Use of Phytoestrogens for the Treatment of Psychiatric Symptoms Associated with Menopause Transition

Menopause transition is recognized as a vulnerable period in women life to develop or aggravate symptoms of psychiatric disorders. Several treatments including antidepressants and hormonal restitution with estrogens have been suggested to ameliorate the symptoms. Also, in this period of life is frequent the use of other drugs to treat is also frequent the use of other drugs to treat comorbid pathologies that might even increase the risk of drug-drug interactions. Literature reports that some phytochemicals with estrogenic activity have beneficial effects during menopausal transition without collateral events. This chapter shows evidence about the use of phytoestrogens as an alternative therapy for the treatment of some psychiatric symptoms associated with the menopausal transition. Data derived from preclinical research related to the use of classical phytoestrogens (isoflavones), considering the beneficial effects, as well as adverse events, are discussed. Also, the use of polyphenols and organosulfurate compounds as an alternative for the treatment of anxiety- and depressive-like behavior as well as fibromyalgia is included. A narrative review was conducted using bibliography reporting the use of isoflavones (genistein, daidzein, equol), coumestans or lignans for the reduction of depressive-like or anxiety-like behavior. Furthermore, it is described if the use of this compounds impact in other signs of menopause, i.e. vasomotor and osteoporosis. In addition, due to the high frequency of comorbid pathologies as diabetes mellitus, dyslipidemia or metabolic syndrome with psychiatric disorders, the use of these phytochemicals is discussed

The Systemic Administration of the Histamine H1 Receptor Antagonist/Inverse Agonist Chlorpheniramine to Pregnant Rats Impairs the Development of Nigro-Striatal Dopaminergic Neurons

The dopaminergic and histaminergic systems are the first to appear during the development of the nervous system. Through the activation of H1 receptors (H1Rs), histamine increases neurogenesis of the cortical deep layers, while reducing the dopaminergic phenotype (cells immunoreactive to tyrosine hydroxylase, TH+) in embryo ventral mesencephalon. Although the function of histamine in neuronal differentiation has been studied, the role of H1Rs in neurogenesis has not been addressed. For this purpose, the H1R antagonist/inverse agonist chlorpheniramine was systemically administered (5 mg/kg, i.p.) to pregnant Wistar rats (gestational days 12–14, E12–14), and control and experimental embryos (E14 and E16) and pups (21-day-old) were evaluated for changes in nigro-striatal development. Western blot and immunohistochemistry determinations showed a significant increase in the dopaminergic markers’ TH and PITX3 in embryos from chlorpheniramine-treated rats at E16. Unexpectedly, 21-day-old pups from the chlorpheniramine-treated group, showed a significant reduction in TH immunoreactivity in the substantia nigra pars compacta and dorsal striatum. Furthermore, striatal dopamine content, evoked [3H]-dopamine release and methamphetamine-stimulated motor activity were significantly lower compared to the control group. These results indicate that H1R blockade at E14–E16 favors the differentiation of dopaminergic neurons, but hampers their migration, leading to a decrease in dopaminergic innervation of the striatum in post-natal life

Stress-dependent control of cytokine production in mast cells stimulated through FceRI and Toll-like 4 receptors: DOI: 10.14800/ics.881

Mast cells (MC) play an important role on allergic reactions triggered by the IgE/Antigen-dependent crosslinking of the high affinity IgE receptor (FceRI), and their participation on inflammatory innate immune responses triggered by Toll-like receptors (TLRs) has started to be documented. Physiological conditions such as stress exert a modulatory effect on allergic reactions since stress mediators activate signaling cascades that either interfere or potentiate the FceRI-dependent cytokine production. Recently, the effect of stress mediators on cytokine production induced after Toll-like receptors (TLRs) has started to be addressed in this cell type. In a recent paper, we analyzed the effects of stress induced by forced swimming (FS) on the MC-dependent production of Tumor Necrosis Factor (TNF) induced by a single intraperitoneal injection of bacterial lipopolysaccharide (LPS) in mice. FS provoked an immediate and transient inhibition of LPS-elicited TNF accumulation in peritoneum, which lasted around to 30 min. With the aim to identify the mediator of stress responsible for the inhibition, we first blocked catecholamine release from adrenal glands (by adrenalectomy) or nerve terminals (with DSP4 treatment). With these manipulations we observed an important increase on basal ip TNF levels and enhanced LPS-induced TNF release without any effect on stress-induced inhibitory effects. We then pre-treated animals with the glucocorticoid receptor antagonist mifepristone and did not observe any change on basal levels or stress-induced inhibition of TNF release. Finally, we administered an antagonist of acetylcholine receptors (mecamylamine) and observed an increase on basal levels of ip TNF values together with an important blockage of stress effects. Those results show for the first time that early MC-derived TNF secretion after Toll-like receptors is negatively controlled by adrenaline and transiently inhibited by the anti-inflammatory cholinergic reflex. Our results adds to the description of stress effects on MC activation and open new avenues in the research on the control of chronic inflammatory reactions associated with long term MC-dependent cytokine secretion

