Keap1/Nrf2/HO-1 signaling pathway contributes to p-chlorodiphenyl diselenide antidepressant-like action in diabetic mice.

Rationale: The association between depression and diabetes has been recognized for many years, but the nature of this relationship remains uncertain. Objectives: This study investigated the antidepressant-like effect of (p-ClPhSe)2 on mice made diabetic by streptozotocin (STZ) and the contribution o...

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Publicado en:Psychopharmacology Vol. 237; no. 2; pp. 363 - 375
Autores principales: Zborowski, Vanessa A., Heck, Suélen O., Vencato, Marina, Pinton, Simone, Marques, Luiza S., Nogueira, Cristina W.
Formato: Journal Article
Publicado: Springer Nature Feb2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Feb2020
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      pub: Springer Nature
      place: New York, New York
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        141727129
        10.1007/s00213-019-05372-3
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        atl: Keap1/Nrf2/HO-1 signaling pathway contributes to p-chlorodiphenyl diselenide antidepressant-like action in diabetic mice.
      aug:
        au:
          Zborowski, Vanessa A.
          Heck, Suélen O.
          Vencato, Marina
          Pinton, Simone
          Marques, Luiza S.
          Nogueira, Cristina W.
        affil: 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, 97105-900, Santa Maria, RS, Brazil
      sug:
      ab: Rationale: The association between depression and diabetes has been recognized for many years, but the nature of this relationship remains uncertain. Objectives: This study investigated the antidepressant-like effect of (p-ClPhSe)2 on mice made diabetic by streptozotocin (STZ) and the contribution of cerebral cortical Keap1/Nrf2/HO-1 signaling pathway for this effect. Methods: Male adult Swiss mice received streptozotocin (STZ, 200 mg/kg, i.p.) to induce diabetes (glycemia ≥ 200 mg/dl) or citrate buffer (5 ml/kg, control group). The mice were treated with (p-ClPhSe)2 at the dose of 5 mg/kg, i.g., for 7 days. Mice performed behavior tests, tail suspension (TST), and forced swimming tests (FST), to evaluate depressive-like phenotype. Results: Diabetic mice showed an increase in immobility time in the TST and FST when compared to the control group. The protein contents of Keap1/Nrf2/HO-1 pathway were decreased in the cerebral cortex of diabetic mice. Diabetic mice had an increase in the relative adrenal weight and a decrease in the protein content of glucocorticoid receptor. The levels of TBARS and RS and SOD activity were found altered in the cerebral cortex of diabetic mice. The number of FJC-positive cells was increased in the cerebral cortex of diabetic mice. Treatment with (p-ClPhSe)2 was effective against depressive-like phenotype, oxidative stress, and FJC-positive cells of diabetic mice. (p-ClPhSe)2 did not reverse the parameters of HPA axis evaluated in this study. (p-ClPhSe)2 modulated the cerebral cortical Keap1/Nrf2/HO-1 pathway in diabetic mice. Conclusions: This study demonstrates the contribution of cerebral cortical Keap1/Nrf2/HO-1 pathway in the (p-ClPhSe)2 antidepressant-like action in diabetic mice.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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