Principles of synaptic encoding of brainstem circadian rhythms.

Circadian regulation of autonomic tone and reflex pathways pairs physiological processes with the daily light cycle. However, the underlying mechanisms mediating these changes on autonomic neurocircuitry are only beginning to be understood. The brainstem nucleus of the solitary tract (NTS) and adjacent nuclei, including the area postrema and dorsal motor nucleus of the vagus, are key candidates for rhythmic control of some aspects of the autonomic nervous system.

Metabolic dysfunctions following chronic oral corticosterone are modified by adolescence and sex in mice.

Adolescence is a period of development in which shifts in responses to glucocorticoids is well-documented. Obesity and metabolic syndrome are substantial health issues whose rates continue to rise in both adult and adolescent populations. Though many interacting factors contribute to these dysfunctions, how these shifts in glucocorticoid responses may be related remain unknown.

Circadian desynchronization disrupts physiological rhythms of prefrontal cortex pyramidal neurons in mice.

Disruption of circadian rhythms, such as shift work and jet lag, are associated with negative physiological and behavioral outcomes, including changes in affective state, learning and memory, and cognitive function. The prefrontal cortex (PFC) is heavily involved in all of these processes. Many PFC-associated behaviors are time-of-day dependent, and disruption of daily rhythms negatively impacts these behavioral outputs.

Circadian regulation of glutamate release pathways shapes synaptic throughput in the brainstem nucleus of the solitary tract (NTS).

Circadian regulation of autonomic reflex pathways pairs physiological function with the daily light cycle. The brainstem nucleus of the solitary tract (NTS) is a key candidate for rhythmic control of the autonomic nervous system. Here we investigated circadian regulation of NTS neurotransmission and synaptic throughput using patch-clamp electrophysiology in brainstem slices from mice.

Profiling rhythmicity of bile salt hydrolase activity in the gut lumen with a rapid fluorescence assay.

Diurnal rhythmicity of cellular function is key to survival for most organisms on Earth. Many circadian functions are driven by the brain, but regulation of a separate set of peripheral rhythms remains poorly understood. The gut microbiome is a potential candidate for regulation of host peripheral rhythms, and this study sought to specifically examine the process of microbial bile salt biotransformation.

Brain-derived neurotrophic factor Val66Met polymorphism modulates the effects of circadian desynchronization on activity and sleep in male mice.

Introduction: Understanding how environmental interact challenges with genetic predispositions modulate health and wellbeing is an important area of biomedical research. Circadian rhythms play an important role in coordinating the multitude of cellular and tissue processes that organisms use to predict and adapt to regular changes in the environment, and robust circadian rhythms contribute to optimal physiological and behavioral responses to challenge. However, artificial lighting and modern round-the-clock lifestyles can disrupt the circadian system, leading to desynchronization of clocks throughout the brain and body.

Chronic hypothalamic-pituitary-adrenal axis disruption alters glutamate homeostasis and neural responses to stress in male C57Bl6/N mice.

It is now well-established that stress elicits brain- and body-wide changes in physiology and has significant impacts on many aspects of health. The hypothalamic-pituitary-adrenal (HPA) axis is the major neuroendocrine system mediating the integrated response to stress. Appropriate engagement and termination of HPA activity enhances survival and optimizes physiological and behavioral responses to stress, while dysfunction of this system is linked to negative health outcomes such as depression, anxiety, and post-traumatic stress disorder.

Corticosterone inhibits vagal afferent glutamate release in the nucleus of the solitary tract via retrograde endocannabinoid signaling.

Circulating blood glucocorticoid levels are dynamic and responsive to stimuli that impact autonomic function. In the brain stem, vagal afferent terminals release the excitatory neurotransmitter glutamate to neurons in the nucleus of the solitary tract (NTS). Vagal afferents integrate direct visceral signals and circulating hormones with ongoing NTS activity to control autonomic function and behavior.

Interleukin-6 (IL-6) response to a simulated night-shift schedule is modulated by brain-derived neurotrophic factor () genotype.

The gene contains a polymorphism (Val66Met) that influences sleep and may be associated with more flexible adaptation to circadian misalignment. Fifteen adult men (10 Val/Val homozygotes, 5 Val/Met heterozygotes) participated in a laboratory study involving two 5 d cycles of simulated night shifts. Circulating interleukin-6 (IL-6) was measured from plasma, sleep was recorded polysomnographically, and performance was measured using a psychomotor vigilance test.

Effect of Aging on Daily Rhythms of Lactate Metabolism in the Medial Prefrontal Cortex of Male Mice.

Aging is associated with reduced amplitude and earlier timing of circadian (daily) rhythms in sleep, brain function, and behavior. We examined whether age-related circadian dysfunction extends to the metabolic function of the brain, particularly in the prefrontal cortex (PFC). Using enzymatic amperometric biosensors, we recorded lactate concentration changes in the PFC in Young (7 mos) and Aged (19 mos) freely-behaving C57BL/6N male mice.

Circadian desynchronization alters metabolic and immune responses following lipopolysaccharide inoculation in male mice.

