Background Multiple sclerosis (MS) is characterized by two neuropathological key aspects: inflammation and neurodegeneration. Clinical studies support a prospective link between psychological stress and subsequent inflammatory disease activity. However, it is unknown if a similar link exists for grey matter (GM) degeneration as the key driver of irreversible disability. Methods We tested whether neural

Studies demonstrate a role for the bed nucleus of the stria terminalis (BNST) in modulating affective behavior and stress-reward integration. To explore the dynamic nature of in vivo BNST activity associated with anxiety-like behavior in a stress-inducing context, we utilized fiber photometry and detected BNST calcium transients in mice during the novelty-suppressed feeding task (NSFT). Phasic BNST

Sex and exposure to chronic stress have been identified as risk factors for developing Alzheimer's disease (AD). Although AD has been demonstrated to be more prevalent in females, sex is often overlooked in research studies, likely due to the complexity of the hormonal status. In female rats, the reproductive status can modulate the well-known increase in tau phosphorylation (pTau) caused by the exposure

Since its development in 1993, the Trier Social Stress Test (TSST) has been used widely as a psychosocial stress paradigm to activate the sympathetic nervous system and hypothalamic-pituitary-adrenal axis (HPAA) stress systems, stimulating physiological functions (e.g. heart rate) and cortisol secretion. Several methodological variations introduced over the years have led the scientific community to

Several studies have demonstrated poor retention of extinction learning among individuals with posttraumatic stress disorder (PTSD). Gonadal hormone signaling in brain appears to influence the retention of extinction learning differently in women with and without PTSD. Women with PTSD, compared to trauma-exposed women without PTSD, show relative deficits in extinction retention during the mid-luteal

Humans inevitably go through various stressful events, which initiates a chain of neuroendocrine reactions that may affect brain functions and lead to psychopathological symptoms. Previous studies have shown stress-induced changes in activation of individual brain regions or pairwise inter-regional connectivity. However, it remains unclear how large-scale brain network is reconfigured in response to

Cocaine use and withdrawal prompt stress system responses. Stress and the negative affective state produced by cocaine withdrawal are major triggers for relapse. FKBP5 is a co-chaperone of the glucocorticoid receptor and regulates HPA axis negative feedback. The role of FKBP5 in cocaine-related behaviors has not been studied. The FKBP5 inhibitor SAFit2 was used to examine the role of FKBP5 in anxiety-like

The ability of an individual to reduce the intensity, duration or frequency of a stressor is a critical determinant of the consequences of that stressor on physiology and behavior. To expand our understanding of the brain networks engaged during controllable and uncontrollable stress and to identify sex differences, we used functional connectivity analyses of the immediate early gene product Fos in

The ability to cope with stress is essential for emotional stability and mental health. It is also hypothesized that factors promoting resilience to stress may offer treatment strategies for maladaptive disorders such as anxiety and depression. Here, we find that physical restraint reduces the expression of type 1 adenylyl cyclase (Adcy1), a neurospecific synaptic enzyme that positively regulates the

Chronic stress represents a vulnerability factor for anxiety and depressive disorders and has been widely used to model aspects of these disorders in rodents. Disinhibition of somatostatin (SST)-positive GABAergic interneurons in mice by deletion of γ2 GABAA receptors selectively from these cells (SSTCre:γ2f/f mice) has been shown to result in behavioral and biochemical changes that mimic the responses

Early life stress paradigms have become prominent in the animal literature to model atypical development. Currently, two models have prevailed within the literature: (1) limited bedding or nesting and (2) maternal separation or deprivation. Both models have produced aberrations spanning behavior and neural circuitry. Surprisingly, these two models have yet to be directly compared. The current study

Gulf War illness is associated with a combination of exposure to war-related chemical agents and traumatic stress. Currently, there are no effective treatments, and the pathophysiology remains elusive. Neurological problems are among the most commonly reported symptoms. In this study, we investigated the glutamatergic system in the hippocampi of mice exposed to war-related chemical agents and stress

Post-traumatic stress disorder (PTSD) is a mental health condition that is triggered by a stressful event, with symptoms including exaggerated startle response, intrusive traumatic memories and nightmares. The single prolonged stress (SPS) is a multimodal stress protocol that comprises a sequential exposure to physical restraint, forced swimming, predator scent and ether anesthesia. This procedure