Wistar-Kyoto Female Rats Are More Susceptible to Develop Sugar Binging: A Comparison with Wistar Rats

The hedonic component of the feeding behavior involves the mesolimbic reward system and resembles addictions. Nowadays, the excessive consumption of sucrose is considered addictive. The Wistar-Kyoto (WKY) rat strain is prone to develop anxiety and addiction-like behavior; nevertheless, a lack of information regarding their vulnerability to develop sugar binging-like behavior (SBLB) and how it affects the reward system persist. Therefore, the first aim of the present study was to compare the different predisposition of two rat strains, Wistar (W) and WKY to develop the SBLB in female and male rats. Also, we studied if the SBLB-inducing protocol produces changes in anxiety-like behavior using the plus-maze test (PMT) and, analyzed serotonin (5-HT) and noradrenaline (NA) concentrations in brain areas related to anxiety and ingestive behavior (brain stem, hypothalamus, nucleus accumbens, and amygdala). Finally, we evaluated whether fluoxetine, a drug that has been effective in reducing the binge-eating frequency, body weight, and severity of binge eating disorder, could also block this behavior. Briefly, WKY and W female rats were exposed to 30% sucrose solution (2 h, 3 days/week for 4 weeks), and fed up ad libitum. PMT was performed between the last two test periods. Immediately after the last test where sucrose access was available, rats were decapitated and brain areas extracted for high-performance liquid chromatography analysis. The results showed that both W and WKY female and male rats developed the SBLB. WKY rats consumed more calories and ingested a bigger amount of sucrose solution than their W counterpart. This behavior was reversed by using fluoxetine, rats exposed to the SBLB-inducing protocol presented a rebound effect during the washout period. On female rats, the SBLB-inducing protocol induced changes in NA concentrations on WKY, but not on W rats. No changes were found in 5-HT levels. Finally, animals that developed SBLB showed increased anxiety-like behavior in the PMT. In conclusion, WKY female rats can be considered as a more susceptible rat strain to develop SBLB

Table_1_Stress hyper-reactivity increases vulnerability to developing binge-type eating and associated anxiety-like behavior; comparison between Wistar-Kyoto and Sprague-Dawley rats.docx

IntroductionBinge eating disorder (BED) is a widespread eating disorder that primarily affects women worldwide, and it is characterized by the presence of binge eating episodes and the absence of any compensatory behavior to prevent weight gain. BED presents elevated comorbidity with other psychiatric disorders, such as anxiety, and it has been suggested that stress sensibility could be a vulnerability factor for the development of BED and the associated anxiety comorbidity. In this study, we aim to investigate whether the Wistar-Kyoto rat strain (WKY), which has a stress hyper-reactive phenotype, could develop both binge-type eating and anxiety-like behaviors simultaneously. We also aim to compare its vulnerability to developing both behaviors with the Sprague Dawley rat strain (SD), a rat strain commonly used in binge-eating models.MethodsWKY and SD rats were subjected to the model of intermittent access to palatable food (sucrose solution 30% or shortening) without calorie restriction or stress exposure. We evaluated and compared the development of binge-type eating behavior, anxiety-like behavior, and serum corticosterone variation as an index of the stress response in both rat strains.ResultsWKY rats presented a higher percentage of binge-type eaters and required less time to develop binge-type eating behavior than SD rats. The WKY eating pattern emulated a binge-eating episode regardless of the palatable food. Although the development of sucrose binge-type eating was similar between strains, WKY developed more easily the shortening binge-type eating than SD and was more susceptible to developing anxiety-like behavior. Additionally, sucrose binge eating seems to differentially affect both strains’ hypothalamic-pituitary-adrenal (HPA) axis response to stress since it facilitated its response in SD and blunted it in WKY.DiscussionOur results show that high-stress sensitive phenotype is a common vulnerability factor for the development of binge-type eating and anxiety-like behavior. Regardless of the macronutrient composition of the palatable food, WKY is susceptible to developing a binge-type eating behavior and is more susceptible than SD to developing anxiety-like behavior simultaneously. In conclusion, results showed that a hyper-reactive stress phenotype predisposes the development of binge-type eating behavior and anxiety-like behavior in the absence of calorie restriction and stress exposure.</p