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(p-ClPhSe)2 modulates hippocampal BDNF/TrkB signaling and reverses memory impairment induced by diabetes in mice.
Zborowski, Vanessa A; Heck, Suélen O; Sari, Marcel H M; Bastos, Nícolas K; Neto, José S S; Nogueira, Cristina W.
Afiliação
  • Zborowski VA; Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria - RS 97105-900, Brazil.
  • Heck SO; Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria - RS 97105-900, Brazil.
  • Sari MHM; Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria - RS 97105-900, Brazil.
  • Bastos NK; Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria - RS 97105-900, Brazil.
  • Neto JSS; Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria - RS 97105-900, Brazil.
  • Nogueira CW; Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria - RS 97105-900, Brazil. Electronic address: criswn@uf
Article em En | MEDLINE | ID: mdl-31152861
Diabetes is a metabolic disease characterized by hyperglycemia because of insulin resistance and/or insufficient insulin release. The most common diabetic brain complications include cognitive decline and depression. The present study investigated whether the 4-4'-dichlorodiphenyl diselenide (p-ClPhSe)2 is effective against memory impairment induced by diabetes in mice and the role of hippocampal BDNF/TrkB signaling in this effect. Male adult Swiss mice received an injection of streptozotocin (STZ) (200 mg/kg, i.p.) to induce diabetes. The results revealed that STZ injection in mice resulted in resilience (glycemia <200 mg/dl) or diabetes (glycemia ≥200 mg/dl). The vehicle-control group received citrate buffer (5 ml/kg). The animals were subchronically treated with (p-ClPhSe)2 (1 or 5 mg/kg, i.g.) for 7 days. Mice performed a battery of well-validated behavior tests designated to evaluate memory, object recognition (ORT), object location (OLT), and Morris water maze (MWM). The hippocampal protein contents of the BDNF/TrkB pathway were determined in the samples of experimental groups. Fluoro Jade C (FJC) was used for staining degenerating neurons. The STZ administration resulted in memory impairment that was demonstrated in the mouse ORT, OLT, and MWM tests. The molecular findings indicate an increase in hippocampal protein levels of proBDNF and TrKB but a decrease in those of mBDNF and pCREB in diabetic mice. The number of FJC-positive cells was increased in the hippocampus of diabetic mice. (p-ClPhSe)2 at the dose of 5 mg/kg modulated the hippocampal BDNF/TrkB pathway, reduced FJC-positive cells and reversed memory impairment induced by STZ in mice. These findings demonstrate the effectiveness of (p-ClPhSe)2 against memory impairment caused by diabetes in mice. (p-ClPhSe)2 modulated the hippocampal BDNF/TrkB signaling pathway in diabetic mice.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Compostos Organosselênicos / Fator Neurotrófico Derivado do Encéfalo / Receptor trkB / Diabetes Mellitus Experimental / Hipocampo / Transtornos da Memória Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Compostos Organosselênicos / Fator Neurotrófico Derivado do Encéfalo / Receptor trkB / Diabetes Mellitus Experimental / Hipocampo / Transtornos da Memória Idioma: En Ano de publicação: 2019 Tipo de documento: Article