Losing an only child is a devastating life event that a parent can experience and may lead to post-traumatic stress disorder (PTSD). Social support could buffer against the negative influence of this trauma, but the neural mechanism underlying this alleviation effect remains poorly understood. In this study, voxel-based morphometry was conducted on brain MRI of 220 Han Chinese adults who had lost their

Allopregnanolone, a GABAergic neurosteroid and progesterone derivative, was recently approved by the Food and Drug Administration for the treatment of postpartum depression (PPD). Several mechanisms appear to be involved in the pathogenesis of PPD, including neuroendocrine dysfunction, neuroinflammation, neurotransmitter alterations, genetic and epigenetic modifications. Recent evidence highlights

A new school of thought in evolutionary developmental biology, combined with research in the neurobiology of stress, suggest that early exposure to stressful circumstances may be a cause of dyslexia. A balance between epigenetic, stress-induced and cognitive-growth genetic programs modulates the brain's cellular, regional, and network homeostasis. This balance is essential for adaptability to the normative

Given that multiple neurobiological systems, as well as components within these systems are impacted by stress, and may interact in additive, compensatory and synergistic ways to promote or mitigate PTSD risk, severity, and recovery, we thought that it would be important to consider the collective, as well as separate effects of these neurobiological systems on PTSD risk. With this goal in mind, we

Psychosocial stress is the major form of stress faced by children and adolescents and is an important risk factor for the development of mental illnesses. Chronic social defeat stress (CSDS) is a preclinical mouse model that induces an entire spectrum of phenotypes with similar interindividual variability as seen in humans. Following CSDS, adult male mice have been characterized as being either susceptible

Allopregnanolone (3α,5α-tetrahydroprogesterone; pharmaceutical formulation: brexanolone) is a neurosteroid that has recently been approved for the treatment of postpartum depression, promising to fill part of a long-lasting gap in the effectiveness of pharmacotherapies for depressive disorders. In this review, we explore the experimental research that characterized the antidepressant-like effects of

Avoidance behavior is a hallmark in pathological anxiety disorders and results in impairment of daily activities. Individual differences in avoidance responses are critical in determining vulnerability or resistance to anxiety disorders. Dopaminergic activation is implicated in the processing of avoidance responses; however, the mechanisms underlying these responses are unknown. In this sense, we used

Understanding neural mechanisms that confer risk for posttraumatic stress disorder (PTSD) is critical for earlier intervention, yet longitudinal work has been sparse. The amygdala is part of a core network consistently implicated in PTSD symptomology. Most neural models of PTSD have focused on the amygdala's interactions with the dorsal anterior cingulate cortex, ventromedial prefrontal cortex, and

Allopregnanolone is synthesized in the central nervous system either de novo from cholesterol or from steroid hormone precursors like progesterone and pregnenolone. Over the past 30 years, direct and rapid, non-genomic actions of allopregnanolone and its derivatives via GABAA receptors have been demonstrated. Changes in brain levels of allopregnanolone during pregnancy and in the postpartum period

Premenstrual dysphoric disorder (PMDD) is a severe mood disorder with core symptoms (affective lability, irritability, depressed mood, anxiety) and increased sensitivity to stress occurring in the luteal phase of the menstrual cycle. PMDD can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones (NASs). In this review, we describe the role of the NAS allopregnanolone

Postpartum depression (PPD) is a unique subtype of major depressive disorder and a substantial contributor to maternal morbidity and mortality. In addition to affecting the mother, PPD can have short- and long-term consequences for the infant and partner. The precise etiology of PPD is unknown, but proposed mechanisms include altered regulation of stress response pathways, such as the hypothalamic-pituitary-adrenal

Several studies have highlighted the role that early postnatal levels of allopregnanolone play in the development of the CNS and adult behavior. Changes in allopregnanolone levels related to stress have been observed during early postnatal periods, and perinatal stress has been linked to neuropsychiatric disorders. The alteration of early postnatal allopregnanolone levels in the first weeks of life

The presence of side effects during pharmacological treatment is unfortunately a quite common problem. In this review, we focused our attention on adverse events related to 5 alpha-reductase (5α-R) inhibitors (i.e., finasteride and dutasteride), approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia (AGA). Although these drugs are generally well tolerated, many reports

