Eric G Krause

University of Florida, Gainesville, Florida, United States

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Publications (51)186.36 Total impact

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    ABSTRACT: Despite tremendous research efforts, hypertension remains an epidemic health concern, leading often to the development of cardiovascular disease. It is well-established that in many instances, the brain plays an important role in the onset and progression of hypertension via activation of the sympathetic nervous system. Further, the activity of the renin angiotensin system (RAS) and of glial-mediated pro-inflammatory processes have independently been linked to this neural control and are, as a consequence, both attractive targets for the development of anti-hypertensive therapeutics. Although it is clear that the predominant effector peptide of the RAS, angiotensin-II, activates its type-1 receptor on neurons to mediate some of its hypertensive actions, additional nuances of this brain RAS control of blood pressure are constantly being uncovered. One of these complexities is that the RAS is now thought to impact cardiovascular control, in part, via facilitating a glial cell-dependent pro-inflammatory milieu within cardiovascular control centers. Another is that the newly-characterized antihypertensive limbs of the RAS are now recognized to, in many cases, antagonize the pro-hypertensive AT1R-mediated effects. That being said, the mechanism by which the RAS, glia and neurons interact to regulate blood pressure is an active area of ongoing research. Here we review the current understanding of these interactions and present a hypothetical model of how these exchanges may ultimately regulate cardiovascular function. Copyright © 2015, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    AJP Regulatory Integrative and Comparative Physiology 06/2015; DOI:10.1152/ajpregu.00078.2015 · 3.53 Impact Factor
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    ABSTRACT: Glucocorticoids act rapidly at the paraventricular nucleus (PVN) to inhibit stress-excitatory neurons and limit excessive glucocorticoid secretion. The signaling mechanism underlying rapid feedback inhibition remains to be determined The present study was designed to test the hypothesis that the canonical glucocorticoid receptors (GR) is required for appropriate hypothalamic-pituitary-adrenal (HPA) axis regulation. Local PVN GR knockdown was achieved by breeding homozygous floxed GR mice with Sim1-cre recombinase transgenic mice. This genetic approach created mice with a knockdown of GR primarily confined to hypothalamic cell groups including the PVN, sparing GR expression in other HPA axis limbic regulatory regions and the pituitary. There were no differences in circadian nadir and peak corticosterone concentrations between male PVN GR KD mice and male littermate controls. However, reduction of PVN GR increased ACTH and corticosterone responses to acute, but not chronic stress, indicating that PVN GR is critical for limiting neuroendocrine responses to acute stress in males. Loss of PVN GR induced an opposite neuroendocrine phenotype in females, characterized by increased circadian nadir corticosterone levels and suppressed ACTH responses to acute restraint stress, without a concomitant change in corticosterone responses under acute or chronic stress conditions. PVN GR deletion had no effect on depression-like behavior in either sex in the forced swim test. Overall, these findings reveal pronounced sex differences in the PVN GR dependence of acute stress feedback regulation of HPA axis function. In addition, these data further indicate that glucocorticoid control of HPA axis responses following chronic stress operates via a PVN-independent mechanism.
    Endocrinology 06/2015; DOI:10.1210/en.2015-1276 · 4.64 Impact Factor
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    ABSTRACT: Challenges to body fluid homeostasis can have a profound impact on hypothalamic regulation of stress responsiveness. Deficiencies in blood volume or sodium concentration leads to the generation of neural and humoral signals relayed through the hindbrain and circumventricular organs that apprise the paraventricular nucleus of the hypothalamus (PVH) of hydromineral imbalance. Collectively, these neural and humoral signals converge onto PVH neurons, including those that express corticotrophin-releasing factor (CRF), oxytocin (OT), and vasopressin, to influence their activity and initiate compensatory responses that alleviate hydromineral imbalance. Interestingly, following exposure to perceived threats to homeostasis, select limbic brain regions mediate behavioral and physiological responses to psychogenic stressors, in part, by influencing activation of the same PVH neurons that are known to maintain body fluid homeostasis. Here, we review past and present research examining interactions between hypothalamic circuits regulating body fluid homeostasis and those mediating behavioral and physiological responses to psychogenic stress.
