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Menopausal women may experience symptoms of depression, sometimes even progressing clinical depression requiring treatment to improve quality of life. While varying levels of estrogen in perimenopause may contribute to an increased biological vulnerability to mood disturbances, the effectiveness of estrogen replacement therapy (ERT) in the relief of depressive symptoms remains controversial. Menopausal depression has a complex, multifactorial etiology, that has limited the identification of optimal treatment strategies for the management of this psychiatric complaint. Nevertheless, clinical evidence increasingly supports the notion that estrogen exerts neuroprotective effects on brain structures related to mood regulation. Indeed, research using preclinical animal models continues to improve our understanding of menopause and the effectiveness of ERT and other substances at treating depression-like behaviors. However, questions regarding the efficacy of ERT in perimenopause have been raised. These questions may be answered by further investigation using specific animal models of reduced ovarian function. This review compares and discusses the advantages and pitfalls of different models emulating the menopausal stages and their relationship with the onset of depressive-like signs, as well as the efficacy and mechanisms of conventional and novel ERTs in treating depressive-like behavior. Ovariectomized young rats, middle-to-old aged intact rats, and females treated with reprotoxics have all been used as models of menopause, with stages ranging from surgical menopause to perimenopause. Additionally, this manuscript discusses the impact of organistic and therapeutic variables that may improve or reduce the antidepressant response of females to ERT. Findings from these models have revealed the complexity of the dynamic changes occurring in brain function during menopausal transition, reinforcing the idea that the best approach is timely intervention considering the opportunity window, in addition to the careful selection of treatment according to the presence or absence of reproductive tissue. Additionally, data from animal models has yielded evidence to support new promising estrogens that could be considered as ERTs with antidepressant properties and actions in endocrine situations in which traditional ERTs are not effective.

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BACKGROUND: The flavonoid chrysin produces rapid and long-lasting anxiolytic- and antidepressant-like effects in rats. However, it is not known whether low and high doses of chrysin produce differential anti-immobility effects through the Gamma-Aminobutyric Acid sub-type A (GABAA) receptor. The goal of this work was therefore to compare low and high doses of chrysin for their effects on depression-like behavior in a longitudinal study. Moreover, chrysin was compared with the serotonergic fluoxetine and Gamma-Aminobutyric Acid (GABA)ergic allopregnanolone, and its involvement with the GABAA receptor after chronic treatment was also investigated. METHODS: Male Wistar rats were assigned to five groups (n = 8 each): vehicle, 1 mg/kg chrysin, 5 mg/kg chrysin, 1 mg/kg fluoxetine, and 1 mg/kg allopregnanolone. In the first experiment, treatments were injected daily and the effects on locomotor activity and the forced swim test were evaluated at 0, 1, 14, and 28 days of treatment, and 48 h after the final treatment. In the second experiment, similar groups were treated for 28 days with injection of 1 mg/kg picrotoxin to investigate the role of the GABAA receptor. Depending on the experimental design, one- and two-way analysis of variance (ANOVA) tests were used for statistical analysis, with p < 0.05 set as the criteria for significance. RESULTS: In both experiments, the treatments did not alter locomotor activity. However, low and high doses of chrysin, allopregnanolone, and fluoxetine gradually produced antidepressant-like effects in the forced swim test, and maintained this effect for 48 h post-treatment, except with low dose chrysin. Picrotoxin blocked the antidepressant-like effects produced by low dose chrysin, but did not affect those produced by high dose chrysin, allopregnanolone, or fluoxetine. CONCLUSIONS: The differential antidepressant-like effects caused by low and high doses of chrysin are time-dependent. Low dose chrysin produces a rapid antidepressant-like effect, whereas high dose chrysin produces a delayed but sustained the effect, even 48 h after withdrawal. The effect with high dose chrysin was similar to that observed with allopregnanolone and fluoxetine. The mechanism for the antidepressant-like effect of low chrysin appears to be GABAergic, whereas the effect of high dose chrysin may involve other neurotransmission and neuromodulation systems related to the serotonergic system.

