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Article ; Online: Intrahypothalamic effects of oxytocin on PVN CRH neurons in response to acute stress.

Pati, Dipa / Krause, Eric G / Frazier, Charles J

Current opinion in endocrine and metabolic research

2022 Volume 26

Abstract: Much of the centrally available oxytocin (OT) is synthesized in magnocellular neurons located in the paraventricular nucleus of the hypothalamus. This same area is home to parvocellular corticotropin-releasing hormone (CRH) synthesizing neurons that ... ...

Abstract	Much of the centrally available oxytocin (OT) is synthesized in magnocellular neurons located in the paraventricular nucleus of the hypothalamus. This same area is home to parvocellular corticotropin-releasing hormone (CRH) synthesizing neurons that regulate activation of the hypothalamic-pituitary-adrenal (HPA) axis. A large body of data indicates that complex interactions between these systems inextricably link central OT signaling with the neuroendocrine response to stress. This review focuses on a small but diverse set of cellular and synaptic mechanisms that have been proposed to underlie intrahypothalamic OT/CRF interactions during the response to acute stress.
Language	English
Publishing date	2022-07-19
Publishing country	England
Document type	Journal Article
ISSN	2451-9650
ISSN (online)	2451-9650
DOI	10.1016/j.coemr.2022.100382
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Sodium Intake and Disease: Another Relationship to Consider.

Baumer-Harrison, Caitlin / Breza, Joseph M / Sumners, Colin / Krause, Eric G / de Kloet, Annette D

Nutrients

2023 Volume 15, Issue 3

Abstract: ... Sodium ( ... ...

Abstract	Sodium (Na
MeSH term(s)	Humans ; Taste/physiology ; Appetite/physiology ; Sodium Chloride, Dietary/adverse effects ; Sodium ; Hypertension/etiology
Chemical Substances	Sodium Chloride, Dietary ; Sodium (9NEZ333N27)
Language	English
Publishing date	2023-01-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15030535
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Article ; Online: Oxytocin treatment for alcoholism: Potential neurocircuitry targets.

Peris, Joanna / Steck, Madeline R / Krause, Eric G

Neuropharmacology

2020 Volume 171, Page(s) 108091

Abstract: Oxytocin (OT) has gained considerable interest in recent years as a potential treatment for alcoholism and other substance use disorders. Evidence continues to mount that OT administered either centrally, peripherally or intranasally can decrease ethanol ...

Abstract	Oxytocin (OT) has gained considerable interest in recent years as a potential treatment for alcoholism and other substance use disorders. Evidence continues to mount that OT administered either centrally, peripherally or intranasally can decrease ethanol intake in both humans and animal models. The potential mechanisms for the ability of OT to decrease ethanol reward, and importantly, cue- and stress-induced ethanol relapse, are explored by reviewing the specific neuronal circuits involved in mediating these actions and their sensitivity to OT. In addition to dopamine neurons that project from ventral tegmental area (VTA) to nucleus accumbens (NAc) to signal positively reinforcing events, OT receptors (OxTR) are also expressed by dopamine neurons that project from VTA to brain regions that can convey aversive properties of a stimulus. Moreover, OxTR are expressed by non-dopaminergic neurons in the VTA, such as GABA and glutamate neurons, which can both modulate the activity of dopamine VTA neurons locally (in opposite directions) or can project to other brain regions, including the NAc, where it can alter either positive reinforcement or aversion caused by ethanol. The ability of OT to regulate limbic circuitry and the hypothalamic-pituitary-adrenal axis is discussed as a potential mechanism for the ability of OT to inhibit ethanol-induced negative reinforcement. Together, understanding the diversity and complexity of OT regulation of ethanol reward may contribute to more effective use of OT as pharmacotherapy for alcohol use disorder. This article is part of the special issue on Neuropeptides.
MeSH term(s)	Alcoholism/drug therapy ; Alcoholism/physiopathology ; Animals ; Dopaminergic Neurons/drug effects ; Humans ; Nerve Net/drug effects ; Nerve Net/physiopathology ; Oxytocin/therapeutic use ; Signal Transduction/drug effects
Chemical Substances	Oxytocin (50-56-6)
Language	English
Publishing date	2020-04-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2020.108091
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Article ; Online: Brain Angiotensin Type-1 and Type-2 Receptors in Physiological and Hypertensive Conditions: Focus on Neuroinflammation.