Metabolism and inflammation are linked at many levels. Sickness behaviors are elicited by the immune system's response to antigenic stimuli, and include changes in feeding and metabolism. The immune system is also regulated by the circadian (daily) clock, which generates endogenous rhythms, and synchronizes these rhythms to the light-dark cycle.

The hypothalamic-pituitary-adrenal axis as a substrate for stress resilience: Interactions with the circadian clock.

Stress, primarily processed via the hypothalamic-pituitary-adrenal (HPA) axis, engages biological pathways throughout the brain and body which promote adaptation and survival to changing environmental demands. Adaptation to environmental challenges is compromised when these pathways are no longer functioning optimally. The physiological and behavioral mechanisms through which HPA axis function influences stress adaptation and resilience are not fully elucidated.

Circadian Regulation of the Brain and Behavior: A Neuroendocrine Perspective.

Neuroendocrine systems are key regulators of brain and body functions, providing an important nexus between internal states and the external world, which then modulates appropriate behavioral outputs. Circadian (daily) rhythms are endogenously generated rhythms of approximately 24 h that help to synchronize internal physiological processes and behavioral states to the external environmental light-dark cycle. Given the importance of timing (hours, days, annual) in many different neuroendocrine axes, understanding how the circadian timing system regulates neuroendocrine function is particularly critical.

Role of corticosterone in altered neurobehavioral responses to acute stress in a model of compromised hypothalamic-pituitary-adrenal axis function.

An organism's capacity to cope with stressful experiences is dependent on its ability to appropriately engage central and peripheral systems, such as the hypothalamic-pituitary-adrenal (HPA) axis, to adapt to changing environmental demands. The HPA axis is a primary neuroendocrine mediator of neural and behavioral responses to stress, and dysfunction of this system is linked to increased risk for developing mental health disorders such as depression, anxiety, and post-traumatic stress disorder. However, the mechanisms by which dysregulated HPA function results in abnormal behavioral responses to stress are poorly understood.

Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1.

Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults and plays a critical role in brain health and disease. We report that the core circadian clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism and a lesser non-cell-autonomous signal from neurons.

Stress: Common themes toward the next frontier.

"Stress is complicated". A phrase uttered by many a stress researcher. This is true, from the vast array of stimuli considered "stressors" to the interactive and hormetic nature of the molecular, cellular, endocrine, and behavioral responses generated by such stressors.

Chronic Corticosterone Treatment During Adolescence Has Significant Effects on Metabolism and Skeletal Development in Male C57BL6/N Mice.

Glucocorticoids are potent modulators of metabolic and behavioral function. Their role as mediators in the "stress response" is well known, but arguably their primary physiological function is in the regulation of cellular and organismal metabolism. Disruption of normal glucocorticoid function is linked to metabolic disease, such as Cushing syndrome.

Nuclear receptor REV-ERBα mediates circadian sensitivity to mortality in murine vesicular stomatitis virus-induced encephalitis.

Certain components and functions of the immune system, most notably cytokine production and immune cell migration, are under circadian regulation. Such regulation suggests that circadian rhythms may have an effect on disease onset, progression, and resolution. In the vesicular stomatitis virus (VSV)-induced encephalitis model, the replication, caudal penetration, and survivability of intranasally applied VSV depends on both innate and adaptive immune mechanisms.

Sustained glucocorticoid exposure recruits cortico-limbic CRH signaling to modulate endocannabinoid function.

Sustained exposure to stress or corticosteroids is known to cause changes in brain endocannabinoid (eCB) signaling, such that tissue contents of the eCBs N-arachidonylethanolamine (AEA) are generally reduced while 2-arachidonoylglycerol (2-AG) levels increase. These changes in eCB signaling are important for many of the aspects of chronic stress, such as anxiety, reward sensitivity and stress adaptation, yet the mechanisms mediating these changes are not fully understood. We have recently found that the stress-related neuropeptide corticotropin-releasing hormone (CRH), acting through the CRH type 1 receptor (CRHR1), can reduce AEA content by increasing its hydrolysis by the enzyme fatty acid amide hydrolase (FAAH) as well as increase 2-AG contents.

Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function.

Obesity is a major public health problem affecting overall physical and emotional well-being. Despite compelling data suggesting an association between obesity and cognitive dysfunction, this phenomenon has received relatively little attention. Neuroimaging studies in obese humans report reduced size of brain regions involved in cognition, but few studies have investigated the cellular processes underlying cognitive decline in obesity or the influence of obesity on cognition in the absence of obesity-related illnesses.

Mechanisms of stress in the brain.

The brain is the central organ involved in perceiving and adapting to social and physical stressors via multiple interacting mediators, from the cell surface to the cytoskeleton to epigenetic regulation and nongenomic mechanisms. A key result of stress is structural remodeling of neural architecture, which may be a sign of successful adaptation, whereas persistence of these changes when stress ends indicates failed resilience. Excitatory amino acids and glucocorticoids have key roles in these processes, along with a growing list of extra- and intracellular mediators that includes endocannabinoids and brain-derived neurotrophic factor (BDNF).