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Article ; Online: Neuroinflammation May Indeed Be a Major Player in Opioid Use Disorder in Humans.

Karatsoreos, Ilia N

2021 Volume 90, Issue 8, Page(s) 511–512

MeSH term(s)	Humans ; Opioid-Related Disorders/epidemiology ; Receptors, Opioid, mu
Chemical Substances	Receptors, Opioid, mu
Language	English
Publishing date	2021-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2021.08.005
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Article ; Online: Circadian desynchronization disrupts physiological rhythms of prefrontal cortex pyramidal neurons in mice.

Roberts, Brandon L / Karatsoreos, Ilia N

Scientific reports

2023 Volume 13, Issue 1, Page(s) 9181

Abstract: 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 ...

Abstract	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. Yet how disruption of daily rhythms impacts the fundamental function of PFC neurons, and the mechanism(s) by which this occurs, remains unknown. Using a mouse model, we demonstrate that the activity and action potential dynamics of prelimbic PFC neurons are regulated by time-of-day in a sex specific manner. Further, we show that postsynaptic K
MeSH term(s)	Male ; Animals ; Female ; Pyramidal Cells/physiology ; Prefrontal Cortex/physiology ; Neurons/physiology ; Cognition ; Circadian Rhythm/physiology
Language	English
Publishing date	2023-06-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-35898-8
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Article ; Online: Principles of synaptic encoding of brainstem circadian rhythms.

Ragozzino, Forrest J / Karatsoreos, Ilia N / Peters, James H

Experimental physiology

2024

Abstract: 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 ...

Abstract	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. Recent findings have contributed to a working model of circadian regulation in the brainstem which manifests from the transcriptional, to synaptic, to circuit levels of organization. Vagal afferent neurons and the NTS possess rhythmic clock gene expression, rhythmic action potential firing, and our recent findings demonstrate rhythmic spontaneous glutamate release. In addition, postsynaptic conductances also vary across the day producing subtle changes in membrane depolarization which govern synaptic efficacy. Together these coordinated pre- and postsynaptic changes provide nuanced control of synaptic transmission across the day to tune the sensitivity of primary afferent input and likely govern reflex output. Further, given the important role for the brainstem in integrating cues such as feeding, cardiovascular function and temperature, it may also be an underappreciated locus in mediating the effects of such non-photic entraining cues. This short review focuses on the neurophysiological principles that govern NTS synaptic transmission and how circadian rhythms impacted them across the day.
Language	English
Publishing date	2024-02-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1016295-1
ISSN	1469-445X ; 0958-0670
ISSN (online)	1469-445X
ISSN	0958-0670
DOI	10.1113/EP090867
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Article: Circadian Regulation of the Brain and Behavior: A Neuroendocrine Perspective.

Karatsoreos, Ilia N

Current topics in behavioral neurosciences

2019 Volume 43, Page(s) 323–351

Abstract: 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 ... ...

Abstract	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. Similarly, neuroendocrine signals can significantly affect circadian timing, and understanding these mechanisms can provide insights into general concepts of neuroendocrine regulation of brain circuits and behavior. This chapter will review the circadian timing system and its control of two key neuroendocrine systems: the hypothalamic-pituitary-gonadal (HPG) axis and the hypothalamic-pituitary-adrenal (HPA) axis. It will also discuss how outputs from these axes feedback to affect the circadian clock. Given that disruption of circadian timing is a central component of many mental and physical health conditions and that neuroendocrine function is similarly implicated in many of the same conditions, understanding these links will help illuminate potentially shared causality and perhaps lead to a better understanding of how to manipulate these systems when they begin to malfunction.
MeSH term(s)	Circadian Rhythm ; Hypothalamo-Hypophyseal System ; Neurosecretory Systems ; Pituitary-Adrenal System
Language	English
Publishing date	2019-10-05
Publishing country	Germany
Document type	Journal Article
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2019_115
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Article ; Online: Stress: Common themes toward the next frontier.

Karatsoreos, Ilia N

Frontiers in neuroendocrinology

2018 Volume 49, Page(s) 3–7

Abstract: 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 ...

