Lucimar M Pinto Brod1, Mariana G Fronza1, Jaqueline Pinto Vargas2, Diogo S Lüdtke2, César Augusto Brüning3, Lucielli Savegnago4,5. 1. Programa de Pós Graduação em Biotecnologia, PPGBiotec, Grupo de Pesquisa em Neurobiotecnologia - GPN, CDTec, Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brazil. 2. Instituto de Química, Universidade Federal do Rio Grande do Sul, UFRGS, Av. Bento Gonçalves 9500, Porto Alegre, RS, 91501-970, Brazil. 3. Núcleo de Síntese, Aplicação e Análise de Compostos Orgânicos e Inorgânicos, Universidade Federal da Fronteira Sul, Cerro Largo, RS, Brazil. 4. Programa de Pós Graduação em Biotecnologia, PPGBiotec, Grupo de Pesquisa em Neurobiotecnologia - GPN, CDTec, Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brazil. luciellisavegnago@yahoo.com.br. 5. Programa de Pós Graduação em Bioquímica e Bioprospecção, PPGBBio, Grupo de Pesquisa em Neurobiotecnologia - GPN, CCQFA, Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brazil. luciellisavegnago@yahoo.com.br.
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.
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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