Long-term ovariectomy increases anxiety- and despair-like behaviors associated with lower Fos immunoreactivity in the lateral septal nucleus in rats

Puga-Olguín, Abraham; Rodríguez‐Landa, Juan Francisco; Rovirosa-Hernández, María de Jesús; Germán-Ponciano, León Jesús; Caba, Mario; Meza, Enrique; Guillén-Ruiz, Gabriel; Olmos-Vázquez, Oscar Jerónimo

doi:10.1016/j.bbr.2018.12.017

Cited by 50 publications

(41 citation statements)

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“…We found that chronic OVX induced depressive-like behaviors with decreased immobility time in the FST and decreased latency time in the NSFT, in line with a previous study that OVX developed depressive-like behaviors at more than 6 weeks [19]. The OVX model was successfully built, as evidenced by the increased bodyweight, decreased uterine weight, and decreased estrogen level.…”

Section: Discussionsupporting

confidence: 89%

Vitamin D and 17β-estradiol upregulate each other's receptors and regulating the AMPK/NF-κB pathway to relieve depressive-like behaviors in female ovariectomized rats

Zhang

Guo

Wang

et al. 2019

Preprint

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Background: A deficiency of vitamin D (VD) or 17β-estradiol (E2) is associated with increased risk of mood disorders such as depression in menopausal females, but the mechanism underlying is still elusive. The present study aims to evaluate whether vitamin D and 17β-estradiol could relieve a depressive-like state through neuroinflammatory regulation in ovariectomized (OVX) rats. Methods: Female SD rats were randomly divided into four groups, namely, control (SHAM), OVX, OVX+VD, and OVX+E2. The treatment procedure was performed for 10 weeks until sacrifice. Results: The chronic administration of vitamin D and 17β-estradiol showed anti-depressive-like activity in the OVX rats. Additionally, vitamin D and 17β-estradiol upregulated each other's receptors, including VDR, ERα, and ERβ in the hippocampus of OVX rats. Vitamin D and 17β-estradiol showed neuroprotective effects by decreasing OVX-induced apoptosis and neuronal damage, regulating the AMPK/NF-κB signaling pathway, and reducing the proinflammatory cytokines (IL-1β, IL-6, and TNFα), as well as iNOS and COX-2 in the hippocampus of OVX rats. Conclusions: The present study demonstrated that vitamin D and 17β-estradiol could upregulate each other's receptors and regulate the AMPK/NF-κB pathway to relieve the OVX-induced depressive-like state. The results should stimulate translational research towards the vitamin D potential for prevention or treatment of menopause-related depression.

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Section: Discussionsupporting

confidence: 89%

Vitamin D and 17β-estradiol upregulate each other's receptors and regulating the AMPK/NF-κB pathway to relieve depressive-like behaviors in female ovariectomized rats

Zhang

Guo

Wang

et al. 2019

Preprint

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“…Such changes can negatively affect memory processes (McLaughlin, Bimonte-Nelson, Neisewander, & Conrad, 2008), immune function (Baeza, de Castro, Giménez-Llort, & de la Fuente, 2010), and cardiovascular function (McGregor et al, 2014). Additionally, an increase in anxiety-and depression-like behavior is detected several weeks post-OVX (Picazo et al, 2006;Puga-Olguín et al, 2019). These findings validate the utility of the rat model of ltOVX for exploring physiological and emotional changes associated with ovarian failure or hysterectomy, based on the criteria of the Stages of Reproductive Aging Workshop (STRAW) in women (Harlow et al, 2012).…”

Section: Introductionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

“…Beginning at one-week post-OVX, female rats exhibit anxiety-like behavior compared with females in proestrus-estrus (Puga-Olguín et al, 2019), an ovarian cycle phase that is characterized by high concentrations of steroid hormones. At eight weeks post-OVX, depres-sion-like behavior is observed in the forced swim test (Puga-Olguín et al, 2019). Based on the STRAW criteria, these time-dependent effects of OVX may be related to hormonal changes that occur during the early stage (e.g., an increase in follicle-stimulating hormone levels and decrease in inhibin A and estradiol levels) and late stage (e.g., permanent very low concentrations of inhibin A and estradiol) of menopause (Harlow et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Actions of progesterone on depression-like behavior in a model of surgical menopause are mediated by GABAA receptors