Abstract	"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 even bigger contributions if they begin to shift from investigating the myriad effects of stress on brain and body, and to refocus a larger part of our efforts on more in-depth investigations of common themes in stress biology, with the goal of uncovering potential "universal principles" of stress that may help us better interpret the findings at higher levels of analysis, and provide a structured approach to help breach the next frontiers of stress research.
MeSH term(s)	Animals ; Biomedical Research/standards ; Biomedical Research/trends ; Disease Models, Animal ; Humans ; Stress, Physiological/physiology ; Stress, Psychological/metabolism ; Stress, Psychological/physiopathology
Language	English
Publishing date	2018-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	390985-2
ISSN	1095-6808 ; 0532-7466 ; 0091-3022
ISSN (online)	1095-6808
ISSN	0532-7466 ; 0091-3022
DOI	10.1016/j.yfrne.2018.02.006
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Article ; Online: Brain-body responses to chronic stress: a brief review.

Roberts, Brandon L / Karatsoreos, Ilia N

Faculty reviews

2021 Volume 10, Page(s) 83

Abstract: 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 ... ...

Abstract	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 organismal level, are geared toward protecting homeostasis and adapting physiological operating parameters so as to enable the organism to overcome short-term challenges. It is the shift of these well-organized acute responses to dysregulated chronic responses that leads to pathologies. In a sense, the protective measures become destructive, causing the myriad health problems that are associated with chronic stress. To further complicate the situation, these challenges need not be purely physical in nature. Indeed, psychosocial stressors such as ruminating about challenges at work, resource insecurity, and unstable social environments can engage the very same emergency threat systems and eventually lead to the same types of pathologies that sometimes are described as "burnout" in humans. This short review focuses on very recent empirical work exploring the effects of chronic stress on key brain circuits, metabolism and metabolic function, and immune function.
Language	English
Publishing date	2021-12-16
Publishing country	England
Document type	Journal Article ; Review
ISSN	2732-432X
ISSN (online)	2732-432X
DOI	10.12703/r/10-83
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Article ; Online: Circadian desynchronization disrupts physiological rhythms of prefrontal cortex pyramidal neurons in mice

Brandon L. Roberts / Ilia N. Karatsoreos

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 12

Abstract: Abstract 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) ... ...

Abstract	Abstract 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. Yet how disruption of daily rhythms impacts the fundamental function of PFC neurons, and the mechanism(s) by which this occurs, remains unknown. Using a mouse model, we demonstrate that the activity and action potential dynamics of prelimbic PFC neurons are regulated by time-of-day in a sex specific manner. Further, we show that postsynaptic K+ channels play a central role in physiological rhythms, suggesting an intrinsic gating mechanism mediating physiological activity. Finally, we demonstrate that environmental circadian desynchronization alters the intrinsic functioning of these neurons independent of time-of-day. These key discoveries demonstrate that daily rhythms contribute to the mechanisms underlying the essential physiology of PFC circuits and provide potential mechanisms by which circadian disruption may impact the fundamental properties of neurons.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sleep Deprivation and Circadian Disruption Stress, Allostasis, and Allostatic Load.

McEwen, Bruce S / Karatsoreos, Ilia N

Sleep medicine clinics

2022 Volume 17, Issue 2, Page(s) 253–262

Abstract: 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, ... ...

Abstract	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 travelers, demonstrates that there are both neural and physiologic effects of internal circadian (daily) time being misaligned with external environmental time. This article reviews these areas contextualized using the model of allostasis and allostatic load emphasizing the impact of this "wear and tear" on the brain and body.
MeSH term(s)	Allostasis/physiology ; Brain/physiology ; Humans ; Sleep ; Sleep Deprivation ; Stress, Psychological/psychology
Language	English
Publishing date	2022-04-23
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1556-4088
ISSN (online)	1556-4088
DOI	10.1016/j.jsmc.2022.03.005
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Article: Brain-derived neurotrophic factor Val66Met polymorphism modulates the effects of circadian desynchronization on activity and sleep in male mice.

