17β-Estradiol augments the neuroprotective effect of agomelatine in depressive- and anxiety-like behaviors in ovariectomized rats

Wang

et al. 2022

Front. Aging Neurosci.

PurposeThis study aimed to examine whether aerobic exercise exerts mood-modulating effects through an estrogen signaling mechanism.MethodThe experiment was divided into two parts. The first part is to compare the three modeling methods to obtain the most obvious method of depression-like phenotype for further study in the second part. The first part of ovariectomized rats (age, 13 weeks) was tested when rats were 14 or 22 weeks old or in the sixth week after 3 weeks of chronic restraint stress. The second part was to treat the animals with the most obvious depression-like phenotype in different ways, placebo treatment or estradiol (E2) replacement therapy was administered, aerobic training, or estrogen receptor antagonist treatment. The cognitive (Barnes maze and 3-chamber social tests), anxiety-like (open-field and elevated plus maze tests) and depression-like (sucrose preference and forced swim tests) behaviors of rats in both parts were analyzed to study the effects of estrogen depletion and aerobic exercise.ResultsRats did not develop depressive symptoms immediately after ovariectomy, however, the symptoms became more pronounced with a gradual decrease in ovarian hormone levels. Compared with the placebo or control groups, the exercise and E2 groups showed improved performance in all behavioral test tasks, and the antidepressant effects of aerobic exercise were comparable to those of estrogen. Moreover, the estrogen receptor antagonist has markedly inhibited the antidepressant effects of aerobic exercise.ConclusionEstrogen receptors may mediate the antidepressant effects of aerobic exercise. In addition, an increasingly fragile ovarian hormonal environment may underlies chronic restraint stress-induced depression.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estrogen receptors mediate the antidepressant effects of aerobic exercise: A possible new mechanism

Wang

et al. 2022

Front. Aging Neurosci.

Behavioural Pharmacology

“…On the other hand, it has been suggested that the use of a combined therapy, estradiol plus antidepressant, could be advantageous for the treatment of depression in perimenopausal or menopausal women (Vega-Rivera et al, 2016). Some clinical studies suggest that estrogen may enhance the effect of other antidepressants (Estrada-Camarena et al, 2004), such as selective serotonin reuptake inhibitors (SSRIs) (Benmansour et al, 2016b), agomelatine (El-Khatib et al, 2020), escitalopram (Ibrahim et al, 2016), fluoxetine (Récamier-Carballo et al, 2012), and topiramate (Molina-Hernández et al, 2014). However, other studies have reported that estradiol can block the antidepressant effect of some antidepressants such as sertraline, desipramine, or fluvoxamine (Shah and Frazer, 2014;Benmansour et al, 2016aBenmansour et al, , 2016b.…”

Section: Introductionmentioning

confidence: 99%

Estradiol enhances the mirtazapine effects on the expression of cocaine-induced locomotor sensitization in female rats

Barbosa-Méndez,

Salazar-Juárez

2023

Epidemiological studies have mentioned that cocaine use disorder (CUD) has increased in the last decade among women; these show endocrine and reproductive disorders and a high propensity to stress and depression disorders. Mirtazapine—a tetracyclic antidepressant—decreases cocaine-induced locomotor activity and locomotor sensitization in male rats. The objective of this study was to evaluate if estradiol alters the efficacy of mirtazapine to decrease cocaine-induced locomotor activity in sham and ovariectomized female rats. Three hundred and twenty adult female Wistar rats were assigned to three experimental protocols. For experiments, 1–3, female rats were daily dosed with 10 mg/kg of cocaine during the 10 days of induction and expression of locomotor sensitization. During drug withdrawal (30 days), cocaine was withdrawn and the groups received daily mirtazapine, estradiol, or saline. In addition, the females underwent sham or ovariectomy surgery. Tamoxifen was administered during the antagonism phase. After each administration, locomotor activity for each animal was recorded for 30 min in activity chambers. The dosage of mirtazapine reduces estradiol-induced enhancement in cocaine-dependent locomotor activity during the expression of locomotor sensitization in sham and ovariectomized female rats. As well as they showed that estradiol co-dosed with mirtazapine enhances the efficacy of mirtazapine to decrease cocaine-induced locomotor activity. Finally, tamoxifen enhanced the estradiol and mirtazapine-induced decrease in the cocaine motor effect in female rats. Mirtazapine may be considered an effective therapeutic option for the treatment of CUD in women, even in those who are on hormonal treatment or antidepressant therapy with estradiol.

“…Increasing evidences show that BDNF exerts an antidepressive effect mainly by promoting neuronal proliferation ( 25 ). The decreased level of hippocampal BDNF in a rat model of depression was found to inhibit neuronal proliferation ( 26 ). Moreover, central inflammation was associated with reduced BDNF, as confirmed by the series of studies on animals and humans ( 27 , 28 ).…”

Section: Introductionmentioning

confidence: 99%

Prevotella histicola Mitigated Estrogen Deficiency-Induced Depression via Gut Microbiota-Dependent Modulation of Inflammation in Ovariectomized Mice

Huang

Liu

et al. 2022

Front. Nutr.

BackgroundEstrogen deficiency-induced depression is closely associated with an imbalance in intestinal microbiota and inflammation. Prevotella histicola (P. histicola), an emerging probiotic, apparently improves inflammatory responses. This study aims to verify the antidepressant-like effects of P. histicola and clarify its potential mechanisms.MethodsMice were treated with P. histicola and cohousing after ovariectomy (OVX). The changes in depression-like behaviors among mice were examined by behavioral tasks, and alterations in the microbiota were detected through 16S rRNA sequencing. Changes in neuronal injury, protein synthesis, inflammatory factors, intestinal permeability, and nerve proliferation were observed by H&E, Nissl staining, qRT-PCR, western blotting, and immunofluorescence.ResultsP. histicola significantly reduces depression-like behaviors and neuronal damage induced by estrogen deficiency. Additionally, P. histicola significantly increases the abundance of intestinal flora, especially Lactobacillus and Akkermansia. Meanwhile, the cohoused mice also had a better emotional state and neutral structure compared with OVX mice. P. histicola was also found to upregulate tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the ileum and colon and reduce the levels of inflammatory factors VCAM, MCP-1, IL-6, IL-8, and TNF-α, mainly in the ileum, colon, and decrease the expression of COX-2, TLR4, Myd88, JNK, MCP-1, IL-6, IL-8, and TNF-α in the hippocampus. Moreover, significant downregulation of apoptosis (caspase-3 and caspase-8) and upregulation of neurotrophic factors (BDNF and Ki-67) were observed after P. histicola treatment.ConclusionOur data show that P. histicola significantly mitigates depression of OVX mice through improvement in intestinal microbiota to repair intestinal leakage and inhibit central inflammation to promote the expression of BDNF for hippocampal neurogenesis. P. histicola may be therapeutically beneficial for PMD.