Sex and BDNF Val66Met polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice.

Females show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP), the Val66Met polymorphism, within the human BDNF gene, causes impaired activity-dependent secretion of neuronal BDNF and impairments to some forms of memory. We evaluated whether sex and BDNF genotype (Val66Met polymorphism (Met/Met) versus wild-type (Val/Val)) influenced the ability of voluntary running to enhance cognition and hippocampal neurogenesis in mice. Middle-aged C57BL/6J (13 months) mice were randomly assigned to either a control or an aerobic training (AT) group (running disk access). Mice were trained on the visual discrimination and reversal paradigm in a touchscreen-based technology to evaluate cognitive flexibility. BDNF Met/Met mice had fewer correct responses compared to BDNF Val/Val mice on both cognitive tasks. Female BDNF Val/Val mice showed greater cognitive flexibility compared to male mice regardless of AT. Despite running less than BDNF Val/Val mice, AT improved performance in both cognitive tasks in BDNF Met/Met mice. AT increased neurogenesis in the ventral hippocampus of BDNF Val/Val mice of both sexes and increased the proportion of mature type 3 doublecortin-expressing cells in the dorsal hippocampus of female mice only. Our results indicate AT improved cognitive performance in BDNF Met/Met mice and increased hippocampal neurogenesis in BDNF Val/Val mice in middle age. Furthermore, middle-aged female mice may benefit more from AT than males in terms of neuroplasticity, an effect that was influenced by the BDNF Val66Met polymorphism.

Anxiety-like Behavior and GABAAR/BDZ Binding Site Response to Progesterone Withdrawal in a Stress-Vulnerable Strain, the Wistar Kyoto Rats.

Stress susceptibility could play a role in developing premenstrual anxiety due to abnormalities in the hypothalamus-pituitary-adrenal (HPA) axis and impairments in the GABAA receptors' benzodiazepine (BDZ) site. Hence, we studied the stress-vulnerable Wistar Kyoto rat strain (WKY) to evaluate progesterone withdrawal (PW) effects on anxiety, HPA axis response, and to explore indicators of GABAA functionality in the BDZ site. For five days, ovariectomized WKY rats were administered 2.0 mg/kg of progesterone. Twenty-four hours after the last administration, rats were tested in the anxiety-like burying behavior test (BBT) or elevated plus maze test (EPM), and corticosterone was determined. [3H]Flunitrazepam binding autoradiography served as the BDZ binding site index of the GABAA receptor in amygdala nuclei and hippocampus's dentate gyrus (DG). Finally, different doses of diazepam in PW-WKY rats were tested in the BBT. PW induced anxiety-like behaviors in both BBT and EPM compared with No-PW rats. PW increased corticosterone, but was blunted when combined with PW and BBT. PW increased [3H]Flunitrazepam binding in the DG and central amygdala compared with No-PW rats. Diazepam at a low dose induced an anxiogenic-like response in PW rats, suggesting a paradoxical response to benzodiazepines. Overall, PW induced anxiety-like behavior, a blunted HPA axis response, and higher GABAAR/BZD binding site sensitivity in a stress-vulnerable rat strain. These findings demonstrate the role of stress-susceptibility in GABAAR functionality in a preclinical approximation of PMDD.

Effect of physical and sexual violence during childhood and/or adolescence on the development of menstrual related mood disorders: A systematic review and meta-analysis / Efecto de la violencia física y sexual durante la infancia y/o la adolescencia en el desarrollo de trastornos del estado de ánimo relacionados con la menstruación: Una revisión sistemática y metaanálisis

Abstract Background Abuse in early life stages has been proposed as an etiological risk factor for developing menstrually-related mood disorders (MRMDs). Objetive To evaluate whether there is a relation between the occurrence of physical and/or sexual violence in childhood and/or adolescence and the development of MRMDs in adulthood. Method A systematic search was conducted in PubMed, Web of Science, and ScienceDirect, with the route ("Premenstrual Syndrome"[Mesh]) OR ("Premenstrual Dysphoric Disorder"[MeSH]) AND ("Violence"[Mesh]) / ("menstrually-related mood disorders" AND "abuse"). Fifty-four articles were initially reviewed and 32 were excluded based on the criteria. Twenty-two articles were thoroughly reviewed. Finally, five articles (publication years 2014, 2013, 2012, 2007, and 2003) were included in the systematic review and submitted to a meta-analysis. Results Results indicate that having been exposed to physical and/or sexual violence in childhood and/or adolescence increases 1.99 times the risk of experiencing MRMDs in adulthood in comparison with women who did not experience that type of violence (odds ratio [OR] = 1.99; 95% confidence interval [1.58, 2.51]). Discussion and conclusion The present work provides evidence that a woman who experienced violence through physical and/or sexual abuse during childhood and/or adolescence has a greater risk of developing MRMDs in adulthood.