In the 1980s particular endogenous metabolites of progesterone and of deoxycorticosterone were revealed to be potent, efficacious, positive allosteric modulators (PAMs) of the GABAA receptor (GABAAR). These reports were followed by the discovery that such steroids may be synthesised not only in peripheral endocrine glands, but locally in the central nervous system (CNS), to potentially act as paracrine

Cognitive dysfunction, dementia and Alzheimer's disease (AD) are increasing as the population worldwide ages. Therapeutics for these conditions is an unmet need. This review focuses on the role of the positive GABA-A receptor modulating steroid allopregnanolone (APα), it's role in underlying mechanisms for impaired cognition and of AD, and to determine options for therapy of AD. On one hand, APα given

The kynurenine pathway (KP) is the dominant pathway for tryptophan degradation in the mammalian body and emerging evidence suggests that acute episodes of sleep deprivation (SD) disrupt tryptophan metabolism via the KP. Increases in the neuroactive KP metabolite kynurenic acid (KYNA) during pregnancy may lead to a higher risk for disrupted neurodevelopment in the offspring. As pregnancy is a critical

Recent FDA approval of an allopregnanolone-based treatment specifically for postpartum depression, brexanolone, now commercially called Zulresso®, is an exciting development for patients and families impacted by postpartum depression and allows us to start asking questions about why and how this compound is so effective. Allopregnanolone is a neuroactive steroid, or neurosteroid, which can be synthesized

The recent FDA approval of the neurosteroid, brexanolone (allopregnanolone), as a treatment for women with postpartum depression, and successful trials of a related neuroactive steroid, SGE-217, for men and women with major depressive disorder offer the hope of a new era in treating mood and anxiety disorders based on the potential of neurosteroids as modulators of brain function. This review considers

Chronic stress increases the probability of receiving an anxiety, depression, or chronic illness diagnosis. Pharmacological interventions that reduce the behavioral and physiological effects of chronic stress in animal models may represent novel approaches for the treatment of stress-related psychiatric disorders. Here, we examined the effects of cyclooxygenase-2 (COX-2) inhibition on anxiety-like

We focused on individual risk by examining childhood adversity and current psychiatric symptoms in a sample of 100 college students genotyped for both the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF). Naturally occurring allelic variation in 5-HTTLPR (short/long) and BDNF (valine/methionine) have been strongly implicated in stress-related psychiatric risk, but the

Tissue plasminogen activator (tPA) is a serine protease involved in cleavage of neurotrophic factors. In addition, tPA and neuroserpin can also directly bind to low density lipoprotein receptor-related protein 1 (LRP1), promoting neurogenesis and neurite outgrowth. Given both the cleavage and non-cleavage actions of the fibrinolytic system are crucial in neurological functions, the present study, for

Stress and anxiety have intertwined behavioral and neural underpinnings. These commonalities are critical for understanding each state, as well as their mutual interactions. Grasping the mechanisms underlying this bidirectional relationship will have major clinical implications for managing a wide range of psychopathologies. After briefly defining key concepts for the study of stress and anxiety in

The importance of a precisely coordinated neuroendocrine, autonomic, and behavioral stress response was a primary theme at the Stress Neurobiology Workshop 2018, held in the beautiful setting of Banff Provincial Park in Alberta, Canada. Much of the research featured at this meeting reinforced the importance of appropriately responding to stress in order to avoid various neuropsychiatric pathologies

The mechanisms underlying the protective effects of remote ischemic preconditioning (RIPC) are not presently clear. Recent studies in experimental models suggest the involvement of the autonomic nervous system (ANS) in cardioprotection. The aim of this study was to investigate the changes in ANS in healthy young volunteers divided into RIPC (n = 22) or SHAM (n = 18) groups. RIPC was induced by 1 cycle

Exposure to prolonged, unpredictable stress leads to glucocorticoids-mediated long-lasting neuroendocrine abnormalities associated with emotional and cognitive impairments. Excessive levels of serum glucocorticoids (cortisol in humans, corticosterone in rodents) contribute notably to deficits in working memory (WM), a task which heavily relies on functional interactions between the medial prefrontal

Emotional stress responses, encompassing both stress reactivity and regulation, have been shown to differ between men and women, but the neural networks supporting these processes remain unclear. The current study used functional neuroimaging (fMRI) to investigate sex differences in neural responses during stress and the sex-specific relationships between these responses and emotional stress responses