Phillips, Derrick J / Blaine, Scott / Wallace, Naomi K / Karatsoreos, Ilia N

Frontiers in neuroscience

2023 Volume 16, Page(s) 1013673

Abstract: 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 ... ...

Abstract	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. When coupled with genetic predispositions, circadian desynchronization may compound negative outcomes. Polymorphisms in the brain-derived neurotrophic (BDNF) gene contribute to variations in neurobehavioral responses in humans, including impacts on sleep, with the common Val66Met polymorphism linked to several negative outcomes. Methods: We explored how the Val66Met polymorphism modulates the response to environmental circadian desynchronization (ECD) in a mouse model. ECD was induced by housing adult male mice in a 20 h light-dark cycle (LD10:10; 10 h light, 10 h dark). Sleep and circadian activity were recorded in homozygous (Met) mice and their wild-type (Val) littermates in a standard 24 h LD cycle (LD12:12), then again after 20, 40, and 60 days of ECD. Results: We found ECD significantly affected the sleep/wake timing in Val mice, however, Met mice maintained appropriate sleep timing after 20 days ECD, but not after 40 and 60 days of ECD. In addition, the rise in delta power at lights on was absent in Val mice but was maintained in Met mice. To elucidate the circadian and homeostatic contribution to disrupted sleep, mice were sleep deprived by gentle handling in LD12:12 and after 20 days in ECD. Following 6 h of sleep deprivation delta power was increased for both Val and Met mice in LD12:12 and ECD conditions. However, the time constant was significantly longer in the Val mice during ECD compared to LD12:12, suggesting a functioning but altered sleep homeostat. Discussion: These data suggest the Val66Met mutation is associated with an ability to resist the effects of LD10:10, which may result in carriers suffering fewer negative impacts of ECD.
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2022.1013673
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Article ; Online: Circadian regulation of glutamate release pathways shapes synaptic throughput in the brainstem nucleus of the solitary tract (NTS).

Ragozzino, Forrest J / Peterson, Bree Anne / Karatsoreos, Ilia N / Peters, James H

The Journal of physiology

2023 Volume 601, Issue 10, Page(s) 1881–1896

Abstract: 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 ... ...

Abstract	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. We found that spontaneous quantal glutamate release onto NTS neurons showed strong circadian rhythmicity, with the highest rate of release during the light phase and the lowest in the dark, that were sufficient to drive day/night differences in constitutive postsynaptic action potential firing. In contrast, afferent evoked action potential throughput was enhanced during the dark and diminished in the light. Afferent-driven synchronous release pathways showed a similar decrease in release probability that did not explain the enhanced synaptic throughput during the night. However, analysis of postsynaptic membrane properties revealed diurnal changes in conductance, which, when coupled with the circadian changes in glutamate release pathways, tuned synaptic throughput between the light and dark phases. These coordinated pre-/postsynaptic changes encode nuanced control over synaptic performance and pair NTS action potential firing and vagal throughput with time of day. KEY POINTS: Vagal afferent neurons relay information from peripheral organs to the brainstem nucleus of the solitary tract (NTS) to initiate autonomic reflex pathways as well as providing important controls of food intake, digestive function and energy balance. Vagally mediated reflexes and behaviours are under strong circadian regulation. Diurnal fluctuations in presynaptic vesicle release pathways and postsynaptic membrane conductances provide nuanced control over NTS action potential firing and vagal synaptic throughput. Coordinated pre-/postsynaptic changes represent a fundamental mechanism mediating daily changes in vagal afferent signalling and autonomic function.
MeSH term(s)	Circadian Rhythm/physiology ; Glutamic Acid/metabolism ; Solitary Nucleus/cytology ; Solitary Nucleus/physiology ; Synapses/metabolism ; Neurons, Afferent/metabolism ; Vagus Nerve/cytology ; Vagus Nerve/physiology ; Action Potentials ; Male ; Animals ; Mice ; Nodose Ganglion/metabolism ; Signal Transduction ; Electric Conductivity ; Patch-Clamp Techniques
Chemical Substances	Glutamic Acid (3KX376GY7L) ; Clock protein, mouse (EC 2.3.1.48)
Language	English
Publishing date	2023-04-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP284370
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