Anxiety in Natural and Surgical Menopause — Physiologic and Therapeutic Bases

Generalized anxiety disorder is one of the most common psychiatric disorders, affecting a high percentage of human beings around the world. This emotional disorder possesses marked gender differences and occurs more often in women than in men, in a proportion of 2:1. Accompanying the reproductive cycle of women are significant fluctuations in plasma and brain steroid hormone concentrations, including oestradiol, progesterone, and allopregnanolone, among others. These hormonal changes are related to some illnesses and with the development of anxiety and mood swings occurring in the premenstrual and postpartum period, and particularly during the menopause. Menopause is a clinical term used to indicate the cessation of the woman\u27s reproductive ability that occurs naturally, but also may be surgically induced by bilateral oophorectomy, with or without the removal of the Fallopian tubes and uterus. Natural menopause includes specific periods related to the physiological and hormonal changes produced by ovarian failure, it is usually a natural stage that occurs to women in midlife, during their late 40s or early 50s, indicating the end of the reproductive period in the woman. During the menopause transition years, women experience changes in the production of ovarian hormones, which are associated with significant changes in the physiological, emotional, and affective processes. Unfortunately, surgical menopause occurs at an early age, and produces similar physiological and psychiatric disorders, but they are more severe in this instance. In both cases, typical symptoms associated with menopause critically deteriorate the mental health of the women. In this way, the therapeutic management of clinical symptoms of menopause include replacement hormone therapy, the use of anxiolytic and antidepressant drugs, and other natural alternatives based on the use of chemical compounds obtained from plants such as soya. However, a general effective treatment for menopause symptoms does not yet exist. For this reason, experimental studies have proposed ovariectomy in rats as a potential tool to study the effects of a long-term absence of ovarian hormones associated with surgical menopause, which also allowed the study of substances with potential therapeutic application to ameliorate typical symptoms associated with surgical menopause. The aim of this chapter is to review the participation of ovarian hormones in the regulation of emotional and affective disorders in women with natural or surgical menopause; particularly their anatomical pathways, neurotransmission systems, and the resulting behavioural patterns. Finally, preclinical and clinical research suggested that long-term absence of ovarian hormones associated with natural or surgical menopause is the principal cause of physiological and psychiatric disorder in the women; therefore, oestrogenic compounds seem to play an important role in the maintenance of the brain structures that regulate anxiety, mood, memory, and cognitive functions in menopausal women

Differential effects of acute and chronic treatment with the flavonoid chrysin on anxiety-like behavior and Fos immunoreactivity in the lateral septal nucleus in rats

The aim of this study was to compare the effects of acute (a single injection) and chronic (21 consecutive days) treatments with chrysin 2, 4, and 8 umol kg–1 on anxiety-like behavior and Fos immunoreactivity in the lateral septum nucleus (LSN), a structure that is involved in the regulation of anxiety, in male Wistar rats. These effects were compared with the clinically effective anxiolytic diazepam 7 umol kg–1. The results showed that acute, but not chronic treatment, with 4 umol kg-1 chrysin exerted anxiolytic- and antidepressant-like effects, andwith these effects were being similar to that of diazepam. Also, none of the above above-mentioned treatments did alter Fos immunoreactivity in the LSN, but a tendency towards athe reduction of this variable was detected with chrysin 4 umol kg–1 and diazepam 7 umol kg–1. Altogether, results suggest that chrysin exerts anxiolytic-like effects, but however, it can produce pharmacological tolerance after repeated use, similar to benzodiazepines

Neuropharmacology of Anxiety Disorders at Young Age: A Perspective from Preclinical Research

Anxiety is one of the most common psychopathologies in the general population that often begin early in life; however, research on this disorder during early developmental stages has been poorly explored compared to adults. A better understanding of the anxiety disorder through childhood is essential to develop more effective treatments. This chapter provides a general overview of the usefulness of animal models of childhood anxiety and its neurobiological bases to discuss how the studies on animals meet the several criteria of validity to discover pathophysiological mechanisms of human disorders and new treatments for these conditions. The research methodology for this chapter consisted in using a thesaurus system such as Medical Subject Headings (MeSH) terms of the National Library of Medicine to find original articles in databases as PubMed or Web of Science about preclinical findings related to the neuropharmacology of anxiety before adulthood. The contribution of this chapter is to provide data from preclinical studies which are encouraged to a better comprehension of anxiety at young age

Menopause in Nonhuman Primates: A Comparative Study with Humans

Although menopause is a phenomenon predominantly studied in humans or laboratory animals, this chapter discussed the case of nonhuman primates (NHPs), not only with the objective of employing them as study models but also to better understand phylogenetic divergence among species. Those taxonomic differences are reflected in reproductive processes that may be similar to those of human beings, with the presence of a defined cycle or periods of estrus, but perhaps at different ages as well, where menopause plays a crucial role. First, it is important to delimit the concept of menopause by considering its anatomical, physiological, and biochemical parameters, including the cessation of menstrual bleeding or perineal swelling—when present—or follicular depletion and hormonal changes. Thus, the aim of this chapter is to discuss some of the similarities between NHPs and human females, during the menopause period. Studying these phenomena should help us achieve a better understanding of the social, physiological, and environmental factors without adopting any particular cultural view of menopause

