Ilia N Karatsoreos

• PhD
• Professor (Associate) at University of Massachusetts Amherst

Sleep and circadian (daily) rhythms impact nearly all aspects of physiology and are critical for optimal organismal function. Disruption of the clock can lead to significant metabolic disorders, neuropsychiatric illness, and cognitive dysfunction. Our lab has previously shown that environmental circadian desynchronization (ECD) in adults alters the...

Traumatic brain injury (TBI) is an established risk factor for developing neurodegenerative disease. However, how TBI leads from acute injury to chronic neurodegeneration is limited to post-mortem models. There is a lack of connections between in vitro and in vivo TBI models that can relate injury forces to both macroscale tissue damage and brain f...

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...

Life on earth has evolved under a consistent cycle of light and darkness caused by the earth's rotation around its axis. This has led to a 24-hour circadian system in most organisms, ranging all the way from fungi to humans. With the advent of electric light in the 19th century, cycles of light and darkness have drastically changed. Shift workers a...

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...

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, an...

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 electrophys...

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...

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...

From his early work in deciphering how adrenal hormones can enter the brain and impact cellular function to groundbreaking findings uncovering the mechanisms by which steroid hormones affected neuronal structure, Bruce S. McEwen (1938–2020) made an indelible mark on the field of behavioral neuroendocrinology. His work helped to clarify how “good st...

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 electrophys...

Obesity is a global public health problem linked to increased risk for many disorders including diabetes, cardiovascular disease, and even cancer. The World Health Organization estimates almost 2 billion adults worldwide are considered overweight with nearly 600 million of those individuals also being considered obese. How did we get here? The laws...

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 the HPA activity enhances survival an...

Introduction Sleep disorders and ischemic stroke (IS) are large health burdens. Almost half the USA population reports disturbed sleep and 795,000 Americans suffer a stroke annually. Despite dysregulated sleep being a stroke risk factor that can exacerbate injury and prolong recovery, sleep deprivation immediately preceding experimental stroke is n...

Introduction Bacterial cell wall peptidoglycan (PG) and muramyl peptides (MPs), isolated from mammalian brains and urine following sleep deprivation (SD), promote non-rapid eye movement sleep. These PG/MPs likely originate from the host microbiome and have been quantified in neonatal murine brain. PG/MP amounts and dynamics in healthy, adult murine...

Getting a good night's sleep seems a panacea for improving mood and cognition. These subjective impressions are supported by countless studies exploring the impacts of sleep (and sleep loss) on mental health, metabolism, and immune function. Similarly, being "out of phase" with local time, commonly experienced by shift workers of jet-lagged air tra...

The prefrontal cortex (PFC) is heavily involved in cognitive and emotional processes, including working memory, cognition, stress responses, and fear associated behaviors. Many PFC-associated behaviors are time-of-day dependent, and disruption of daily rhythms negatively impacts these behavioral outputs, yet how the disruption of daily rhythms impa...

In order to survive and thrive, organisms must adapt to constantly changing environmental pressures. When there are significant shifts in the environment, the brain and body engage a set of physiological and behavioral countermeasures collectively known as the "stress response". These responses, which include changes at the cellular, systems, and o...

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

The BDNF 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...

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 concentrati...

Introduction Brain Derived Neurotrophic Factor (BDNF) is involved in synaptic plasticity and may be involved in sleep and circadian regulation. The BDNF gene has a single nucleotide polymorphism (Val66Met) resulting in decreased BDNF secretion. The Met allele is associated with reduced nocturnal slow wave activity following sleep loss, and may also...

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. Mo...

Sleep regulation involves IL1 family members, TNF, and circadian clock genes. Previously, we characterized spontaneous sleep and sleep after eight hours of sleep deprivation (SD) ending at zeitgeber time (ZT) 4 and ZT16 in wild type (WT) and IL1 receptor accessory protein (AcP) and brain specific AcP (AcPb) knockout (KO) mice. Herein, we applied RT...

On 2 January 2020, the neuroscience community lost not only a pioneering figure, but also a generous and influential thought leader. Bruce Sherman McEwen, head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at the Rockefeller University, passed away at age 81, following a short illness. A member of the National Academy o...

Stress is a word that is used throughout the world and it has many meanings. Physiologically, cortisol and adrenalin are stress hormones, and the “fight or flight” response is usually the focus of discussions of stress. But that is only part of the story. There are multiple biological mediators besides the adrenal stress hormones that are responsib...

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 behavio...

