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Article ; Online: Hindbrain Adrenergic/Noradrenergic Control of Integrated Endocrine and Autonomic Stress Responses.

Pace, Sebastian A / Myers, Brent

2023 Volume 165, Issue 1

Abstract: Hindbrain adrenergic/noradrenergic nuclei facilitate endocrine and autonomic responses to physical and psychological challenges. Neurons that synthesize adrenaline and noradrenaline target hypothalamic structures to modulate endocrine responses while ... ...

Abstract	Hindbrain adrenergic/noradrenergic nuclei facilitate endocrine and autonomic responses to physical and psychological challenges. Neurons that synthesize adrenaline and noradrenaline target hypothalamic structures to modulate endocrine responses while descending spinal projections regulate sympathetic function. Furthermore, these neurons respond to diverse stress-related metabolic, autonomic, and psychosocial challenges. Accordingly, adrenergic and noradrenergic nuclei are integrative hubs that promote physiological adaptation to maintain homeostasis. However, the precise mechanisms through which adrenaline- and noradrenaline-synthesizing neurons sense interoceptive and exteroceptive cues to coordinate physiological responses have yet to be fully elucidated. Additionally, the regulatory role of these cells in the context of chronic stress has received limited attention. This mini-review consolidates reports from preclinical rodent studies on the organization and function of brainstem adrenaline and noradrenaline cells to provide a framework for how these nuclei coordinate endocrine and autonomic physiology. This includes identification of hindbrain adrenaline- and noradrenaline-producing cell groups and their role in stress responding through neurosecretory and autonomic engagement. Although temporally and mechanistically distinct, the endocrine and autonomic stress axes are complementary and interconnected. Therefore, the interplay between brainstem adrenergic/noradrenergic nuclei and peripheral physiological systems is necessary for integrated stress responses and organismal survival.
MeSH term(s)	Adrenergic Agents ; Norepinephrine/metabolism ; Epinephrine ; Brain Stem/metabolism ; Rhombencephalon/metabolism
Chemical Substances	Adrenergic Agents ; Norepinephrine (X4W3ENH1CV) ; Epinephrine (YKH834O4BH)
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endocr/bqad178
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Article ; Online: Prefrontal representation of affective stimuli: importance of stress, sex, and context.

Wallace, Tyler / Myers, Brent

Cerebral cortex (New York, N.Y. : 1991)

2023 Volume 33, Issue 13, Page(s) 8232–8246

Abstract: Stress-related disorders such as depression and anxiety exhibit sex differences in prevalence and negatively impact both mental and physical health. Affective illness is also frequently accompanied by changes in ventromedial prefrontal cortical (vmPFC) ... ...

Abstract	Stress-related disorders such as depression and anxiety exhibit sex differences in prevalence and negatively impact both mental and physical health. Affective illness is also frequently accompanied by changes in ventromedial prefrontal cortical (vmPFC) function. However, the neurobiology that underlies sex-specific cortical processing of affective stimuli is poorly understood. Although rodent studies have investigated the prefrontal impact of chronic stress, postmortem studies have focused largely on males and yielded mixed results. Therefore, genetically defined population recordings in behaving animals of both sexes were used to test the hypothesis that chronic variable stress (CVS) impairs the neural processing of affective stimuli in the rodent infralimbic region. Here, we targeted expression of a calcium indicator, GCaMP6s, to infralimbic pyramidal cells. In males, CVS reduced infralimbic responses to social interaction and restraint stress but increased responses to novel objects and food reward. In contrast, females did not have CVS-induced changes in infralimbic activity, which was partially dependent on the ovarian status. These results indicate that both male and female vmPFC cells encode social, stress, and reward stimuli. However, chronic stress effects are sex-dependent and behavior-specific. Ultimately, these findings extend the understanding of chronic stress-induced prefrontal dysfunction and indicate that sex is a critical factor for cortical processing of affective stimuli.
MeSH term(s)	Animals ; Male ; Female ; Anxiety/metabolism ; Reward ; Sex Characteristics ; Prefrontal Cortex/physiology ; Stress, Psychological
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhad110
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Article: Cortical-Hypothalamic Integration of Autonomic and Endocrine Stress Responses.

