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Involvement of glutamatergic neurotransmission in the antidepressant-like effect of zinc in the chronic unpredictable stress model of depression

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

Stress and excessive glutamatergic neurotransmission have been implicated in the pathophysiology of depression. Therefore, this study was aimed at investigating the influence of zinc on depressive-like behavior induced by chronic unpredictable stress (CUS), on alterations in glutamate-induced toxicity and immunocontent of proteins involved in the control of glutamatergic neurotransmission in the hippocampus of mice. Mice were subjected to CUS procedure for 14 days. From the 8th to the 14th day, mice received zinc chloride (ZnCl2) (10 mg/kg) or fluoxetine (10 mg/kg, positive control) once a day by oral route. CUS caused a depressive-like behavior evidenced by the increased immobility time in the tail suspension test (TST), which was prevented by treatment with ZnCl2 or fluoxetine. Ex vivo exposure of hippocampal slices to glutamate (10 mM) resulted in a significant decrease on cell viability; however, neither CUS procedure nor drug treatments altered this reduction. No alterations in the immunocontents of GLT-1 and GFAP or p-Akt were observed in any experimental group. The ratio of p-Akt/AKT was also not altered in any group. However, Akt immunocontent was increased in stressed mice and in animals treated with ZnCl2 (stressed or non-stressed mice) and EAAC1 immunocontent was increased in stressed mice treated with ZnCl2, fluoxetine or vehicle and in non-stressed mice treated with ZnCl2 and fluoxetine. These findings indicate a robust effect of zinc in reversing behavioral alteration induced by CUS in mice, through a possible modulation of the glutamatergic neurotransmission, extending literature data regarding the mechanisms underlying its antidepressant-like action.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

CUS:

Chronic unpredictable stress

EAATs:

Excitatory amino acid transporters

GFAP:

Glial fibrillary acidic protein

MTT:

3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide

NMDA:

N-methyl-d-aspartate

OD:

Optical density

p.o.:

Per os

SEM:

Standard error of the mean

TST:

Tail suspension test

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Acknowledgments

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) # 308723/2013-9 and # 449436/2014-4, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), NENASC Project (PRONEX-FAPESC/CNPq) # 1262/2012-9 and CAPES/PVE 052/2012.

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  1. Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Luana M. Manosso, Morgana Moretti, André R. Colla, Camille M. Ribeiro, Tharine Dal-Cim, Carla I. Tasca & Ana Lúcia S. Rodrigues

  2. Post-Graduate Nutrition Program, Center of Health Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Morgana Moretti

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  1. Luana M. Manosso
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  2. Morgana Moretti
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Correspondence to Ana Lúcia S. Rodrigues.

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Manosso, L.M., Moretti, M., Colla, A.R. et al. Involvement of glutamatergic neurotransmission in the antidepressant-like effect of zinc in the chronic unpredictable stress model of depression. J Neural Transm 123, 339–352 (2016). https://doi.org/10.1007/s00702-015-1504-3

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