Chronically elevated levels of glucocorticoids increase food intake, weight gain and adiposity. Similarly, ghrelin, a gut-secreted hormone, is also associated with weight gain, adiposity and increased feeding. Here we sought to determine if corticosterone induced metabolic and behavioral changes require functional ghrelin receptors (GHSR). To do th...

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 beha...

Aging is associated with reduced circadian (daily) rhythm amplitude in physiology and behavior, and decreased function of the prefrontal cortex (PFC). Similar effects are seen in younger mice experiencing circadian desynchrony (CD) caused by exposure to 20h light-dark cycles (T20). Given changes in PFC structure/function, underlying metabolic funct...

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...

Aims: The hypothalamic pituitary adrenal (HPA) axis is the key neuroendocrine mediator of the stress response and controls many aspects of physiology and behavior. We previously showed that experimentally disrupting normal HPA function in mice led to altered neural and behavioral responses to acute stress. When exposed to prolonged or repeated stre...

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 dysfuncti...

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 synergist...

Shift work leads to adverse health outcomes including increased risk of cardiovascular disease. Heart rate (HR) and heart rate variability (HRV) are measures of cardiac autonomic activity and markers of cardiovascular disease and mortality. To investigate the effects of shift work on cardiac autonomic activity, we assessed the influence of simulate...

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 clock protein BMAL1 regulates astrogliosis in a synergistic manner...

"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. This commentary takes the position that stress researchers are poised to make e...

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 synergist...

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’s syndr...

Disruption of the optimal temporal order of bodily processes, such as that experienced in jet lag, increases risk for poor health and illness. The mechanisms underlying these body-wide effects involve daily oscillations in nearly all behavioral and physiological responses. The timekeeping mechanism entails a complex of molecular transcription–trans...

The prominent circadian rhythms of the endocrine system are important for our broader understanding of physiology and behavior, in both health and disease. There is now much evidence that disruptions in the circadian domain, due to either external factors such as shift work or internal factors such as sleep disturbances, can lead to physiological a...

Anecdotally, we all know stress is "complicated", but most stress research is undertaken using incredibly simplified models that may not allow us to fully understand underlying interactive mechanisms that are present in the "real world". This attempt at simplification, while sometimes necessary, may explain some of the difficulties in translating b...

Obesity is a global public health problem linked to increased risk for many disorders including diabetes, cardiovascular disease, and even cancer. The World Health Organization estimates almost two billion adults worldwide are considered overweight with nearly 600 million of those individuals also being considered obese. How did we get here? The la...

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 to be important for many of the aspects of chronic str...

Obesity is a global public health problem linked to increased risk for many disorders including diabetes, cardiovascular disease, and even cancer. The World Health Organization estimates almost two billion adults worldwide are considered overweight with nearly 600 million of those individuals also being considered obese. How did we get here? The la...

Significance In humans, obesity impairs cognition and produces atrophy of brain regions associated with learning and memory, but few studies have investigated the underlying cellular mechanisms. We used a diet-induced model of obesity in rats to study excessive weight gain and found that early stage obesity, before the onset of diabetes or metaboli...

Prolonged stress and repeated activation of the hypothalamic-pituitary-adrenal (HPA) axis can result in many sex-dependent behavioral and metabolic changes in rats, including alterations in feeding behavior and reduced body weight. In adults, these effects of stress can be mimicked by corticosterone, a major output of the hypothalamic-pituitary-adr...

A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by ac...

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, wh...

Sleep has important homeostatic functions, and circadian rhythms organize physiology and behavior on a daily basis to insure optimal function. Sleep deprivation and circadian disruption can be stressors, enhancers of other stressors that have consequences for the brain and many body systems. Whether the origins of circadian disruption and sleep dis...

Organisms react to environmental challenges by activating a coordinated set of brain–body responses known as the stress response. These physiological and behavioral countermeasures are, in large part, regulated by the neuroendocrine hypothalamic–pituitary–adrenal (HPA) axis. Normal functioning of the HPA axis ensures that an organism responds appro...

Significance Obesity and associated metabolic disorders (e.g., cardiovascular disease and type 2 diabetes) are major public health concerns. These disorders result, in part, from hormonal dysregulation, particularly of glucocorticoids (GCs; central regulators of metabolism and adipogenesis). The specific mechanisms by which GCs modulate these proce...

In mammals, one of the most salient outputs of the circadian (daily) clock is the timing of the sleep-wake cycle. Modern industrialized society has led to a fundamental breakdown in the relationship between our endogenous timekeeping systems and the solar day, disrupting normal circadian rhythms. We have argued that disrupted circadian rhythms coul...

