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

Authors
  • Manosso, Luana M1
  • Moretti, Morgana2
  • Ribeiro, Camille M1
  • Gonçalves, Filipe M1
  • Leal, Rodrigo B1
  • Rodrigues, Ana Lúcia S3
  • 1 Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil. , (Brazil)
  • 2 Department of Natural Sciences, Universidade Regional de Blumenau, Blumenau 89012-900, SC, Brazil. , (Brazil)
  • 3 Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil. Electronic address: [email protected] , (Brazil)
Type
Published Article
Journal
Progress in neuro-psychopharmacology & biological psychiatry
Publication Date
Jun 03, 2015
Volume
59
Pages
59–67
Identifiers
DOI: 10.1016/j.pnpbp.2015.01.008
PMID: 25600102
Source
Medline
Keywords
License
Unknown

Abstract

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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