Berry Supplementation and Their Beneficial Effects on Some Central Nervous System Disorders

This chapter is based in the compilation and analysis of different in vitro, preclinical, and clinical studies, which explored the potential beneficial bioactivity of supplementation with berries on some alterations in the central nervous system (CNS). The last section of the chapter describes the possible mechanisms of action of polyphenols, anthocyanins, and other compounds present in berries as well as their relationship with anxiety, depression, and Alzheimer’s (AD) and Parkinson’s diseases (PD) and their implication in the prevention of cognitive decline and senescence motor functions. Electronic databases as Springer, PubMed, Scopus, and Elsevier were used. Papers were selected by topic specially those related with berries, year of publication, and authors. The present chapter evidenced the potential health effect as neuroprotector of different berries and their bioactive compounds mainly flavonoids, polyphenols, and anthocyanins, on diseases such as anxiety, depression, and Alzheimer’s and Parkinson’s diseases. In conclusion, for human nutrition berry fruit supplementation might be an excellent source of antioxidant and alternative for prevention and reduction of symptoms in diseases such as anxiety, depression, Alzheimer’s, and Parkinson’s

The Causative and Curative Roles of Brain-Derived Neurotrophic Factor in Parkinson’s Disease

Parkinson’s disease (PD) is characterized by the activation of degenerative and inflammatory processes in brain circuits that control movement and, according to the degree of progression of the damage, can cause neuropsychological disorders such as cognitive dysfunction. Changes in gene expression profile or post-translational modifications in secretory proteins such as neurotrophic factors could define the disease progression. Brain-derived neurotrophic factor (BDNF) is relevant, because it not only participates in neuronal survival, neurotransmission, dendritic growth and cellular communication but also in disease progression. In this chapter, considering both experimental evidences and clinical reports, the authors will analyze the contribution of BDNF as one of the causes of neurodegeneration and neuroinflammation; discuss the participation of this neurotrophic factor in the development of cognitive dysfunction, and finally the scope of novel BDNF-based therapies for PD

Efecto de la ovariectomía a lo largo del tiempo sobre la ansiedad y la expresión de la proteína Fos en el Núcleo Septal Lateral de la rata Wistar

La menopausia natural subyace al decline de la función ovárica que se refleja en la disminución de las concentraciones plasmáticas y cerebrales de hormonas como estradiol y progesterona, entre otras sustancias. Sin embargo, algunas mujeres a edad temprana experimentan la “menopausia quirúrgica” debido a condiciones médicas que requieren la extirpación de los ovarios (con o sin la matriz), en cuyos casos las alteraciones emocionales como la ansiedad y la depresión son más severas que las que ocurren durante la menopausia natural. En la investigación preclínica se ha utilizado a la rata ovariectomizada para estudiar los cambios fisiológicos y emocionales que se presentan durante la menopausia quirúrgica. No obstante, se carece de estudios que hayan caracterizado los efectos de la ovariectomía a lo largo del tiempo sobre los cambios emocionales y motivacionales, así como su relación con los cambios neurofisiológicos en neuronas de estructuras cerebrales involucradas con la regulación del estado emocional, como es el caso del Núcleo Septal Lateral. Objetivo. Caracterizar los efectos de la ovariectomía (1,3,6,9,12 y 15 semanas post ovariectomía) sobre la ansiedad, la respuesta conductural ante el estrés agudo y la expresión de la proteína Fos en el Núcleo Septal Lateral de la rata Wistar

Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases

Plant-derived compounds have recently attracted greater interest in the field of new therapeutic agent development. These compounds have been widely screened for their pharmacological effects. Polyphenols, such as soy-derived isoflavones, also called phytoestrogens, have been extensively studied due to their ability to inhibit carcinogenesis. These compounds are chemically similar to 17β-estradiol, and mimic the binding of estrogens to its receptors, exerting estrogenic effects in target organs. Genistein is an isoflavone derived from soy-rich products and accounts for about 60% of total isoflavones found in soybeans. Genistein has been reported to exhibit several biological effects, such as anti-tumor activity (inhibition of cell proliferation, regulation of the cell cycle, induction of apoptosis), improvement of glucose metabolism, impairment of angiogenesis in both hormone-related and hormone-unrelated cancer cells, reduction of peri-menopausal and postmenopausal hot flashes, and modulation of antioxidant effects. Additionally, epidemiological and clinical studies have reported health benefits of genistein in many chronic diseases, such as cardiovascular disease, diabetes, and osteoporosis, and aid in the amelioration of typical menopausal symptoms, such as anxiety and depression. Although the biological effects are promising, certain limitations, such as low bioavailability, biological estrogenic activity, and effects on target organs, have limited the clinical applications of genistein to some extent. Moreover, studies report that modification of its molecular structure may eliminate the biological estrogenic activity and its effects on target organs. In this review, we summarize the potential benefits of genistein on menopause symptoms and menopause-related diseases like cardiovascular, osteoporosis, obesity, diabetes, anxiety, depression, and breast cancer

Pharmacological, Neurochemical, and Behavioral Mechanisms Underlying the Anxiolytic- and Antidepressant-like Effects of Flavonoid Chrysin

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