Ilia N Karatsoreos Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA Abstract: Circadian (daily) rhythms are pervasive in nature, and expressed in nearly every behavioral and physiological process. In mammals, circadian rhythms are regulated by the master brain clock in the suprachiasmatic nucleus...

Why do some people get sick, and others do not? This basic question, of vulnerability and resilience, is of crucial importance in physical and mental health research. Determining factors that impart resilience, or contribute to vulnerability, could be a turning point in our fundamental understanding of disease. This collection explores current data...

A role for arginine vasopressin in the circadian regulation of voluntary locomotor behavior (wheel running activity) was investigated in the golden hamster, Mesocricetus auratus. Spontaneous nocturnal running was suppressed in a dose-dependent manner by systemic injections of vasopressin, and also in a concentration-dependent manner by microinjecti...

Leptin acts in the hippocampus to enhance cognition, and reduce depression and anxiety. Cognitive and emotional disorders are associated with abnormal hippocampal dendritic spine formation and synaptogenesis. While leptin has been shown to induce synaptogenesis in the hypothalamus, its effects on hippocampal synaptogenesis and the mechanism(s) invo...

Determining the cause of psychiatric disorders is a goal of modern neuroscience, and will hopefully lead to the discovery of treatments to either prevent or alleviate the suffering caused by these diseases. One roadblock to attaining this goal is the realization that neuropsychiatric diseases are rarely due to a single gene polymorphism, environmen...

Studies have indicated significant pubertal-related differences in hormonal stress reactivity. We report here that prepubertal (30d) male rats display a more protracted stress-induced corticosterone response than adults (70d), despite showing relatively similar levels of adrenocorticotropic hormone (ACTH). Additionally, we show that adrenal express...

Obesity is a growing public health problem. Although convenient, the notion that obesity is simply a problem of will power is increasingly antiquated. It is becoming clear that complex interactions of environment, neurohormonal systems, and transgenerational effects directly contribute to obesity. This review highlights data presented at the Societ...

Converging evidence suggests that females and males show different responses to stress; however, little is known about the mechanism underlying the sexually dimorphic effects of stress. In this study, we found that young female rats exposed to 1 week of repeated restraint stress show no negative effects on temporal order recognition memory (TORM),...

The brain is constantly adapting to a changing environment. It detects environmental stimuli, integrates that information with internal states, and engages appropriate behavioral and physiological responses. This process of stability through change is termed "allostasis", and serves as a mechanism by which an organism can adapt to a changing enviro...

Background: Adaptation is key to survival. An organism must adapt to environmental challenges in order to be able to thrive in the environment in which they find themselves. Resilience can be thought of as a measure of the ability of an organism to adapt, and to withstand challenges to its stability. In higher animals, the brain is a key player in...

This chapter discusses how the hippocampus, prefrontal cortex and amygdale are affected by stress, and how these stress-induced changes relate to changes in behavior. Located in the medial temporal lobe, the hippocampus is one of the most plastic and sensitive regions of the brain. It is crucially important in both cognitive function and emotionali...

Stress is a word that is used throughout the world, and it has many meanings. There is good stress and bad stress. Some would prefer to use stress to refer only to the experience and consequences of a situation when one is unable to cope physically or psychologically with the challenge (Cohen et al. 2007; Lazarus and Folkman 1984). © 2012 Springer-...

Metabolic syndrome is a condition that typically includes central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension. Disruption of the hypothalamic-pituitary-adrenal axis, a regulator of corticosterone secretion, occurs in some cases of metabolic syndrome and obesity, and Cushing hypercortisolemia is associated with o...

The hypothalamic suprachiasmatic nucleus (SCN) is the locus of a master clock that regulates circadian rhythms in physiology and behavior. Gonadectomy in male mice lengthens the period of circadian rhythms and increases the day-to-day variability of activity onset time. Both of these responses are rescued by the nonaromatizable androgen dihydrotest...

Circadian (daily) rhythms in physiology and behavior are phylogenetically ancient and are present in almost all plants and animals. In mammals, these rhythms are generated by a master circadian clock in the suprachiasmatic nucleus of the hypothalamus, which in turn synchronizes "peripheral oscillators" throughout the brain and body in almost all ce...

The brain and body need to adapt constantly to changing social and physical environments. A key mechanism for this adaptation is the 'stress response', which is necessary and not negative in and of itself. The term 'stress', however, is ambiguous and has acquired negative connotations. We argue that the concept of allostasis can be used instead to...

