Intracerebral Administration of BDNF Protects Rat Brain Against Oxidative Stress Induced by Ouabain in an Animal Model of Mania

Valvassori, Samira S.; Arent, Camila O.; Steckert, Amanda V.; Varela, Roger B.; Jornada, Luciano K.; Tonin, Paula T.; Budni, Josiane; Mariot, Edemilson; Kapczinski, Flávio; Quevedo, Joao L De

doi:10.1007/s12035-014-8873-8

Cited by 36 publications

(28 citation statements)

References 71 publications

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“…Ouabain-induced decreases in frontal cortex BDNF mRNA and protein levels observed in the present study is consistent with past studies showing ouabain reduced BDNF expression in the frontal cortex (Valvassori et al, 2015a; Varela et al, 2015). Previous experiments have also demonstrated that treatment with mood stabilizers, i.e.…”

Section: Discussionsupporting

confidence: 93%

“…As observed in other studies investigating brain BDNF following central ouabain administration using an ELISA method (Varela et al, 2015; Valvassori et al, 2015a), the present experiment found a reduction in frontal cortex BDNF. We measured BDNF by Western blot and qPCR.…”

Section: Discussionsupporting

confidence: 90%

“…The ouabain model of mania is increasingly employed to further understand the neuropathophysiology of bipolar disorder (Decker et al, 2000; Herman et al, 2007; Kim et al, 2008,2013; Souza et al, 2014; Sui et al, 2013; Tonin et al, 2014;Valvassori et al, 2015a; Yu et al, 2010, 2011) and examine treatments that may alleviate defining symptoms in the disorder (Brocardo et al, 2011; Bruning et al, 2012; Gao et al, 2011; Jornada et al, 2011; Souza et al, 2014; Wang et al, 2013; Valvassori et al, 2015b). Ouabain principally acts as a Na+/K+ ATPase inhibitor and is meant to model reduced Na+/K+ ATPase activity observed in bipolar disorder individuals (Banerjee et al, 2012; Goldstein et al, 2009; Huff et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

et al. 2017

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Central infusion of the Na+/K+-ATPase inhibitor, ouabain in rats serves as an animal model of mania because it leads to hyperactivity, as well as reproduces ion dysregulation and reduced BDNF levels similar to that observed in bipolar disorder. Bipolar disorder is also associated with cognitive inflexibility and working memory deficits. It is unknown whether ouabain treatment in rats leads to similar cognitive flexibility and working memory deficits. The present study examined the effects of an intracerebral ventricular infusion of ouabain in rats on spontaneous alternation, probabilistic reversal learning and BDNF expression levels in the frontal cortex. Ouabain treatment significantly increased locomotor activity, but did not affect alternation performance in a Y-maze. Ouabain treatment selectively impaired reversal learning in a spatial discrimination task using an 80/20 probabilistic reinforcement procedure. The reversal learning deficit in ouabain-treated rats resulted from an impaired ability to maintain a new choice pattern (increased regressive errors). Ouabain treatment also decreased sensitivity to negative feedback during the initial phase of reversal learning. Expression of BDNF mRNA and protein levels was downregulated in the frontal cortex which also negatively correlated with regressive errors. These findings suggest that the ouabain model of mania may be useful in understanding the neuropathophysiology that contributes to cognitive flexibility deficits and test potential treatments to alleviate cognitive deficits in bipolar disorder.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

et al. 2017

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“…Reduced glutathione (GSH) is a tripeptide composed of cysteine, glycine, and glutamate, and it is used as an electron donor for GPx action, leading to the production of oxidized glutathione (GSSG). Another important enzyme of this system is glutathione reductase (GR), which is required to catalyze the reduction of GSSG to GSH [9, 10]. …”

Section: Introductionmentioning

confidence: 99%

HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway

Ding

Zou

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Human adipose-derived stem cells (hADSCs) are a potential therapeutic option for clinical applications because of their ability to produce cytokines and their capacity for trilineage differentiation. To date, few researchers have investigated the effects of hADSCs on natural ovarian aging (NOA). Methods: An NOA mouse model and human ovarian granule cells (hGCs) collected from individuals with NOA were prepared to assess the therapeutic effects and illuminate the mechanism of hADSCs in curing NOA. Enzyme-linked immunosorbent assay was used to detect the serum levels of sex hormones and antioxidative enzymes. The proliferation rate and marker expression level of hGCs were measured by flow cytometry (FACS). Cytokines were measured by a protein antibody array methodology. Western blot assays were used to determine the protein expression levels of SIRT1 and FOXO1. Results: Our results showed that hADSCs displayed therapeutic activity against ovarian function in an NOA mouse model, increasing the proliferation rate and marker expression level of hGCs. Furthermore, the yields of hADSC-secreted HGF and bFGF were higher than those of other growth factors. FACS showed that combination treatment with the growth factors HGF and bFGF more strongly promoted proliferation and inhibited apoptosis in hGCs than HGF or bFGF treatment alone. FACS and ELISA revealed that the combination treatment with both growth factors inhibited oxidative stress more forcefully than treatments with only one of these growth factors. In addition, protein assays demonstrated that combination treatment with both growth factors suppressed oxidative stress by up-regulating the expression of SIRT1 and FOXO1. Conclusion: These findings demonstrate for the first time the molecular cascade and related cell biology events involved in the mechanism by which HGF and bFGF derived from hADSCs improved ovarian function during natural aging via reduction of oxidative stress by activating the SIRT1/FOXO1 signaling pathway.

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“…Valvassori et al (2015) observed that BDNF treatment modulated the antioxidant enzymes, and protected the ouabain (OUA)-induced oxidative damage in the brain of rats. In addition, Takeda et al (2013) showed that BDNF protected human microvascular endothelial cells from the toxicity of TNF-α through the regulation of the PTEN/Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of parecoxib on rat primary astrocytes from oxidative stress induced by hydrogen peroxide

Ling

et al. 2016

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To investigate the protective effects of parecoxib from oxidative stress induced by hydrogen peroxide (H 2 O 2 ) in rat astrocytes in vitro. Methods: All experiments included 4 groups: (1) negative control (NC) group, without any treatment; (2) H 2 O 2 treatment group, 100 μmol/L H 2 O 2 treatment for 24 h; (3) and (4) parecoxib pretreatment groups, 80 and 160 μmol/L parecoxib treatment for 24 h, respectively, and then treated with 100 μmol/L H 2 O 2 . Several indices were investigated, and the expressions of Bax, Bcl-2, and brain-derived neurotrophic factor (BDNF) were quantified. Results: Compared to the NC group, exposure to H 2 O 2 resulted in significant morphological changes, which could be reversed by pretreatment of parecoxib. In addition, H 2 O 2 treatment led to loss of viability (P=0.026) and increased intracellular reactive oxygen species (ROS) levels (P<0.001), and induced apoptosis (P<0.01) in the primary astrocytes relative to the NC group. However, in the parecoxib pretreatment groups, all the above changes reversed significantly (P<0.05) as compared to the H 2 O 2 treatment group, and were nearly unchanged when compared to the NC group. Mechanical investigation showed that dysregulated Bax, Bcl-2, and BDNF could be implicated in these changes. Conclusions: Our results indicated that parecoxib provided a protective effect from oxidative stress induced by exposure to H 2 O 2 .

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Intracerebral Administration of BDNF Protects Rat Brain Against Oxidative Stress Induced by Ouabain in an Animal Model of Mania

Cited by 36 publications

References 71 publications

Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway

Protective effects of parecoxib on rat primary astrocytes from oxidative stress induced by hydrogen peroxide

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