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ETHNOPHARMACOLOGICAL IMPORTANCE: Cucurbita ficifolia Bouché fruit is widely used in Mexican traditional medicine to treat type 2 diabetes (T2D) because it has been attributed with antioxidant and hypoglycemic properties in different experimental models and T2D patients. An imbalance in physiological glutathione (GSH) concentrations increases the susceptibility to developing complications associated with oxidative stress in T2D patients. AIM OF THE STUDY: To investigate the effect of C. ficifolia on the antioxidant properties of GSH, general health measurements, and biochemical parameters in a Mexican rural population, and to evaluate the changes in socio-affective scores of patients due to improvement in T2D. MATERIALS AND METHODS: Twenty-seven women diagnosed with T2D with poor glycemic control volunteered and were divided into two groups: C. ficifolia (0.5 g/kg of fresh pulp weight) with hypoglycemic pharmacotherapy, and another group with only hypoglycemic pharmacotherapy, for 12 weeks. We evaluated the effect of the fresh pulp of C. ficifolia on body mass index, blood pressure, glucose, glycosylated hemoglobin, cholesterol, triglycerides, and GSH. Expanding the study, we evaluated the quality of life, anxiety, and depression scores before and after the intervention. RESULTS: Treatment with the fresh pulp of C. ficifolia for 12 weeks reduced glycosylated hemoglobin, similar to the hypoglycemic pharmacotherapy group, and significantly increased GSH concentrations. The patients' moods did not change despite increased GSH concentrations and improved T2D control. CONCLUSIONS: The increased GSH concentrations due to the consumption of fresh pulp of C. ficifolia could help to protect against oxidative stress and extend therapeutic benefits in addition to the usual hypoglycemic drugs in patients with T2D.

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In tradition al Mexican medicine, plants from the Montanoa genus, family Asteraceae ( Montanoa tomentosa , Montanoa grandiflora , and Montanoa frutescens ) have been used to induce labor owing to their uterotonic properties like those produced by oxytocin (OXT). However, w hether infusions of these plants can activate hypothalamic OXT - producing neurons is unknown. To test this possibility, five independent groups of Wistar rats (n=4) were included: intact, vehicle, and three groups that received 50 mg/kg p.o. of M. tomentosa , M. grandiflora , and M. frutescens infusions, respectively. Ninety min after treatment, the brains were obtained and processed using double - labeled immunohistochemistry for Fos protein and oxytocin (Fos/OXT - ir). Rats that received Montanoa infusions had s ignificantly greater number of Fos/OXT - ir cells in the paraventricular (PVN) and supraoptic (SON) nuclei, with respect to intact and vehicle groups. These findings demonstrate that Montanoa infusions activated OXT neurons, an effect that may be related to the reported pharmacological properties.

En la medicina tradicional mexicana, plantas del género Montanoa , familia Asteraceae ( Montanoa tomentosa , Montanoa grandiflora y Montanoa frutescens ), se han utilizado para inducir el parto debido a sus propiedades uterotónicas, aparentemente similares a las producidas por la hormona oxitocina (OXT). Sin embargo, se desconoce si las infusiones de estas plantas pueden activar neuronas hipotalámicas productoras de OXT. Para probar esta posibilidad, se incluyeron cinco grupos independientes (n=4): intacto, vehículo y tres grupos que recibieron 50 mg/kg p.o. de infusiones de M. tomentosa , M. grandiflora , y M. frute scens , respectivamente. Noventa minutos después del tratamiento, los cerebros fueron obtenidos y procesados por doble marcaje de inmunohistoquímica para la proteína Fos y oxitocina (Fos/OXT - ir). Las ratas que recibieron infusiones de Montanoa aumentaron si gnificativamente el número de células Fos/OXT - ir en los núcleos paraventricular (PVN) y supraóptico (SON), respecto a los grupos intacto y vehículo. Estos hallazgos demuestran que las infusiones de Montanoa activan neuronas de OXT, lo que podría estar rela cionado con sus propiedades farmacológicas