Elsaafien, Khalid / de Kloet, Annette D / Krause, Eric G / Sumners, Colin

Current hypertension reports

2020 Volume 22, Issue 7, Page(s) 48

Abstract: Purpose of review: To review recent data that suggest opposing effects of brain angiotensin type-1 (AT: Recent findings: The renin-angiotensin system (RAS) plays an important role in regulating cardiovascular physiology. This includes brain ... ...

Abstract	Purpose of review: To review recent data that suggest opposing effects of brain angiotensin type-1 (AT Recent findings: The renin-angiotensin system (RAS) plays an important role in regulating cardiovascular physiology. This includes brain AT
MeSH term(s)	Angiotensin I ; Brain/metabolism ; Humans ; Hypertension ; Receptor, Angiotensin, Type 1/metabolism ; Receptor, Angiotensin, Type 2/metabolism ; Receptors, Angiotensin
Chemical Substances	Receptor, Angiotensin, Type 1 ; Receptor, Angiotensin, Type 2 ; Receptors, Angiotensin ; Angiotensin I (9041-90-1)
Language	English
Publishing date	2020-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-020-01062-0
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Article ; Online: Dendritic osmosensors modulate activity-induced calcium influx in oxytocinergic magnocellular neurons of the mouse PVN.

Sheng, Wanhui / Harden, Scott W / Tan, Yalun / Krause, Eric G / Frazier, Charles J

eLife

2021 Volume 10

Abstract: Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates that the relationship between somatic activity and dendritic release is not ... ...

Abstract	Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates that the relationship between somatic activity and dendritic release is not constant, but the mechanisms through which this relationship can be modulated are not completely understood. Here, we use a combination of electrical and optical recording techniques to quantify activity-induced calcium influx in proximal vs. distal dendrites of oxytocinergic magnocellular neurons located in the paraventricular nucleus of the hypothalamus (OT-MCNs). Results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes; however, activity-induced dendritic calcium influx can be robustly regulated by both osmosensitive and non-osmosensitive ion channels located along the dendritic membrane. Overall, this study reveals that dendritic conductivity is a dynamic and endogenously regulated feature of OT-MCNs that is likely to have substantial functional impact on central oxytocin release.
MeSH term(s)	Action Potentials ; Animals ; Calcium Signaling ; Dendrites/metabolism ; Electric Impedance ; Female ; Genes, Reporter ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Male ; Mice, Transgenic ; Microscopy, Fluorescence, Multiphoton ; Osmoregulation ; Oxytocin/metabolism ; Paraventricular Hypothalamic Nucleus/cytology ; Paraventricular Hypothalamic Nucleus/metabolism ; Receptors, GABA-A/metabolism ; Time Factors ; Red Fluorescent Protein
Chemical Substances	Luminescent Proteins ; Receptors, GABA-A ; Oxytocin (50-56-6)
Language	English
Publishing date	2021-07-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.63486
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Article ; Online: Identification and three-dimensional reconstruction of oxytocin receptor expressing astrocytes in the rat and mouse brain.

Althammer, Ferdinand / Krause, Eric G / de Kloet, Anette D / Smith, Justin / Grinevich, Valery / Charlet, Alexandre / Stern, Javier E

STAR protocols

2022 Volume 3, Issue 1, Page(s) 101160

Abstract: Here, we present a step-by-step protocol for three-dimensional reconstruction of astrocyte morphology, applied to the central amygdala oxytocin receptor-expressing astrocytes. This includes RNAse-free perfusion, combination of RNAscope and ... ...

Abstract	Here, we present a step-by-step protocol for three-dimensional reconstruction of astrocyte morphology, applied to the central amygdala oxytocin receptor-expressing astrocytes. This includes RNAse-free perfusion, combination of RNAscope and immunohistochemistry, and confocal imaging. This protocol provides detailed information about tissue handling and a comprehensive description of the RNAScope technique to label rat and mouse oxytocin receptor mRNA. We also describe three-dimensional reconstruction that allows the assessment of more than 70 different cellular parameters, powerful for studying astrocyte morphology and astrocyte-astrocyte interactions. For complete details on the use and execution of this protocol, please refer to Wahis et al. (2021) and Althammer et al. (2020).
MeSH term(s)	Animals ; Astrocytes ; Central Amygdaloid Nucleus ; Imaging, Three-Dimensional/methods ; Immunohistochemistry ; Mice ; Rats ; Receptors, Oxytocin/genetics
Chemical Substances	Receptors, Oxytocin
Language	English
Publishing date	2022-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2022.101160
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Article ; Online: Oxytocin and cardiometabolic interoception: Knowing oneself affects ingestive and social behaviors.

