Evaluating different models of maternal stress on stress-responsive systems in prepubertal mice.

Introduction: Maternal adversity during pregnancy influences neurodevelopment in human and model animal offspring. Adversity can result from stressors coming from many different directions ranging from environmental to nutritional and physiological to immune (e.g.

Glucocorticoid regulation of diurnal spine plasticity in the murine ventromedial prefrontal cortex.

The ventromedial prefrontal cortex (vmPFC) regulates fear acquisition, fear extinction, mood, and HPA axis function. Multiple brain regions exhibit time-of-day dependent variations in learning, long term potentiation (LTP), and dendritic morphology. Glucocorticoids have been implicated in the regulation of dendritic structure in the context of stress.

Sex differences in autonomic responses to stress: implications for cardiometabolic physiology.

Chronic stress is a significant risk factor for negative health outcomes. Furthermore, imbalance of autonomic nervous system control leads to dysregulation of physiological responses to stress and contributes to the pathogenesis of cardiometabolic and psychiatric disorders. However, research on autonomic stress responses has historically focused on males, despite evidence that females are disproportionality affected by stress-related disorders.

The Effects of Chronic Variable Stress and Photoperiod Alteration on the Hypothalamic-Pituitary-Adrenal Axis Response and Behavior of Mice.

The hypothalamic-pituitary-adrenal (HPA) axis mediates the physiological response to stressors and also synchronizes different physiological systems to environmental cues. Changes in day length (i.e.

Sex Differences in Acute Neuroendocrine Responses to Stressors in Rodents and Humans.

Sex differences in the neuroendocrine response to acute stress occur in both animals and humans. In rodents, stressors such as restraint and novelty induce a greater activation of the hypothalamic-pituitary-adrenal axis (HPA) in females compared to males. The nature of this difference arises from steroid actions during development (organizational effects) and adulthood (activational effects).

Androgens and Their Role in Regulating Sex Differences in the Hypothalamic/Pituitary/Adrenal Axis Stress Response and Stress-Related Behaviors.

Androgens play a pivotal role during development. These gonadal hormones and their receptors exert organizational actions that shape brain morphology in regions controlling the stress regulatory systems in a male-specific manner. Specifically, androgens drive sex differences in the hypothalamic/pituitary/adrenal (HPA) axis and corresponding hypothalamic neuropeptides.

Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.

Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.

Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.

Sex Differences in Hemoglobin A1c Levels Related to the Comorbidity of Obesity and Depression.

Obesity (OB) and major depressive disorder (MDD) are chronic conditions associated with disease burden, and their comorbidity appears more common among women. Mechanisms linking these conditions may involve inflammatory and metabolic pathways. The goal of this study was to evaluate the impact of MDD on relationships between OB and cardiometabolic function, and sex differences therein.

Gut microbiota and metabolic marker alteration following dietary isoflavone-photoperiod interaction.

Introduction: The interaction between isoflavones and the gut microbiota has been highlighted as a potential regulator of obesity and diabetes. In this study, we examined the interaction between isoflavones and a shortened activity photoperiod on the gut microbiome.

Methods: Male mice were exposed to a diet containing no isoflavones (NIF) or a regular diet (RD) containing the usual isoflavones level found in a standard vivarium chow.

The Hypothalamic-Pituitary-Adrenal Axis: Development, Programming Actions of Hormones, and Maternal-Fetal Interactions.

The hypothalamic-pituitary-adrenal axis is a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis. Abnormal development of the hypothalamic-pituitary-adrenal (HPA) axis can further result in long-term alterations in neuropeptide and neurotransmitter synthesis in the central nervous system, as well as glucocorticoid hormone synthesis in the periphery. Together, these changes can potentially lead to a disruption in neuroendocrine, behavioral, autonomic, and metabolic functions in adulthood.

Knockout of the circadian gene, Per2, disrupts corticosterone secretion and results in depressive-like behaviors and deficits in startle responses.

Background: The Period Circadian Regulator 2 (Per2) gene is important for the modulation of circadian rhythms that influence biological processes. Circadian control of the hypothalamus-pituitary-adrenal (HPA) axis is critical for regulation of hormones involved in the stress response. Dysregulation of the HPA axis is associated with neuropsychiatric disorders.

Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses.

Estradiol and testosterone are powerful steroid hormones that impact brain function in numerous ways. During development, these hormones can act to program the adult brain in a male or female direction. During adulthood, gonadal steroid hormones can activate or inhibit brain regions to modulate adult functions.

Social isolation alters hypothalamic pituitary adrenal axis activity after chronic variable stress in male C57BL/6 mice.

The chronic variable stress (CVS) paradigm is frequently used to model the changes in hypothalamic pituitary adrenal (HPA) axis function characteristic of many stress-related diseases. However, male C57BL/6 mice are typically resistant to CVS's effects, making it difficult to determine how chronic stress exposure may alter acute HPA function and regulation in these mice. As social support in rodents can profoundly influence physiological and behavioral processes, including the HPA axis, we sought to characterize the effects of CVS exposure on basal and acute stress-induced HPA axis function in pair- and single-housed adult male mice.

Sex-Dependent Mechanisms of Glucocorticoid Regulation of the Mouse Hypothalamic Corticotropin-Releasing Hormone Gene.