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Hyperammonemia is characterized by the excessive accumulation of ammonia in the body as a result of the loss of liver detoxification, leading to the development of hepatic encephalopathy (HE). These metabolic alterations carry cognitive and motor deficits and cause neuronal damage, with no effective treatment at present. In this study, we aimed to evaluate the effect of two subacute oral administrations of flaxseed oil (0.26 and 0.52 mL/kg) on short- and long-term memory, visuospatial memory, locomotor activity, motor coordination, and the neuronal morphology of the prefrontal cortex (PFC) via tests on Wistar rats with hyperammonemia. The goal was to identify its role in the regulation of cerebral edema, without liver damage causing cerebral failure. In contrast with an ammonium-rich diet, flaxseed oil and normal foods did not cause cognitive impairment or motor alterations, as evidenced in the short-term and visuospatial memory tests. Furthermore, the flaxseed oil treatment maintained a regular neuronal morphology of the prefrontal cortex, which represents a neuroprotective effect. We conclude that the oral administration of flaxseed oil prevents cognitive and motor impairments as well as neuronal alterations in rats with hyperammonemia, which supports the potential use of this oil to ameliorate the changes that occur in hepatic encephalopathy.

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Tryptophan hydroxylase (TPH) catalyzes the rate-limiting step of serotonin synthesis. TPH2 is the brain-specific isoform of this enzyme, and genetic variations in the TPH2 gene have been shown to impact its transcription and enzymatic activity and are associated with mood disorders. In this study we focused on the rs4570625 (-703G/T) single nucleotide polymorphism of TPH2 gene. By using conventional polymerase chain reaction (PCR), we examined the effect of this polymorphism on stress, anxiety, and depression symptoms as well as quality of life, evaluated based on the Holmes-Rahe Inventory, the Beck Anxiety Inventory, the Beck Depression Inventory, and the World Health Organization Quality of Life - Short Version, respectively. We found that individuals with the homozygous recessive T/T genotype had lower stress and depression scores. In addition, the quality of life in the psychological health domain was better in males with the T/T genotype. These results suggest that T/T genotype could decrease the susceptibility to developing stress and depression in the Mexican population without a diagnosis for an emotional disorder.

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Metabolic syndrome includes a set of metabolic alterations associated with overweight and obesity. The criteria for its diagnosis are heterogeneous, and there have been few studies about prevalence in the pediatric population. The aim of this study was to describe how the estimated prevalence of metabolic syndrome varies by International Diabetes Federation (IDF) vs. National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP) criteria. We conducted a cross-sectional study in which anthropometric information, triglyceride, cholesterol, glycemia, and insulin levels, among others, were collected. We compared the group potentially misclassified by IDF with the group classified without metabolic syndrome by NCEP-ATP with respect to weight status and biomarkers. Statistical analysis included linear regression, Mann-Whitney U test, Fisher´s exact test, and odds ratio calculation. The IDF criteria missed the association with obesity, although the undetected group differed significantly from the nonmetabolic syndrome group in terms of IBM and weight. The associated biomarkers were ultrasensitive C-reactive protein (Hs-CRP), alanine aminotransferase (ALT) enzyme, insulin, triglycerides, and high-density lipoprotein (HDL) cholesterol. Waist circumference was the parameter with the strongest association for presenting metabolic syndrome, with an odds ratio of 18.33. The results of this study showed the estimated prevalence of MS varies by criteria, due to cutoff points, and how the high prevalence of MS strongly associated with obesity.