Resumen Antecedentes El abuso en las etapas tempranas de la vida se ha propuesto como un factor de riesgo etiológico para desarrollar trastornos del estado de ánimo relacionados con la menstruación (TEARM). Objetivo Evaluar si existe una relación entre la ocurrencia de violencia física y/o sexual en la infancia y/o la adolescencia y el desarrollo de MRMD en la edad adulta. Método Se realizó una búsqueda sistemática en PubMed, Web of Science y ScienceDirect con la ruta ("Premenstrual Syndrome"[Mesh]) OR ("Premenstrual Dysphoric Disorder"[MeSH]) AND ("Violence"[Mesh]) / ("menstrually-related mood disorders" AND "abuse"). Cincuenta y cuatro artículos fueron revisados inicialmente y 32 fueron excluidos con base en los criterios establecidos. Veintidós artículos fueron revisados exhaustivamente. Por último, se incluyeron cinco artículos (años de publicación 2014, 2013, 2012, 2007 y 2003) en la revisión sistemática, y cinco de ellos fueron sometidos a un metaanálisis. Resultados Los resultados indican que haber estado expuesta a violencia física y/o sexual en la niñez y/o la adolescencia aumenta 1.99 veces el riesgo de experimentar TEARM en la edad adulta en comparación con las mujeres que no experimentaron ese tipo de violencia (odds ratio [OR] = 1.99; intervalo de confianza del 95% [1.58-2.51]). Discusión y conclusión El presente trabajo aporta evidencia de que una mujer que experimentó violencia por abuso físico y/o sexual durante la niñez y/o la adolescencia tiene un mayor riesgo de desarrollar TEARM en la edad adulta.

Risk-based decision making in rats: Modulation by sex and amphetamine.

Decision-making is a complex process essential to daily adaptation in many species. Risk is an inherent aspect of decision-making and it is influenced by gonadal hormones. Testosterone and 17ß-estradiol may modulate decision making and impact the mesocorticolimbic dopamine pathway. Here, we explored sex differences, the effect of gonadal hormones and the dopamine agonist amphetamine on risk-based decision making. Intact or gonadectomised (GDX) male and female rats underwent to a probabilistic discounting task. High and low doses of testosterone propionate (1.0 or 0.2 mg) and 17ß-estradiol benzoate (0.3 µg) were administered to assess acute effects on risk-based decision making. After 3-days of washout period, intact and GDX rats received high or low (0.5 or 0.125 mg/kg) doses of amphetamine and re-tested in the probabilistic discounting task. Under baseline conditions, males made more risky choices during probability discounting compared to female rats, particularly in the lower probability blocks, but GDX did not influence risky choice. The high, but not the low dose, of testosterone modestly reduced risky decision making in GDX male rats. Conversely, 17ß-estradiol had no significant effect on risky choice regardless of GDX status in either sex. Lastly, a higher dose of amphetamine increased risky decision making in both intact males and females, but had no effect in GDX rats. These findings demonstrated sex differences in risk-based decision making, with males showing a stronger bias toward larger, uncertain rewards. GDX status influenced the effects of amphetamine, suggesting different dopaminergic regulation in risk-based choices among males and females.