et al. 2020

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Introduction. In rats, long-term ovariectomy results in low concentrations of steroid hormones and reproduces anxiety- and depression-like behavior after surgical menopause in women. Progesterone produces antidepressant-like effects two weeks post-ovariectomy (i.e., early post-ovariectomy) through actions on γ-aminobutyric acid-A (GABAA) receptors, but its antidepressant-like effects and mechanism of action in rats eight weeks post-ovariectomy (i.e., late post-ovariectomy, considered a model of surgical menopause) remain unknown. Objective. To explore the antidepressant-like effects of progesterone and the participation of GABAA receptors in rats eight weeks post-ovariectomy. Method. Long-term ovariectomized female Wistar rats were treated sub-acutely with vehicle or progesterone (.5, 1, and 2 mg/kg) and subjected to the open field and forced swim tests, and behavior was compared with cycling or fluoxetine-treated rats. The rats were then pretreated with picrotoxin (1 mg/kg) followed by progesterone (1 mg/kg) to explore the role of GABAA receptors in long-term-induced depression-like behavior. Results. Long-term ovariectomized rats exhibited depression-like behavior in the forced swim test compared with intact rats, an effect that was not observed in progesterone- and fluoxetine-treated long-term ovariectomized rats. These effects were not attributable to psychomotor alterations. In the open field test, the time spent rearing and grooming was lower in ovariectomized rats compared with intact rats, which was not observed in progesterone- and fluoxetine-treated rats. Picrotoxin blocked the effects of progesterone in both behavioral tests. Discussion and conclusion. These results indicated that sub-acute progesterone treatment reduced depression-like behavior through actions on GABAA receptors in a rat model of surgical menopause.

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“…** p < 0.01 compared to Sham group. + p < 0.05, ++ p < 0.01 compared to OVX group behavioral changes that at least 6 weeks are needed for the animal to develop depression-like behaviors [22], the present study evaluated the behaviors and biochemical factors 10 weeks after OVX surgery to guarantee the animal model was successfully developed and PUFA was sufficiently supplemented. The experimental procedure succeeded as evidenced by the increased body weight and decreased uterine weight and estrogen levels.…”

Section: Discussionmentioning

confidence: 98%

Antidepressant activity of ω-3 polyunsaturated fatty acids in ovariectomized rats: role of neuroinflammation and microglial polarization

Song

Zhang

et al. 2020

Lipids Health Dis

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Background: Menopause predisposes individuals to affective disorders, such as depression, which is tightly related to neuroinflammation. While the neuroinflammatory condition has been demonstrated in ovariectomized (OVX) rodents, there is limited evidence concerning microglial polarization, a key process in brain immune activation, in menopause-related brain. Methods: Therefore, the present study aims to evaluate the polarized microglia in long-term OVX rats and we further explored whether supplementation of ω-3 polyunsaturated fatty acids (PUFA), the pleiotropic bioactive nutrient, is effective in the neurobehavioral changes caused by OVX. Results: Our data showed that OVX-induced anxiety and depression-like behaviors in rats, accompanied with increased neural apoptosis and microglial activation in the hippocampus. Additionally, OVX enhanced proinflammatory cytokines expression and suppressed the expression of anti-inflammatory cytokine, IL-10. Correspondingly, OVX reinforced NFκB signaling and shifted the microglia from immunoregulatory M2 phenotype to proinflammatory M1 phenotype. Meanwhile, daily supplementation with PUFA suppressed microglial M1 polarization and potentiated M2 polarization in OVX rats. In parallel, PUFA also exerted antidepressant and neuroprotective activities, accompanied with neuroimmune-modulating actions. Conclusion: Collectively, the present study firstly demonstrated the disturbed microglial polarization in the OVX brain and provide novel evidence showing the association between the antidepressant actions of PUFA and the restraint neuroinflammatory progression.

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Long-term ovariectomy increases anxiety- and despair-like behaviors associated with lower Fos immunoreactivity in the lateral septal nucleus in rats

Cited by 50 publications

References 85 publications

Vitamin D and 17β-estradiol upregulate each other's receptors and regulating the AMPK/NF-κB pathway to relieve depressive-like behaviors in female ovariectomized rats

Vitamin D and 17β-estradiol upregulate each other's receptors and regulating the AMPK/NF-κB pathway to relieve depressive-like behaviors in female ovariectomized rats

Actions of progesterone on depression-like behavior in a model of surgical menopause are mediated by GABAA receptors

Antidepressant activity of ω-3 polyunsaturated fatty acids in ovariectomized rats: role of neuroinflammation and microglial polarization

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