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Women have a high susceptibility to the negative effects of stress. Hormonal changes experienced throughout their reproductive life partially contribute to a higher incidence of anxiety and depression symptoms, particularly, during natural or surgical menopause. In preclinical research, the flavonoid chrysin (5,7-dihydroxyflavone) exerts anxiolytic- and anti-despair-like effects; however, it is unknown whether chrysin exerts a protective effect against the behavioral changes produced by acute stress on locomotor activity and behavioral despair in rats at 12-weeks post-ovariectomy. Ovariectomized female Wistar rats were assigned to eight groups: vehicle group (10% DMSO), three groups with chrysin and three groups with the same dose of allopregnanolone (0.5, 1, and 2 mg/kg), and one group with diazepam (2 mg/kg). The treatments were administered for seven consecutive days and the effects were evaluated in the locomotor activity and swimming tests. Chrysin (2 mg/kg) increased the latency to first immobility and decreased the total immobility time in the swimming test as the reference drugs allopregnanolone and diazepam (2 mg/kg); while locomotor activity prevented the behavioral changes produced by swimming. In conclusion, chrysin exerts a protective effect against the behavioral changes induced by acute stress, similarly to the neurosteroid allopregnanolone and the benzodiazepine diazepam in rats subjected to a surgical menopause model.

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Depressive disorders are among the most disabling diseases experienced around the world, and their incidence has significantly increased over the last few decades due to multiple environmental, social, and biological factors. The search for new pharmacological alternatives to treat depression is a global priority. In preclinical research, molecules obtained from plants, such as flavonoids, have shown promising antidepressant-like properties through several mechanisms of action that have not been fully elucidated, including crossing of the blood brain barrier (BBB). This review will focus on discussing the main findings related to the participation of the serotonergic system and brain-derived neurotrophic factor (BDNF) on the antidepressant-like effect of some flavonoids reported by behavioral, neurochemical, and molecular studies. In this sense, evidence shows that depressive individuals have low levels of serotonin and BDNF, while flavonoids can reverse it. Finally, the elucidation of the mechanism used by flavonoids to modulate serotonin and BDNF will contribute to our understanding of the neurobiological bases underlying the antidepressant-like effects produced by these natural compounds.

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Chrysin (5,7-dihydroxyflavone) is a flavonoid isolated from plants, such as Passiflora coerulea, Passiflora incarnata, and Matricaria chamomilla. This natural molecule exerts diverse pharmacological effects, which includes antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and anti-apoptotic effects. Additionally, in brain structures, such as the hippocampus, prefrontal cortex, raphe nucleus, and striatum, involved in the physiopathology of anxiety and depression disorders, several neuropharmacological activities, including the activation of neurotransmitter systems (GABAergic, serotonergic, dopaminergic, and noradrenergic), neurotrophic factors, such as brain-derived neurotrophic factor and the nerve growth factor, and some signaling pathways are affected. The results showed that the anxiolytic and antidepressant-like effects of chrysin occurs through its interaction with specific neurotransmitter systems, principally the GABAergic and the serotonergic, and activation of other neurotrophic factors. However, it is not possible to discard the antioxidant and anti-inflammatory activities of chrysin while producing its anxiolytic- and antidepressant-like effects. Although these results have been obtained principally from pre-clinical research, they consistently demonstrate the potential therapeutic use of flavonoid chrysin as an anxiolytic and antidepressant agent. Therefore, this flavonoid could be considered as a promising novel therapy for anxiety and depression disorders.