    Frontiers in Systems Neuroscience 03/2015; 9:46. DOI:10.3389/fnsys.2015.00046
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    ABSTRACT: Stress-related (e.g., depression) and metabolic pathologies (e.g., obesity) are important and often co-morbid public health concerns. Here we identify a connection between peripheral glucocorticoid receptor (GR) signaling originating in fat with the brain control of both stress and metabolism. Mice with reduced adipocyte GR hypersecrete glucocorticoids following acute psychogenic stress and are resistant to diet-induced obesity. This hypersecretion gives rise to deficits in responsiveness to exogenous glucocorticoids, consistent with reduced negative feedback via adipocytes. Increased stress reactivity occurs in the context of elevated hypothalamic expression of hypothalamic-pituitary-adrenal (HPA) axis-excitatory neuropeptides and in the absence of altered adrenal sensitivity, consistent with a central cite of action. Our results identify a novel mechanism whereby activation of the adipocyte GR promotes peripheral energy storage while inhibiting the HPA axis, and provide functional evidence for a fat-to-brain regulatory feedback network that serves to regulate not just homeostatic energy balance but also responses to psychogenic stimuli. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Psychoneuroendocrinology 03/2015; 56. DOI:10.1016/j.psyneuen.2015.03.008 · 5.59 Impact Factor
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    ABSTRACT: In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral. However, stimulation of AT2R locally within the brain or the kidney apparently elicits a systemic blood pressure lowering effect. A systemic effect of AT2R stimulation on blood pressure can also be achieved, when the prevailing effect of continuous background AT1R-stimulation is attenuated by low-dose AT1R blockade. Despite a lack of effect on blood pressure, AT2R stimulation still protects from hypertensive end-organ damage. Current data and evidence therefore suggest that AT2R agonists will not be suitable as future anti-hypertensive drugs, but that they may well be useful for end-organ protection in combination with established anti-hypertensives. Copyright © 2015. Published by Elsevier Ltd.
    Current Opinion in Pharmacology 02/2015; 21C:115-121. DOI:10.1016/j.coph.2015.01.004 · 4.23 Impact Factor
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    ABSTRACT: Angiotensin-II acts at its type-1 receptor (AT1R) in the brain to regulate body fluid homeostasis, sympathetic outflow and blood pressure. However, the role of the angiotensin type-2 receptor (AT2R) in the neural control of these processes has received far less attention, largely because of limited ability to effectively localize these receptors at a cellular level in the brain. The present studies combine the use of a bacterial artificial chromosome transgenic AT2R-enhanced green fluorescent protein (eGFP) reporter mouse with recent advances in in situ hybridization (ISH) to circumvent this obstacle. Dual immunohistochemistry (IHC)/ISH studies conducted in AT2R-eGFP reporter mice found that eGFP and AT2R mRNA were highly co-localized within the brain. Qualitative analysis of eGFP immunoreactivity in the brain then revealed localization to neurons within nuclei that regulate blood pressure, metabolism, and fluid balance (e.g., NTS and median preoptic nucleus [MnPO]), as well as limbic and cortical areas known to impact stress responding and mood. Subsequently, dual IHC/ISH studies uncovered the phenotype of specific populations of AT2R-eGFP cells. For example, within the NTS, AT2R-eGFP neurons primarily express glutamic acid decarboxylase-1 (80.3 ± 2.8 %), while a smaller subset express vesicular glutamate transporter-2 (18.2 ± 2.9 %) or AT1R (8.7 ± 1.0 %). No co-localization was observed with tyrosine hydroxylase in the NTS. Although AT2R-eGFP neurons were not observed within the paraventricular nucleus (PVN) of the hypothalamus, eGFP immunoreactivity is localized to efferents terminating in the PVN and within GABAergic neurons surrounding this nucleus. These studies demonstrate that central AT2R are positioned to regulate blood pressure, metabolism, and stress responses.
    Brain Structure and Function 11/2014; DOI:10.1007/s00429-014-0943-1 · 4.57 Impact Factor
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    ABSTRACT: Previous investigation by our laboratory found that acute hypernatremia potentiates an oxytocinergic tone that inhibits parvocellular neurosecretory neurons in the paraventricular nucleus of the hypothalamus (PVN), attenuates restraint-induced surges in corticosterone (CORT), and reduces anxiety-like behavior in male rats. To investigate the neural mechanisms mediating these effects and extend our findings to a more versatile species, we repeated our studies using laboratory mice. In response to 2.0M NaCl injections, mice had increased plasma sodium concentrations which were associated with a blunted rise in CORT subsequent to restraint challenge relative to 0.15M NaCl injected controls. Immunofluorescent identification of the immediate early gene product Fos found that 2.0M NaCl treatment increased the number of activated neurons producing oxytocin in the PVN. To evaluate the effect of acute hypernatremia on PVN neurons producing corticotropin-releasing hormone (CRH), we used the Cre-lox system to generate mice that produced the red fluorescent protein, tdTomato, in cells that had Cre-recombinase activity driven by CRH gene expression. Analysis of brain tissue from these CRH-reporter mice revealed 2.0M NaCl treatment caused a dramatic reduction in Fos-positive nuclei specifically in CRH-producing PVN neurons. This altered pattern of activity was predictive of alleviated anxiety-like behavior as mice administered 2.0M NaCl spent more time exploring the open arms of an elevated-plus maze than 0.15M NaCl treated controls. Taken together, these results further implicate an oxytocin-dependent inhibition of CRH neurons in the PVN and demonstrate the impact that slight elevations in plasma sodium have on hypothalamic-pituitary-adrenocortical axis output and anxiety-like behavior.