Schaeuble, Derek / Myers, Brent

Frontiers in physiology

2022 Volume 13, Page(s) 820398

Abstract: The prevalence and severity of cardiovascular disease (CVD) are exacerbated by chronic stress exposure. While stress-induced sympathetic activity and elevated glucocorticoid secretion impair cardiovascular health, the mechanisms by which stress- ... ...

Abstract	The prevalence and severity of cardiovascular disease (CVD) are exacerbated by chronic stress exposure. While stress-induced sympathetic activity and elevated glucocorticoid secretion impair cardiovascular health, the mechanisms by which stress-responsive brain regions integrate autonomic and endocrine stress responses remain unclear. This review covers emerging literature on how specific cortical and hypothalamic nuclei regulate cardiovascular and neuroendocrine stress responses. We will also discuss the current understanding of the cellular and circuit mechanisms mediating physiological stress responses. Altogether, the reviewed literature highlights the current state of stress integration research, as well unanswered questions about the brain basis of CVD risk.
Language	English
Publishing date	2022-02-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.820398
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Article: Effects of Biological Sex and Stress Exposure on Ventromedial Prefrontal Regulation of Mood-Related Behaviors.

Wallace, Tyler / Myers, Brent

Frontiers in behavioral neuroscience

2021 Volume 15, Page(s) 737960

Abstract: The ventral portion of the medial prefrontal cortex (vmPFC) regulates mood, sociability, and context-dependent behaviors. Consequently, altered vmPFC activity has been implicated in the biological basis of emotional disorders. Recent methodological ... ...

Abstract	The ventral portion of the medial prefrontal cortex (vmPFC) regulates mood, sociability, and context-dependent behaviors. Consequently, altered vmPFC activity has been implicated in the biological basis of emotional disorders. Recent methodological advances have greatly enhanced the ability to investigate how specific prefrontal cell populations regulate mood-related behaviors, as well as the impact of long-term stress on vmPFC function. However, emerging preclinical data identify prominent sexual divergence in vmPFC behavioral regulation and stress responsivity. Notably, the rodent infralimbic cortex (IL), a vmPFC subregion critical for anti-depressant action, shows marked functional divergence between males and females. Accordingly, this review examines IL encoding and modulation of mood-related behaviors, including coping style, reward, and sociability, with a focus on sex-based outcomes. We also review how these processes are impacted by prolonged stress exposure. Collectively, the data suggest that chronic stress has sex-specific effects on IL excitatory/inhibitory balance that may account for sex differences in the prevalence and course of mood disorders.
Language	English
Publishing date	2021-08-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2021.737960
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Article ; Online: Age and sex disparities in blood pressure control and therapeutic inertia: Impact of a quality improvement program.

Myers, Olivia / Markossian, Talar / Probst, Beatrice / Hiura, Grant / Habicht, Katherine / Egan, Brent / Kramer, Holly

American journal of preventive cardiology

2024 Volume 17, Page(s) 100632

Abstract: Objective: Hypertension quality improvement programs reduce uncontrolled blood pressure (BP) but impact may differ by sex and age.: Methods: This study examined uncontrolled BP, defined as a BP ≥ 140/90 mmHg, and therapeutic inertia, defined as ... ...