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Epilepsy is a chronic neurological disorder that lacks a cure. The use of plant-derived antioxidant molecules such as those contained in turmeric powder and resveratrol may produce short-term anticonvulsant effects. A total of 42 three-month-old male Wistar rats were divided into six groups (n = 7 in each group): Vehicle (purified water), turmeric (150 and 300 mg/kg, respectively), and resveratrol (30 and 60 mg/kg, respectively), administered per os (p.o.) every 24 h for 35 days. Carbamazepine (300 mg/kg/5 days) was used as a pharmacological control for anticonvulsant activity. At the end of the treatment, status epilepticus was induced using the lithium-pilocarpine model [3 mEq/kg, intraperitoneally (i.p.) and 30 mg/kg subcutaneously (s.c.), respectively]. Seizures were evaluated using the Racine scale. The 300 mg/kg of turmeric and 60 mg/kg of resveratrol groups had an increased latency to the first generalized seizure. The groups treated with 150 and 300 mg/kg of turmeric and 60 mg/kg of resveratrol also had an increased latency to status epilepticus and a decreased number of generalized seizures compared to the vehicle group. The chronic administration of turmeric and resveratrol exerts anticonvulsant effects without producing kidney or liver damage. This suggests that both of these natural products of plant origin could work as adjuvants in the treatment of epilepsy.

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OBJECTIVE: To evaluate the association between body mass index (BMI) and performance of executive functions (EFs) in girls and boys with 9- and 10-year-old schoolchildren with moderate- to vigorous-intensity physical activity (MVPA) and sedentary behaviour. METHODS: A total of 120 schoolchildren (61 girls and 59 boys) were evaluated anthropometrically. The MVPA was evaluated with a self-report questionnaire. EFs were measured using a neuropsychological battery of Executive Functions and Frontal Lobes-2 (BANFE-2). RESULTS: A high BMI was associated with longer delay in completing inhibitory control tests (p = 0.00, rp  = 0.32) and working memory (p = 0.00, rp  = 0.26). We observed correlations in time (p = 0.00, rp  = -0.43) and hits (p = 0.04, rp  = -0.27) of self-directed signalling test in boys; and girls in alphabetical words order (p = 0.00, rp  = -0.39). Active normal weight schoolchildren (ANw) performed better by successfully completed the working memory tasks (H = 26.97, p = 0.00) than sedentary schoolchildren with overweight and obesity. In addition, overweight-active schoolchildren (AOw) showed better performance on working memory tests in time (p = 0.00) and hits (p = 0.01) than their sedentary peers. Multiple linear regression analysis revealed a significant association between BMI and EFs scores (F = 2.41, df = 98, p = 0.001). CONCLUSIONS: EFs are affected by a high BMI and sedentary behaviour in school children. Boys and girls reflected differences to solve the same challenges. The MVPA has a positive effect on executive control skills mainly in overweight children.

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Caffeine is a commonly used stimulant of the central nervous system that reduces fatigue, increases alertness, and exerts positive effects on emotion through actions on various brain structures. High doses of caffeine can cause headaches, heart palpitations, hyperactivity, and anxiety symptoms. Consequently, reducing the consumption of stimulant substances, such as sugar and caffeine, is proposed to ameliorate symptoms of premenstrual syndrome in women. The administration of steroid hormones has been suggested to modulate the effects of caffeine, but unknown is whether endogenous hormone variations during the estrous cycle modulate the pharmacological effects of caffeine. The present study evaluated the effects of caffeine (10, 20, and 40 mg/kg) during metestrus-diestrus and proestrus-estrus of the ovarian cycle in rats on anxiety-like behavior using the elevated plus maze and light/dark box. During metestrus-diestrus, all doses of caffeine increased anxiety-like behavior, indicated by the main variables in both behavioral tests (i.e., higher Anxiety Index and lower percent time spent on the open arms in the elevated plus maze and less time spent in the light compartment in the light/dark box). During proestrus-estrus, only 20 and 40 mg/kg caffeine increased these parameters of anxiety-like behavior, albeit only slightly. In conclusion, caffeine increased anxiety-like behaviors in metestrus-diestrus, with an attenuation of these effects of lower doses of caffeine in proestrus-estrus. These effects that were observed in metestrus-diestrus and proestrus-estrus may be associated with low and high concentrations of steroid hormones, respectively, that naturally occur during these phases of the ovarian cycle.