Evaluation of hormonal and metabolic factors related to depression in reproductive age women / Evaluación de factores hormonales y metabólicos relacionados con la depresión en mujeres en edad fértil

Abstract Introduction Major depressive disorder (MDD) is a prevalent disease affecting women more than men worldwide. Various factors are involved in the genesis of depression, including hormones such as testosterone and certain metabolic factors Objective To evaluate hormone levels and metabolic variables in women with major depression and healthy controls. Method A cross-sectional, comparative analytical study was conducted in 40 participants, 23 patients with an MDD diagnosis and 17 controls, all of women in reproductive age between the ages of 18 and 45. Sociodemographic variables, hormonal profile, and metabolic variables were assessed and the 17-item Hamilton Depression Scale was used to evaluate depressive symptoms. Results No statistically significant differences were observed between the groups in the hormonal and metabolic variables explored. Nevertheless, it was observed that the lower the testosterone levels and the higher the serum glucose levels, the more intense depressive symptoms were. Discussion and conclusion Testosterone is associated with a lower depressive symptoms score on the Hamilton Depression scale, suggesting a potential antidepressant effect, whereas high glucose levels are associated with a higher score on this scale. We believe that the measurement of hormonal and metabolic variables in women can contribute to a better understanding of the pathophysiology of depression.

Resumen Introducción El trastorno depresivo mayor (TDM) es una enfermedad prevalente a nivel mundial, que afecta más a mujeres que a hombres. En la génesis de la depresión se consideran diversos factores, entre ellos algunas hormonas como la testosterona y ciertos factores metabólicos Objetivo Evaluar los niveles de hormonas y variables metabólicas en mujeres con depresión mayor y controles sanas. Método Se realizó un estudio transversal, comparativo y analítico en 40 participantes, 23 pacientes con diagnóstico de TDM y 17 controles, todas ellas mujeres de 18 a 45 años en periodo reproductivo. Se evaluaron variables sociodemográficas, perfil hormonal y variables metabólicas, y se aplicó la Escala de Depresión de Hamilton de 17 reactivos para evaluar los síntomas depresivos. Resultados No se observaron diferencias estadísticamente significativas entre los grupos en las variables hormonales y metabólicas exploradas. Sin embargo, se observó que, cuanto menores eran los niveles de testosterona y mayores los de glucosa sérica, los síntomas depresivos eran de mayor intensidad. Discusión y conclusión La testosterona se asocia con un menor puntaje de síntomas depresivos en la Escala Hamilton, lo que sugiriere un potencial efecto antidepresivo, mientras que los niveles altos de glucosa se asocian con un mayor puntaje en dicha escala. Consideramos que la medición de variables hormonales y metabólicas en la mujer puede contribuir a mejorar el conocimiento de la fisiopatología de la depresión.

Anxiolytic- and anxiogenic-like effects of Montanoa tomentosa (Asteraceae): Dependence on the endocrine condition.

ETHNOPHARMACOLOGICAL RELEVANCE: Montanoa tomentosa Cerv. (MT) is a native plant from Mexico used in traditional medicine as a remedy for reproductive impairments and relaxing effects. In previous studies, it has been shown that the endocrine state could modify the antianxiety-like actions of anxiolytic compounds. Although women are the primary user of MT, no studies have evaluated the potential impact of the endocrine milieu on its anti-anxiety actions. AIMS OF THE STUDY: Ascertain the antianxiety effects of M. tomentosa in rats with different hormonal conditions, and to analyze the participation of the GABAA receptor in ovariectomized rats treated with MT. MATERIALS AND METHODS: The animal model of anxiety used was the elevated plus-maze (EPM). Rats' endocrine conditions were: a) Low hormone levels (rats in diestrus I and II phases); b) High hormone levels (proestrus/estrus phases); c) No hormones (ovariectomized rats); and d) Rats under progesterone withdrawal (PW). To evaluate the participation of the GABAA receptor in the anxiolytic-like action of MT the antagonist picrotoxin was used. RESULTS: Results showed that MT induced dose-dependent anxiolytic-like actions in rats with low hormone level conditions. Also, MT reduced anxiety-like behavior in female rats under PW, in contrast to diazepam which was ineffective. MT's anxiolytic-like effect was blocked by picrotoxin, suggesting the participation of the GABAA receptor complex. However, increased anxiety-like behavior was observed in rats with a high hormone level condition and low doses of MT. CONCLUSIONS: Beneficial anxiolytic-like actions of MT are observed under low hormone conditions, particularly in the PW challenge (a condition that can be related to a premenstrual period). Furthermore, the participation of the GABAA receptor is evidenced. However, hormonal variations could induce the opposite effects, hence women should be cautious.