Abstract	Objective: Hypertension quality improvement programs reduce uncontrolled blood pressure (BP) but impact may differ by sex and age. Methods: This study examined uncontrolled BP, defined as a BP ≥ 140/90 mmHg, and therapeutic inertia, defined as absence of medication initiation or escalation during visits with uncontrolled BP, by sex and by age group (19-40, 41-65, 66-75, and 76+ years) during a 12 month follow-up period among 21, 861 patients with hypertension and ≥ two visits in primary care clinics enrolled in the American Medical Association (AMA) Results: The mean age was 64.8 years (standard deviation [SD 12.8]) and ranged from 19 to 87 years; 53.6% were female. In age groups 19-40, 41-65, 66-75, 76-87 years, uncontrolled BP at the first clinic visit was present in 51.5%, 42.5%, 37.5% and 36.6% of males, respectively, and in 40.0%, 38.0%, 36.0% and 39.6% of females, respectively. Based on vital signs at the first vs. last clinic visit, the proportion of patients with uncontrolled BP in age groups 19-40, 41-65, 66-75 years declined by 19.4%, 13.5%, 10.1% and 8.7% in males, respectively, and 14.4%, 12.5%, 9.3%, and 8.4%, among females, respectively. Therapeutic inertia ranged from 66.5% and 75.9% of clinic visits among males and females age 19-40 years, to 85.6% and 84.9% of clinic visits among males and females age 76-87 years, respectively. The proportion of clinic visits with therapeutic inertia was lower among males vs. females across all age groups until age 76-87 years. Conclusion: A quality improvement program improves BP control but declines in uncontrolled BP are larger and therapeutic inertia is lower for younger vs. older age groups and for males vs. females. More interventions are needed to reduce sex and age disparities in hypertension management.
Language	English
Publishing date	2024-01-10
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-6677
ISSN (online)	2666-6677
DOI	10.1016/j.ajpc.2023.100632
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Article ; Online: Cortical-brainstem circuitry attenuates physiological stress reactivity.

Pace, Sebastian A / Lukinic, Ema / Wallace, Tyler / McCartney, Carlie / Myers, Brent

The Journal of physiology

2024 Volume 602, Issue 5, Page(s) 949–966

Abstract: Exposure to stressful stimuli promotes multi-system biological responses to restore homeostasis. Catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) facilitate sympathetic activity and promote physiological adaptations, including ... ...

Abstract	Exposure to stressful stimuli promotes multi-system biological responses to restore homeostasis. Catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) facilitate sympathetic activity and promote physiological adaptations, including glycaemic mobilization and corticosterone release. While it is unclear how brain regions involved in the cognitive appraisal of stress regulate RVLM neural activity, recent studies found that the rodent ventromedial prefrontal cortex (vmPFC) mediates stress appraisal and physiological stress responses. Thus, a vmPFC-RVLM connection could represent a circuit mechanism linking stress appraisal and physiological reactivity. The current study investigated a direct vmPFC-RVLM circuit utilizing genetically encoded anterograde and retrograde tract tracers. Together, these studies found that stress-activated vmPFC neurons project to catecholaminergic neurons throughout the ventrolateral medulla in male and female rats. Next, we utilized optogenetic terminal stimulation to evoke vmPFC synaptic glutamate release in the RVLM. Photostimulating the vmPFC-RVLM circuit during restraint stress suppressed glycaemic stress responses in males, without altering the female response. However, circuit stimulation decreased corticosterone responses to stress in both sexes. Circuit stimulation did not modulate affective behaviour in either sex. Further analysis indicated that circuit stimulation preferentially activated non-catecholaminergic medullary neurons in both sexes. Additionally, vmPFC terminals targeted medullary inhibitory neurons. Thus, both male and female rats have a direct vmPFC projection to the RVLM that reduces endocrine stress responses, likely by recruiting local RVLM inhibitory neurons. Ultimately, the excitatory/inhibitory balance of vmPFC synapses in the RVLM may regulate stress reactivity and stress-related health outcomes. KEY POINTS: Glutamatergic efferents from the ventromedial prefrontal cortex target catecholaminergic neurons throughout the ventrolateral medulla. Partially segregated, stress-activated ventromedial prefrontal cortex populations innervate the rostral and caudal ventrolateral medulla. Stimulating ventromedial prefrontal cortex synapses in the rostral ventrolateral medulla decreases stress-induced glucocorticoid release in males and females. Stimulating ventromedial prefrontal cortex terminals in the rostral ventrolateral medulla preferentially activates non-catecholaminergic neurons. Ventromedial prefrontal cortex terminals target medullary inhibitory neurons.
MeSH term(s)	Rats ; Male ; Female ; Animals ; Rats, Sprague-Dawley ; Corticosterone ; Medulla Oblongata/physiology ; Neurons/physiology ; Stress, Physiological
Chemical Substances	Corticosterone (W980KJ009P)
Language	English
Publishing date	2024-02-14
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP285627
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Article: Sex-Specific Cardiac Remodeling in Aged Rats after Early-Life Chronic Stress: Associations with Endocrine and Metabolic Factors.