Smith, Justin A / Eikenberry, Sophia A / Scott, Karen A / Baumer-Harrison, Caitlin / de Lartigue, Guillaume / de Kloet, Annette D / Krause, Eric G

Appetite

2022 Volume 175, Page(s) 106054

Abstract: Maintaining homeostasis while navigating one's environment involves accurately assessing and interacting with external stimuli while remaining consciously in tune with internal signals such as hunger and thirst. Both atypical social interactions and ... ...

Abstract	Maintaining homeostasis while navigating one's environment involves accurately assessing and interacting with external stimuli while remaining consciously in tune with internal signals such as hunger and thirst. Both atypical social interactions and unhealthy eating patterns emerge as a result of dysregulation in factors that mediate the prioritization and attention to salient stimuli. Oxytocin is an evolutionarily conserved peptide that regulates attention to exteroceptive and interoceptive stimuli in a social environment by functioning in the brain as a modulatory neuropeptide to control social behavior, but also in the periphery as a hormone acting at oxytocin receptors (Oxtr) expressed in the heart, gut, and peripheral ganglia. Specialized sensory afferent nerve endings of Oxtr-expressing nodose ganglia cells transmit cardiometabolic signals via the Vagus nerve to integrative regions in the brain that also express Oxtr(s). These brain regions are influenced by vagal sensory pathways and coordinate with external events such as those demanding attention to social stimuli, thus the sensations related to cardiometabolic function and social interactions are influenced by oxytocin signaling. This review investigates the literature supporting the idea that oxytocin mediates the interoception of cardiovascular and gastrointestinal systems, and that the modulation of this awareness likewise influences social cognition. These concepts are then considered in relation to Autism Spectrum Disorder, exploring how atypical social behavior is comorbid with cardiometabolic dysfunction.
Language	English
Publishing date	2022-04-18
Publishing country	England
Document type	Journal Article
ZDB-ID	1461347-5
ISSN	1095-8304 ; 0195-6663
ISSN (online)	1095-8304
ISSN	0195-6663
DOI	10.1016/j.appet.2022.106054
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Article ; Online: Alleviating Hypertension by Selectively Targeting Angiotensin Receptor-Expressing Vagal Sensory Neurons.

Baumer-Harrison, Caitlin / Elsaafien, Khalid / Johnson, Dominique N / Peñaloza Aponte, Jesus D / de Araujo, Alan / Patel, Sagar / Bruce, Erin B / Harden, Scott W / Frazier, Charles J / Scott, Karen A / de Lartigue, Guillaume / Krause, Eric G / de Kloet, Annette D

The Journal of neuroscience : the official journal of the Society for Neuroscience

2024 Volume 44, Issue 9

Abstract: Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a ... ...

Abstract	Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a receptors (referred to as NG
MeSH term(s)	Mice ; Male ; Female ; Animals ; Desoxycorticosterone Acetate/pharmacology ; Hypertension ; Solitary Nucleus/physiology ; Sensory Receptor Cells ; Blood Pressure/physiology ; Phenylephrine/pharmacology ; Ion Channels ; Red Fluorescent Protein
Chemical Substances	tdTomato ; Desoxycorticosterone Acetate (6E0A168OB8) ; Phenylephrine (1WS297W6MV) ; Piezo1 protein, mouse ; Ion Channels ; Red Fluorescent Protein
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1154-23.2023
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Article: Overexpression of angiotensin converting enzyme 2 reduces anxiety-like behavior in female mice

de Kloet, Annette D / Cahill, Karlena M / Scott, Karen A / Krause, Eric G

Physiology & behavior. 2020 Oct. 01, v. 224

2020

Abstract: Accumulating evidence has revealed an intricate role for the renin-angiotensin system (RAS) in the progression or alleviation of stress-related disorders. Along these lines, the ‘pro-stress’ actions of angiotensin-II (Ang-II) are largely thought to be ... ...