    Physiology & Behavior 04/2014; 136. DOI:10.1016/j.physbeh.2014.03.027 · 3.03 Impact Factor
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    ABSTRACT: Chronic variable stress (CVS) exposure modifies the paraventricular nucleus of the hypothalamus (PVN) in a manner consistent with enhanced central drive of the hypothalamo-pituitary-adrenocortical (HPA) axis. As previous reports suggest that post-stress enhancement of norepinephrine (NE) action contributes to chronic stress regulation at the level of the PVN, we hypothesised that PVN-projecting NE neurons were necessary for the stress facilitatory effects of CVS. Following intra-PVN injection of saporin toxin conjugated to a dopamine beta-hydroxylase (DBH) antibody (DSAP), in rats PVN DBH immunoreactivity was almost completely eliminated, but immunoreactive afferents to other key regions involved in stress integration were spared (e.g. DBH fiber densities were unaffected in the central nucleus of the amygdala). Reductions in DBH-positive fiber density were associated with reduced numbers of DBH-immunoreactive neurons in the nucleus of the solitary tract and locus coeruleus. Following 2 weeks of CVS, DSAP injection did not alter stress-induced adrenal hypertrophy or attenuation of body weight gain, indicating that PVN-projecting NE [and epinephrine (E)] neurons are not essential for these physiological effects of chronic stress. In response to acute restraint stress, PVN-targeted DSAP injection attenuated peak adrenocorticotrophic hormone (ACTH) and corticosterone in controls, but only attenuated peak ACTH in CVS animals, suggesting that enhanced adrenal sensitivity compensated for reduced excitatory drive of the PVN. Our data suggest that PVN-projecting NE/E neurons contribute to the generation of acute stress responses, and are required for HPA axis drive (ACTH release) during chronic stress. However, loss of NE/E drive at the PVN appears to be buffered by compensation at the level of the adrenal.
    European Journal of Neuroscience 04/2014; 39(11). DOI:10.1111/ejn.12587 · 3.67 Impact Factor
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    ABSTRACT: Valvular disease is common in patients with Marfan syndrome and can lead to cardiomyopathy. However, some patients develop cardiomyopathy in the absence of hemodynamically significant valve dysfunction, suggesting alternative mechanisms of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1) in smooth muscle cells has been shown to cause vascular pathologies similar to Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and aortic aneurysms. This study used echocardiography and blood pressure monitoring in mouse models to determine whether inactivation of Lrp1 in vascular smooth muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence of valvular disease. Hemodynamic changes during treatment with captopril were also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice and progressed as they aged, whereas no significant aortic dilation was detected in wild type littermates. Diastolic blood pressure was lower and pulse pressure higher in Lrp1-knockout mice, which was normalized by treatment with captopril. Aortic dilation was followed by development of aortic insufficiency and subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle cell Lrp1 deficiency results in aortic dilation and insufficiency that causes secondary cardiomyopathy that can be improved by captopril. These findings provide novel insights into mechanisms of cardiomyopathy associated with vascular activation and offer a new model of valvular cardiomyopathy.