Dearing, Carley / Sanford, Ella / Olmstead, Nicolette / Morano, Rachel / Wulsin, Lawson / Myers, Brent

bioRxiv : the preprint server for biology

2024

Abstract: Background: Cardiovascular disease is a leading cause of death worldwide. Rates of cardiovascular disease vary both across the lifespan and between sexes. While multiple factors, including adverse life experiences, impact the development and progression ...

Abstract	Background: Cardiovascular disease is a leading cause of death worldwide. Rates of cardiovascular disease vary both across the lifespan and between sexes. While multiple factors, including adverse life experiences, impact the development and progression of cardiovascular disease, the potential interactions of biological sex and stress history on the aged heart are unknown. To this end, we examined sex- and stress-specific impacts on left ventricular hypertrophy (VH) after aging. We hypothesized that early life chronic stress exposure impacts behavioral and physiologic responses that predict cardiac remodeling in a sex-specific manner. Methods: Histological analysis was conducted on hearts of male and female rats previously exposed to chronic variable stress during the late adolescent period (postnatal days 43-62). These animals were challenged with a forced swim test and a glucose tolerance test before aging to 15 months and again being challenged. Predictive analyses were then used to isolate factors that relate to cardiac remodeling among these groups. Results: Early-life chronic stress impacted cardiac remodeling in a sex-specific manner. Among rats with a history of chronic stress, females had increased inward VH. However, there were few associations within the female groups among individual behavioral and physiologic parameters and cardiac remodeling. While males as a group did not have VH after chronic stress, they exhibited multiple individual associations with cardiac susceptibility. Passive coping in young males and active coping in aged males related to VH in a stress history-dependent manner. Moreover, baseline corticosterone positively correlated with VH in unstressed males, while chronically-stressed males had positive correlations between VH and visceral adiposity. Conclusions: These results indicate that females as a group are uniquely susceptible to the effects of early-life stress on cardiac remodeling later in life. Conversely, males have more individual differences in vulnerability, where susceptibility to cardiac remodeling relates to endocrine, metabolic, and behavioral measures depending on stress history. These results ultimately support a framework for accessing cardiovascular risk based on biological sex and prior adverse experiences.
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.03.587944
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Article ; Online: Corticolimbic regulation of cardiovascular responses to stress.

Myers, Brent

Physiology & behavior

2016 Volume 172, Page(s) 49–59

Abstract: Cardiovascular disease, a leading cause of death worldwide, is frequently initiated or exacerbated by stress. In fact, chronic stress exposure and heightened reactions to acute psychological stress are both associated with increased cardiovascular ... ...

Abstract	Cardiovascular disease, a leading cause of death worldwide, is frequently initiated or exacerbated by stress. In fact, chronic stress exposure and heightened reactions to acute psychological stress are both associated with increased cardiovascular morbidity. This brief review focuses on the mechanisms by which corticolimbic nuclei, critical for stress appraisal and emotional reactivity, regulate heart rate and blood pressure responses to psychological stress. Both human and rodent data are examined with a major emphasis on basic studies investigating prefrontal cortex, amygdala, and hippocampus. A detailed literature review reveals substantial limitations in our understanding of this circuitry, as well as significant opportunities for future investigation that may ultimately reduce the burden of cardiovascular illness.
MeSH term(s)	Amygdala/physiology ; Animals ; Cardiovascular System/physiopathology ; Hippocampus/physiology ; Humans ; Neural Pathways/physiopathology ; Prefrontal Cortex/physiology ; Stress, Psychological/physiopathology
Language	English
Publishing date	2016-10-25
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2016.10.015
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Article ; Online: Sex differences in autonomic responses to stress: implications for cardiometabolic physiology.