To limit excessive glucocorticoid secretion following hypothalamic-pituitary-adrenal (HPA) axis stimulation, circulating glucocorticoids inhibit corticotropin-releasing hormone (CRH) expression in paraventricular nucleus (PVN) neurons. As HPA function differs between sexes and depends on circulating estradiol (E2) levels in females, we investigated sex/estrous stage-dependent glucocorticoid regulation of PVN Crh. Using NanoString nCounter technology, we first demonstrated that adrenalectomized (ADX'd) diestrous female (low E2), but not male or proestrous female (high E2), mice exhibited a robust decrease in PVN CRH mRNA following 2-day treatment with the glucocorticoid receptor (GR) agonist RU28362.

Chronic variable stress alters hypothalamic-pituitary-adrenal axis function in the female mouse.

Chronic stress is often associated with a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which can greatly increase risk for a number of stress-related diseases, including neuropsychiatric disorders. Despite a striking sex-bias in the prevalence of many of these disorders, few preclinical studies have examined female subjects. Hence, the present study aimed to explore the effects of chronic stress on the basal and acute stress-induced activity of the HPA axis in the female C57BL/6 mouse.

Androgens Drive Sex Biases in Hypothalamic Corticotropin-Releasing Hormone Gene Expression After Adrenalectomy of Mice.

Although prominent sex differences exist in the hypothalamic-pituitary-adrenal axis's response to stressors, few studies of its regulation in the hypothalamic paraventricular nucleus (PVN) have compared both male and female subjects. In this study, we sought to explore sex differences in the acute regulation of PVN neuropeptide expression following glucocorticoid (GC) removal and the underlying role of gonadal hormones. We first examined the effects of short-term adrenalectomy (ADX) on PVN Crh and arginine vasopressin (Avp) expression in mice using in situ hybridization.

Isoflavones Alter Hypothalamic-Pituitary-Adrenal Axis Response Following Photoperiod Alteration.

Photoperiod and diet are factors known to modulate the hypothalamic-pituitary-adrenal (HPA) axis. Specifically, shifts in photoperiod have been previously linked with affective and anxiety disorders. Furthermore, isoflavones have been shown to mediate behavioral outcome in response to the environment of the animal.

Sex related biases for attending to object color versus object position are reflected in reaction time and accuracy.

Processing of visual features related to objects and space relations occurs within separate cortical streams that interact with selective attention. Such separation has implications for cognitive development because the perception of 'what' and 'where' provide a neural foundation for the development of aspects of higher cognition. Thus, a small attentional bias in early development for attending to one aspect over the other might influence subsequent higher cognitive processing in tasks involving object recognition and space relations.

Sex-Dependent Effects of Mild Blast-induced Traumatic Brain Injury on Corticotropin-releasing Factor Receptor Gene Expression: Potential Link to Anxiety-like Behaviors.

Traumatic brain injury (TBI) affects 1.7 million people in the United States every year, resulting in increased risk of death and disabilities. A significant portion of TBIs experienced by military personnel are induced by explosive blast devices.

Sex Differences in the Prenatal Programming of Adult Metabolic Syndrome by Maternal Androgens.

Context: Growing preclinical evidence suggests that hormonal programming by androgens in utero may contribute to cardiovascular disease risk in adult offspring. However, the effect of prenatal androgens on cardiometabolic outcomes in the human population, especially their potential differential impact on male vs female offspring, has not been well studied.

Design: Adult offspring (n = 274) of mothers enrolled in the New England birth cohorts of the Collaborative Perinatal Project were assessed at ages 39 to 50.

Sex differences in the hypothalamic-pituitary-adrenal axis' response to stress: an important role for gonadal hormones.

The hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine network that controls hormonal responses to internal and external challenges in an organism's environment, exhibits strikingly sex-biased activity. In adult female rodents, acute HPA function following a stressor is markedly greater than it is in males, and this difference has largely been attributed to modulation by the gonadal hormones testosterone and estradiol. These gonadal hormones are produced by the hypothalamic-pituitary-gonadal (HPG) axis and have been shown to determine sex differences in adult HPA function after acute stress via their activational and organizational effects.

Characterization of Activation of the Hypothalamic-Pituitary-Adrenal Axis by the Herbicide Atrazine in the Female Rat.

Atrazine (ATR) is a commonly used pre-emergence and early postemergence herbicide. Rats gavaged with ATR and its chlorometabolites desethylatrazine (DEA) and deisopropylatrazine (DIA) respond with a rapid and dose-dependent rise in plasma corticosterone, whereas the major chlorometabolite, diaminochlorotriazine (DACT), has little or no effect on corticosterone levels. In this study, we investigated the possible sites of ATR activation of the hypothalamic-pituitary-adrenal (HPA) axis.

Sex differences in major depression and comorbidity of cardiometabolic disorders: impact of prenatal stress and immune exposures.

Major depressive disorder topped ischemic heart disease as the number one cause of disability worldwide in 2012, and women have twice the risk of men. Further, the comorbidity of depression and cardiometabolic disorders will be one of the primary causes of disability worldwide by 2020, with women at twice the risk. Thus, understanding the sex-dependent comorbidities has public health consequences worldwide.

Chronic Variable Stress Induces Sex-Specific Alterations in Social Behavior and Neuropeptide Expression in the Mouse.

Chronic exposure to stressors impairs the function of multiple organ systems and has been implicated in increased disease risk. In the rodent, the chronic variable stress (CVS) paradigm has successfully modeled several stress-related illnesses. Despite striking disparities between men and women in the prevalence and etiology of disorders associated with chronic stress, most preclinical research examining chronic stressor exposure has focused on male subjects.

Differential Responses of the HPA Axis to Mild Blast Traumatic Brain Injury in Male and Female Mice.

Traumatic brain injury (TBI) affects 10 million people worldwide, annually. TBI is linked to increased risk of psychiatric disorders. TBI, induced by explosive devices, has a unique phenotype.