The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex-and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress.Key words: oestrogens, progestogens, androgens, neurogenesis, hippocampus, depression, reproductive experience, cognition doi: 10.1111/jne.12070Adolescence, pregnancy, postpartum and menopause are associated with dramatic changes in steroid hormone levels (1-3) and, in turn, a greater prevalence of neuropsychiatric disorders (4-6). For the past two decades, we have been researching how steroid hormones affect both brain and behaviour, with an emphasis on hippocampal plasticity, cognition and depression. Sex differences are prevalent in steroid hormone-induced modulation of hippocampus-dependent neuroplasticity and cognition. These findings may be related to the sex-related differences in the incidence and symptoms of neuropsychiatric and neurodegenerative disorders. For example, women are more likely to be diagnosed with depression (6) or Alzheimer's disease (4,7), whereas men or boys are more likely to be diagnosed with Parkinson's disease or autism (8,9). It is important to consider that females have a unique physiology allowing for gestation, parturition and lactation. This unique physiology may render females more vulnerable or resilient to certain neurological disorders. Indeed, pregnancy and motherhood are associated with a host of changes to brain, behaviour and the endocrine profile (10) and so it is not unexpected that there may be permanent changes in the female brain's response to hormones. We have focussed on changes in the hippocampus, as a result of the involvement of this region in brain disorders modulated by sex and sex...
Sex differences in neurological disease exist in incidence, severity, progression, and symptoms and may ultimately influence treatment. Cognitive disturbances are frequent in neuropsychiatric disease with men showing greater cognitive impairment in schizophrenia, but women showing more severe dementia and cognitive decline with Alzheimer's disease. Although there are no overall differences in intelligence between the sexes, men, and women demonstrate slight but consistent differences in a number of cognitive domains. These include a male advantage, on average, in some types of spatial abilities and a female advantage on some measures of verbal fluency and memory. Sex differences in traits or behaviors generally indicate the involvement of sex hormones, such as androgens and estrogens. We review the literature on whether adult levels of testosterone and estradiol influence spatial ability in both males and females from rodent models to humans. We also include information on estrogens and their ability to modulate verbal memory in men and women. Estrone and progestins are common components of hormone therapies, and we also review the existing literature concerning their effects on cognition. We also review the sex differences in the hippocampus and prefrontal cortex as they relate to cognitive performance in both rodents and humans. There has been greater recognition in the scientific literature that it is important to study both sexes and also to analyze study findings with sex as a variable. Only by examining these sex differences can we progress to finding treatments that will improve the cognitive health of both men and women. © 2016 American Physiological Society. Compr Physiol 6:1295-1337, 2016.
Menopause is associated with cognitive decline, and hormone therapies (HTs) may improve cognition depending on type and timing of HTs. Previous parity may influence cognition in later life. We investigated how primiparity and long-term ovariectomy influence cognition, neurogenesis, hormones, cytokines, and neuronal activation in middle-aged rats in response to Premarin, an HT. Nulliparous and primiparous rats were sham-ovariectomized or ovariectomized, administered vehicle or Premarin 6 months later, and all rats were trained in the Morris water maze. Premarin improved early spatial learning and memory in nulliparous rats but impaired early learning in primiparous rats. With training, primiparity increased hippocampal neurogenesis, and Premarin decreased immature neurons, regardless of parity. Moreover, Premarin increased serum tumor necrosis factor α and the CXC chemokine ligand 1 (CXCL1) in trained nulliparous, but not primiparous, rats. However, Premarin decreased the expression of the immediate early gene zif268 in the dorsal CA3 region in primiparous rats after training. Thus, primiparity alters how Premarin affects spatial learning, neuronal activation, and serum cytokines. These findings have implications for the treatment of age-associated cognitive decline in women.
Introduction: According to the interpersonal model of depression, individuals with depression engage in excessive reassurance-seeking (ERS) about others’ beliefs regarding their self-worth, which can ultimately result in interpersonal rejection. We present the novel hypothesis that maladaptive ERS behaviors in depression may be driven by difficulties with “theory of mind”—the foundational ability to decode and reason about others’ mental states. Method: Participants included 31 young adults in a current episode of a unipolar depressive disorder, and 91 never-depressed adults. Theory of mind was assessed with standard, objective laboratory tasks. Stressful life events were assessed with a gold-standard contextual interview and independent rating system. Results: Consistent with hypotheses, in the depressed group only, lower accuracy of theory of mind decoding was associated with greater ERS, which was significantly associated with exposure to greater interpersonal, but not non-interpersonal, stress. Surprisingly, higher accuracy of theory of mind reasoning was associated with greater ERS. Discussion: The intriguing dissociation is discussed in terms of expanding the interpersonal model of depression to include the foundational social cognitive processes that underlie effective social communication.
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