in animals. Neuropsychological symptoms are observed prior to the decrease in Zn²⁺ signal in the hippocampus under zinc deficiency. This paper summarizes that hippocampal Zn²⁺ signaling serves to maintain healthy brain and that glucocorticoid signaling, which is responsive to zinc homeostasis in the living body, is linked to the pathophysiology of depression.

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Behavior in the forced swim test and neurochemical changes in the hippocampus in young rats after 2-week zinc deprivation

Cited by 62 publications

References 52 publications

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Dietary Intake of Zinc was Inversely Associated with Depression

Zinc Signaling in the Hippocampus and Its Relation to Pathogenesis of Depression

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