Alterations to the mesolimbic dopamine (DA) system are thought to underlie dysfunctional reward processing in stress-related psychiatric disorders. Using in vivio microdialysis in awake freely moving mice, we assessed the effects of stress on the motivational and neurochemical correlates underlying conditioned approach behavior for palatable food in the non-deprived mouse. Mice trained to approach

The impact of psychological stressors on the progression of motor and non-motor disturbances observed in Parkinson's disease (PD) has received little attention. Given that PD likely results from many different environmental "hits", we were interested in whether a chronic unpredictable stressor regimen would act additively or possibly even synergistically to augment the impact of the toxicant, paraquat

Stress exposure is an important risk factor for psychiatric and cardiovascular disorders. Two phenotypes related to coping with stress can be observed in rodents that experience chronic social defeat stress (SDS): susceptible, showing social avoidance and behavioral changes related to depression, and resilient, showing none of these alterations. Moreover, a strong correlation exists between depression

Background There is inconsistency in the literature regarding the nature of hypothalamic-pituitary-adrenal (HPA) axis functionality in post-traumatic stress disorder (PTSD). Purpose The review aimed to investigate HPA axis functionality via the diurnal profile of cortisol as it relates to PTSD. Methods The authors conducted a systematic review of the literature from June 2017 - March 2019 in accordance

The endocannabinoid (eCB) system has been implicated in a variety of physiological functions due to abundant expression of its receptors and endogenous ligands in the central nervous system. Substantial progress has been made in understanding how the eCB system influences the brain norepinephrine (NE) system, an important neurochemical target in the continued development of new therapies for stress-induced

Addiction remains a significant public health concern. Despite numerous public health initiatives, many parents continue to use substances during the prenatal and postpartum period. While stress has been implicated in the maintenance of substance use disorders more generally, we propose that parenting stress specifically increases vulnerability to substance use in adults caring for young children.

Stress is known to elicit contrasting patterns of plasticity in the amygdala and hippocampus. While chronic stress leads to neuronal atrophy in the rodent hippocampus, it has the opposite effect in the basolateral amygdala (BLA). Further, even a single episode of acute stress is known to elicit delayed effects in the amygdala. For example, 2 h of immobilisation stress has been shown to cause a delayed

Transposable elements make up a much larger portion of the genome than protein-coding genes, yet we know relatively little about their function in the human genome. However, we are beginning to more fully understand their role in brain development, neuroinflammation, and adaptation to environmental insults such as stress. For instance, glucocorticoid receptor activation regulates transposable elements

Stress is an inevitable part of life that can profoundly impact social and emotional functioning, contributing to the development of psychiatric disease. One key component of emotion and social processing is facial expressions, which humans can readily detect and react to even without conscious awareness. Facial expressions have been the focus of philosophic and scientific interest for centuries. Historically

Objectives To examine the role of the hippocampus in stress regulation in older adults with amnestic mild cognitive impairment (aMCI). Methods This study combined resting-state functional MRI, structural MRI, self-reported chronic stress exposure, and an electrocardiography-based acute stress protocol to compare aMCI group (n = 17) to their cognitively healthy counterparts (HC, n = 22). Results For

Ensembles of principal neurons in the basolateral amygdala (BLA) generate the initial engrams for fear memories, while projections from the BLA to the medial prefrontal cortex (mPFC) are essential for the encoding, transfer and storage of remote fear memories. We tested the effects of chronic pain on remote fear memories in mice. Male mice underwent classic fear conditioning by pairing a single tone

The synaptic networks in the amygdala have been the subject of intense interest in recent times, primarily because of the role of this structure in emotion. Fear and its extinction depend on the workings of these networks, with particular interest in extinction because of its potential to ameliorate adverse symptoms associated with post-traumatic stress disorder. Here we place emphasis on the extinction

Depression is a debilitating mental disease, characterized by persistent low mood and anhedonia. Stress represents a major environmental risk factor for depression; the complex interaction of stress with genetic factors results in different individual vulnerability or resilience to the disorder. Dysfunctions of the glutamate system have a primary role in depression. Clinical neuroimaging studies have

This perspective highlights research presented as part of the symposium entitled, "Stress and Glucocorticoid Modulation of Feeding and Metabolism" at the 2018 Neurobiology of Stress Workshop held in Banff, AB, Canada. The symposium comprised five researchers at different career stages who each study different aspects of the interaction between the stress response and metabolic control. Their collective