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Systemic injections of the flavonoid chrysin (5,7-dihydroxyflavone) exert anxiolytic-like effects in ovariectomised and cycling female rats through actions on gamma-aminobutyric acid-A (GABA A ) receptors; however, it is unknown if chrysin directly acts on brain structures that are involved in regulating emotional processes, such as the hippocampus. The present study evaluated the effects of intrahippocampal microinjections of 0.25, 0.5, and 1 µg of chrysin on anxiety-like behaviour in the elevated plus maze (EPM) and locomotor activity test (LAT) in female rats in proestrus and dioestrus. Similar doses of the neurosteroid allopregnanolone were used as a reference GABAergic anxiolytic drug. The participation of the GABA A /benzodiazepine receptor complex was evaluated by administering the antagonists picrotoxin, bicuculline and flumazenil. In proestrus, 0.5 and 1 µg of chrysin and allopregnanolone induced anxiogenic-like behaviour. In dioestrus, chrysin, and allopregnanolone (0.5 µg) induced anxiolytic-like effects. Picrotoxin, bicuculline and flumazenil prevented the effects of chrysin and allopregnanolone in both proestrus and dioestrus. None of the treatments significantly affected locomotor activity. These results indicate that the GABA A /benzodiazepine receptor complex in the dorsal hippocampus regulates the effects of chrysin on anxiety-like behaviour, similar to the actions of allopregnanolone. The divergent effects of treatments across the oestrous cycle phases suggest complex interactions between GABA A receptors and compounds with an anxiolytic potential.

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Background: The prevalence of anxiety and depression in young students is associated with biosocial factors and scholastic stress. However, few studies have evaluated emotional-affective symptoms that are related to the immune system and antioxidant parameters in young individuals without diagnoses of affective disorders. Aim: This study aims to assess the relationship between emotional-affective symptoms and glutathione concentrations and CD4 and CD8 lymphocyte counts in college students. Methods: College students (n = 177) completed standardized psychometric instruments, including the Perceived Stress Scale, Hamilton Anxiety Scale, Beck Depression Inventory, Familiar Social and Friends Support Scale, and Rosenberg Scale. Blood samples were biochemically analyzed. Analyses of variance were conducted between four groups according to symptom severity. Results: A considerable prevalence of stress, anxiety, and depression symptoms was observed and negatively correlated with self-esteem and socio-familiar support. Perceived stress was sexually dimorphic. Although biochemical parameters were within reference ranges, glutathione, CD4, and CD8 tended to be lower in participants with anxiety and depression symptoms, which may be of predictive value. Conclusion: The relationship between antioxidant/immune parameters and socio-affective scores is latent in undiagnosed college students who might develop affective disorders. The findings suggest that during the initial development of affective disorders, stress management strategies should be implemented to help college students cope with the academic load and monitor negative changes in their physiological state.

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Cassava (Manihot esculenta Crantz) is a plant that contains neurotoxins such as linamarin and lotaustraline. Its long-term consumption is associated with neuronal damage and contributes to the development of motor impairment in humans and rats. We investigated the effects of the consumption of cassava juice on renal and hepatic function and motor impairments in male rats. The rats received the vehicle, non-toxic and toxic doses of cassava juice, or linamarin as a pharmacological control, over 35 consecutive days. The effects were evaluated in an open field test, rotarod, and swim test. The toxic cassava dose and linamarin resulted in motor impairments in the rotarod and swim test from day 7 of treatment. The toxic cassava dose and linamarin increased the parameters that indicate renal and hepatic damage, with the exception of total protein and albumin levels. Behavioral variables that show motor incoordination (i.e., latency to fall in the rotarod) were negatively correlated with biochemical parameters of renal and kidney damage, whereas spin behavior was positively correlated. Our data indicate that chronic oral consumption of cassava juice caused renal and hepatic damage that was correlated with motor coordination impairment in rats, similarly to their principal neurotoxic compound, linamarin.

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