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Modulation of PKA, PKC, CAMKII, ERK 1/2 pathways is involved in the acute antidepressant-like effect of (octylseleno)-xylofuranoside (OSX) in mice

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Abstract

Rationale

(Octylseleno)-xylofuranoside (OSX) is an organoselenium compound from the class of alkylseleno carbohydrates possessing a C8 alkyl chain. Members of this class of organoselenium compounds have promising pharmacological activities, among them are antioxidant and acute antidepressant-like activities with the involvement of monoaminergic system, as previously presented by our research group.

Objective

The objective of the study was to investigate the possible involvement of cellular signalling pathways in the antidepressant-like effect caused by OSX (0.01 mg/kg, oral route (p.o.) by gavage) in the tail suspension test (TST) in mice.

Methods

Mice were treated by intracerebroventricular (i.c.v.) injection either with vehicle or with H-89 (1 μg/site i.c.v., an inhibitor of protein kinase A-PKA), KN-62 (1 μg/site i.c.v., an inhibitor of Ca2+/calmodulin-dependent protein kinase II-CAMKII), chelerythrine (1 μg/site i.c.v., an inhibitor of protein kinase C-PKC) or PD098059 (5 μg/site i.c.v., an inhibitor of extracellular-regulated protein kinase 1/2-ERK1/2). Fifteen minutes after, vehicle or OSX was injected, and 30 min later, the TST and open field tests (OFT) were carried out.

Results

The antidepressant-like effect of orally administered OSX was blocked by treatment of the mice with H-89, KN-62, chelerythrine and PD098059; all inhibitors of signalling proteins involved with neurotrophic signalling pathways. The number of crossings in the OFT was not altered by treatment with OSX and/or signalling antagonists.

Conclusions

The results demonstrated that OSX showed an antidepressant-like effect in the TST in mice through the activation of protein kinases PKA, PKC, CAMKII and ERK1/2 that are involved in intracellular signalling pathways.

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Acknowledgments

This study was supported by grants from the “Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)”, the “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)” and the “Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)”.

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Authors and Affiliations

  1. Programa de Pós Graduação em Biotecnologia, PPGBiotec, Grupo de Pesquisa em Neurobiotecnologia - GPN, CDTec, Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brazil

    Lucimar M. Pinto Brod, Mariana G. Fronza & Lucielli Savegnago

  2. Instituto de Química, Universidade Federal do Rio Grande do Sul, UFRGS, Av. Bento Gonçalves 9500, Porto Alegre, RS, 91501-970, Brazil

    Jaqueline Pinto Vargas & Diogo S. Lüdtke

  3. Núcleo de Síntese, Aplicação e Análise de Compostos Orgânicos e Inorgânicos, Universidade Federal da Fronteira Sul, Cerro Largo, RS, Brazil

    César Augusto Brüning

  4. Programa de Pós Graduação em Bioquímica e Bioprospecção, PPGBBio, Grupo de Pesquisa em Neurobiotecnologia - GPN, CCQFA, Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brazil

    Lucielli Savegnago

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  1. Lucimar M. Pinto Brod
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  2. Mariana G. Fronza
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  3. Jaqueline Pinto Vargas
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  4. Diogo S. Lüdtke
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  5. César Augusto Brüning
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  6. Lucielli Savegnago
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Corresponding author

Correspondence to Lucielli Savegnago.

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All procedures in this study were performed in accordance with the guidelines of the Committee on the Care and Use of Experimental Animal Resources at the Federal University of Pelotas, Brazil (8967–2013).

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The authors declare that they have no conflicts of interest.

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Pinto Brod, L.M., Fronza, M.G., Vargas, J.P. et al. Modulation of PKA, PKC, CAMKII, ERK 1/2 pathways is involved in the acute antidepressant-like effect of (octylseleno)-xylofuranoside (OSX) in mice. Psychopharmacology 234, 717–725 (2017). https://doi.org/10.1007/s00213-016-4505-5

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