Dearing, Carley / Handa, Robert J / Myers, Brent

American journal of physiology. Endocrinology and metabolism

2022 Volume 323, Issue 3, Page(s) E281–E289

Abstract: Chronic stress is a significant risk factor for negative health outcomes. Furthermore, imbalance of autonomic nervous system control leads to dysregulation of physiological responses to stress and contributes to the pathogenesis of cardiometabolic and ... ...

Abstract	Chronic stress is a significant risk factor for negative health outcomes. Furthermore, imbalance of autonomic nervous system control leads to dysregulation of physiological responses to stress and contributes to the pathogenesis of cardiometabolic and psychiatric disorders. However, research on autonomic stress responses has historically focused on males, despite evidence that females are disproportionality affected by stress-related disorders. Accordingly, this mini-review focuses on the influence of biological sex on autonomic responses to stress in humans and rodent models. The reviewed literature points to sex differences in the consequences of chronic stress, including cardiovascular and metabolic disease. We also explore basic rodent studies of sex-specific autonomic responses to stress with a focus on sex hormones and hypothalamic-pituitary-adrenal axis regulation of cardiovascular and metabolic physiology. Ultimately, emerging evidence of sex differences in autonomic-endocrine integration highlights the importance of sex-specific studies to understand and treat cardiometabolic dysfunction.
MeSH term(s)	Autonomic Nervous System ; Cardiovascular Diseases/metabolism ; Female ; Humans ; Hypothalamo-Hypophyseal System/metabolism ; Male ; Pituitary-Adrenal System/metabolism ; Sex Characteristics ; Stress, Psychological/metabolism
Language	English
Publishing date	2022-07-06
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00058.2022
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Uc I Zs.89: Show issues

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Article ; Online: Evaluation of Coffea arabica Cultivars for Resistance to Meloidogyne konaensis

Roxana Myers / Cathy Mello / Chifumi Nagai / Brent Sipes / Tracie Matsumoto

Agriculture, Vol 13, Iss 1168, p

2023 Volume 1168

Abstract: Coffee is an important agricultural crop for the State of Hawaii. Developing new coffee cultivars with resistance to damaging pests and diseases is crucial for improving production and maintaining the profitability of the industry. With the recent ... ...

Abstract	Coffee is an important agricultural crop for the State of Hawaii. Developing new coffee cultivars with resistance to damaging pests and diseases is crucial for improving production and maintaining the profitability of the industry. With the recent discovery of Hemileia vastatrix , coffee leaf rust (CLR), to Hawaii there is a strong interest in replanting with CLR-resistant germplasm. However, when selecting an appropriate cultivar for replanting, susceptibility to other pathogens, such as plant-parasitic nematodes, should be taken into consideration. Meloidogyne konaensis , the Kona coffee root-knot nematode, causes severe destruction of the root system, reducing the yield and causing the mortality of susceptible Coffea arabica cv. Typica trees. Fortunately, resistance to root-knot nematodes has been found in some C. arabica germplasm. In this study, accessions of wild Ethiopian C. arabica and two CLR-resistant C. arabica cultivars, Tupi-HI and Obata, were evaluated for resistance to M. konaensis in a greenhouse bioassay. All Ethiopian accessions retained high levels of resistance, resulting in reproductive factors (Rfs) lower than 1.0, and low root-rot ratings. Tupi-HI was highly susceptible to M. konanensis , with an Rf value of 7.12, whereas Obata was slightly susceptible, with an Rf value of 2.33. Both cultivars had high root-rot ratings, suggesting intolerance to the nematode. Hybridizing Ethiopian C. arabica with Tupi-HI or Obata may result in new elite cultivars, resistant to both H. vastatrix and M. konaensis .
Keywords	Coffea arabica ; coffee ; host–plant resistance ; Meloidogyne konaensis ; root-knot nematode ; Agriculture (General) ; S1-972
Subject code	580
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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