Abstract	Accumulating evidence has revealed an intricate role for the renin-angiotensin system (RAS) in the progression or alleviation of stress-related disorders. Along these lines, the ‘pro-stress’ actions of angiotensin-II (Ang-II) are largely thought to be mediated by the angiotensin type-1a receptor (AT1aR). On the other hand, a counter regulatory limb of the RAS that depends on the conversion of Ang-II to angiotensin-(1–7) by angiotensin-converting enzyme 2 (ACE2) has been postulated to exert stress-dampening actions. We have previously found that augmenting ACE2 activity is potently anxiolytic and blunts stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis in male mice. Whether increasing ACE2 activity also relieves stress and anxiety in females has not yet been determined. Consequently, this series of experiments tests the hypothesis that augmenting ACE2 expression is anxiolytic and dampens the activity of the HPA axis in female mice. Using the Cre-LoxP system, we generated female mice that were homo-, heterozygous or wild-type for a mutated allele resulting in ubiquitous overexpression of ACE2. Next, we used qPCR to determine that levels of ACE2 mRNA isolated from central and peripheral tissues was dependent on genotype. That is, mice homo- and heterozygous for the ACE2 overexpression had significantly greater levels of ACE2 mRNA relative to littermate matched wild-type controls. Interestingly, anxiety-like behavior as determined by the elevated plus maze, light-dark box and novelty-induced hypophagia tests was also affected by genotype. Specifically, ACE2 overexpression significantly decreased anxiety-like behavior in paradigms dependent on approach-avoidance conflict and novelty; however, locomotor activity was similar amongst the genotypes. Final experiments measured plasma corticosterone to evaluate whether increasing ACE2 alters basal and/or stress-induced HPA axis activity. In contrast to what was previously found in males, increasing ACE2 expression had no effect on plasma corticosterone under basal conditions or subsequent to an acute restraint challenge. Collectively, these results suggest that increasing ACE2 expression potently elicits anxiolysis in female mice without altering HPA axis activity.
Keywords	alleles ; angiotensin II ; anxiety ; corticosterone ; elevated plus-maze test ; females ; heterozygosity ; locomotion ; males ; peptidyl-dipeptidase A ; renin-angiotensin system ; tranquilizers ; undereating
Language	English
Dates of publication	2020-1001
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-light
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2020.113002
Database	NAL-Catalogue (AGRICOLA)

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Article: Oxytocin and cardiometabolic interoception: Knowing oneself affects ingestive and social behaviors

Smith, Justin A. / Eikenberry, Sophia A. / Scott, Karen A. / Harrison, Caitlin B. / de Lartigue, Guillaume / de Kloet, Annette D. / Krause, Eric G.

Appetite. 2022 Apr. 14,

2022

Abstract	Maintaining homeostasis while navigating one's environment involves accurately assessing and interacting with external stimuli while remaining consciously in tune with internal signals such as hunger and thirst. Both atypical social interactions and unhealthy eating patterns emerge as a result of dysregulation in factors that mediate the prioritization and attention to salient stimuli. Oxytocin is an evolutionarily conserved peptide that regulates attention to exteroceptive and interoceptive stimuli in a social environment by functioning in the brain as a modulatory neuropeptide to control social behavior, but also in the periphery as a hormone acting at oxytocin receptors (Oxtr) expressed in the heart, gut, and peripheral ganglia. Specialized sensory afferent nerve endings of Oxtr-expressing nodose ganglia cells transmit cardiometabolic signals via the Vagus nerve to integrative regions in the brain that also express Oxtr(s). These brain regions are influenced by vagal sensory pathways and coordinate with external events such as those demanding attention to social stimuli, thus the sensations related to cardiometabolic function and social interactions are influenced by oxytocin signaling. This review investigates the literature supporting the idea that oxytocin mediates the interoception of cardiovascular and gastrointestinal systems, and that the modulation of this awareness likewise influences social cognition. These concepts are then considered in relation to Autism Spectrum Disorder, exploring how atypical social behavior is comorbid with cardiometabolic dysfunction.
Keywords	autism ; brain ; cognition ; gastrointestinal system ; heart ; homeostasis ; hunger ; nerve tissue ; neuropeptides ; oxytocin ; prioritization ; social behavior ; social environment ; thirst ; vagus nerve
Language	English
Dates of publication	2022-0414
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	764440-1
ISSN	0195-6663
ISSN	0195-6663
DOI	10.1016/j.appet.2022.106054
Database	NAL-Catalogue (AGRICOLA)

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