Limbic endocannabinoid signaling is known to be sensitive to chronic stress; however, studies investigating the impact of prolonged exposure to glucocorticoid hormones have been limited by the concurrent exposure to the stress of daily injections. The present study was designed to examine the effects of a noninvasive approach to alter plasma cortic...

The prevalence of obesity has rapidly escalated and now represents a major public health concern. Although genetic associations with obesity and related metabolic disorders such as diabetes and cardiovascular disease have been identified, together they account for a small proportion of the incidence of disease. Environmental influences such as chro...

The mechanisms subserving the ability of glucocorticoid signaling within the medial prefrontal cortex (mPFC) to terminate stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis are not well understood. We report that antagonism of the cannabinoid CB(1) receptor locally within the mPFC prolonged corticosterone secretion following...

Gonadal hormones can modulate circadian rhythms in rodents and humans, and androgen receptors are highly localized within the core region of the mouse suprachiasmatic nucleus (SCN) brain clock. Although androgens are known to modulate neural plasticity in other CNS compartments, the role of androgens and their receptors on plasticity in the SCN is...

Corticosteroid stress hormones have a strong impact on the function of prefrontal cortex (PFC), a central region controlling cognition and emotion, though the underlying mechanisms are elusive. We found that behavioral stressor or short-term corticosterone treatment in vitro induces a delayed and sustained potentiation of the synaptic response and...

Circadian (daily) rhythms are present in almost all plants and animals. In mammals, a brain clock located in the hypothalamic suprachiasmatic nucleus maintains synchrony between environmental light/dark cycles and physiology and behavior. Over the past 100 y, especially with the advent of electric lighting, modern society has resulted in a round-th...

Functional interactions between glucocorticoids and the endocannabinoid system have been repeatedly documented; yet, to date, no studies have demonstrated in vivo that glucocorticoid hormones regulate endocannabinoid signaling. We demonstrate that systemic administration of the glucocorticoid corticosterone (3 and 10 mg/kg) resulted in an increase...

The concept of homeostasis is potentially one of the most studied and understood aspects of physiology. Also well known are the effects of threats to homeostasis, known as stressors. It has long been appreciated that the body responds to stressors actively, known as an allostatic response. The classic stress response – the activation of the sympath...

Numerous clinical and experimental studies have linked stress to changes in risk factors associated with the development of physiological syndromes, including metabolic disorders. How different mediators of the stress response, such as corticosterone (CORT), influence these changes in risk remains unclear. Although CORT has beneficial short-term ef...

Numerous clinical and experimental studies have linked stress to changes in risk factors associated with the development of physiological syndromes, including metabolic disorders. How different mediators of the stress response, such as corticosterone (CORT), influence these changes in risk remains unclear. Although CORT has beneficial short-term ef...

The prefrontal cortex (PFC), a key brain region controlling cognition and emotion, is strongly influenced by stress. While chronic stress often produces detrimental effects on these measures, acute stress has been shown to enhance learning and memory, predominantly through the action of corticosteroid stress hormones. We used a combination of elect...

In mammals, it is well established that circadian rhythms in physiology and behavior, including the rhythmic secretion of hormones, are regulated by a brain clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. While SCN regulation of gonadal hormone secretion has been amply studied, the mechanisms whereby steroid hormones affect...

Numerous studies have established that adolescence is marked by substantial changes in stress reactivity and hippocampal function. Glucocorticoid receptors (GRs) in the hippocampus are imperative in corticosterone-dependent gene transcription when glucocorticoid levels are relatively high, such as during periods of stress. As reported previously, i...

Circadian rhythms in physiology and behavior are regulated by a master clock resident in the suprachiasmatic nucleus (SCN) of the hypothalamus, and dysfunctions in the circadian system can lead to serious health effects. This paper reviews the organization of the SCN as the brain clock, how it regulates gonadal hormone secretion, and how androgens...

The suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian clock controlling behavioral and physiological rhythms, including rhythmic secretion of gonadal hormones. Gonadectomy results in marked alteration of circadian behaviors, including lengthened free-running period, decreased precision of daily onset of running, a...

In reaction to acute stress, prepubertal (25-28 days of age) animals demonstrate a prolonged adrenocorticotropic hormone (ACTH) and corticosterone response compared to adults (>65 days of age), while after chronic stress, prepubertal animals show a higher peak ACTH and corticosterone response, but a faster return to baseline compared to adults. Dif...