    PLoS ONE 11/2013; 8(11):e82026. DOI:10.1371/journal.pone.0082026 · 3.53 Impact Factor
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    ABSTRACT: High salt diet can reduce anxiety-like behavior and, yet can also promote hypertension. Previous work from our lab has shown that mild transient increase in plasma sodium and osmolality can elevate the central levels of oxytocin which can then act on pathways that mediate stress responsiveness and anxiety-like behavior. Here, we used CRF reporter mice to discern the central oxytocinergic pathways associated with heightened stress responsiveness. For all the experiments, animals were rendered osmotically dehydrated and testing was conducted 1 hour after the injections to ensure elevated central levels of oxytocin. The degree of hypernatremia was assessed by measuring plasma sodium concentration (pNa+) and osmolality (pOsm) following injections of either 2.0 M NaCl or 0.15 M NaCl. Restraint was used as a psychogenic stressor to determine the effect of hypernatremia on the plasma corticosterone levels as well as patterns of neuronal activation. Anxiety-like behavior was studied using the elevated-plus-maze after administration of either 2 M NaCl or 0.15 M NaCl. For electrophysiological studies, 1 hour after injecting the animals, brain slices were prepared containing the paraventricular nucleus of the hypothalamus and recordings were made from Type I and Type II parvocellular neurons. The Cre/lox system was used to generate CRF reporter mice to identify CRF neurons.
    SFN 2013, San Diego; 11/2013
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    ABSTRACT: Anxiety disorders are the most common psychiatric illness and are associated with heightened stress responsiveness. The neuropeptide oxytocin (OT) has garnered significant attention for its potential as a treatment for anxiety disorders; however, the mechanism mediating its effects on stress-responding and anxiety is not well-understood. Here we use acute hypernatremia, a stimulus that elevates brain levels of OT, to discern the central oxytocinergic pathways mediating stress responsiveness and anxiety-like behavior. Rats were rendered hypernatremic by acute administration of 2.0 M NaCl and had increased plasma sodium concentration, plasma osmolality and Fos induction in OT-containing neurons relative to 0.15 M NaCl treated controls. Acute hypernatremia decreased restraint-induced elevations in corticosterone (CORT) and created an inhibitory oxytocinergic tone on parvocellular neurosecretory neurons within the paraventricular nucleus of the hypothalamus. In contrast, evaluation of Fos immunohistochemistry determined that acute hypernatremia followed by restraint increased neuronal activation in brain regions receiving OT afferents that are also implicated in the expression of anxiety-like behavior. To determine whether these effects were predictive of altered anxiety-like behavior, rats were subjected to acute hypernatremia and then tested in the elevated plus maze (EPM). Relative to controls given 0.15 M NaCl, rats given 2.0 M NaCl spent more time in the open arms of the EPM, suggesting that acute hypernatremia is anxiolytic. Collectively, the results suggest that acute elevations in the pNa(+) increase central levels of OT, which decreases anxiety by altering neuronal activity in hypothalamic and limbic nuclei.
    Endocrinology 05/2013; 154(7). DOI:10.1210/en.2013-1049 · 4.64 Impact Factor
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    ABSTRACT: Obesity is associated with increased levels of angiotensin-II (Ang-II), which activates angiotensin type 1a receptors (AT1a) to influence cardiovascular function and energy homeostasis. To test the hypothesis that specific AT1a within the brain control these processes, we used the Cre/lox system to delete AT1a from the paraventricular nucleus of the hypothalamus (PVN) of mice. PVN AT1a deletion did not affect body mass or adiposity when mice were maintained on standard chow. However, maintenance on a high-fat diet revealed a gene by environment interaction whereby mice lacking AT1a in the PVN had increased food intake and decreased energy expenditure that augmented body mass and adiposity relative to controls. Despite this increased adiposity, PVN AT1a deletion reduced systolic blood pressure, suggesting that this receptor population mediates the positive correlation between adiposity and blood pressure. Gene expression studies revealed that PVN AT1a deletion decreased hypothalamic expression of corticotrophin-releasing hormone and oxytocin, neuropeptides known to control food intake and sympathetic nervous system activity. Whole-cell patch-clamp recordings confirmed that PVN AT1a deletion eliminates responsiveness of PVN parvocellular neurons to Ang-II, and suggest that Ang-II responsiveness is increased in obese wild-type mice. Central inflammation is associated with metabolic and cardiovascular disorders and PVN AT1a deletion reduced indices of hypothalamic inflammation. Collectively, these studies demonstrate that PVN AT1a regulate energy balance during environmental challenges that promote metabolic and cardiovascular pathologies. The implication is that the elevated Ang-II that accompanies obesity serves as a negative feedback signal that activates PVN neurons to alleviate weight gain.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 03/2013; 33(11):4825-33. DOI:10.1523/JNEUROSCI.3806-12.2013 · 6.75 Impact Factor
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    ABSTRACT: Hypertension is an epidemic health concern and a major risk factor for the development of cardiovascular disease. Although there are available treatment strategies for hypertension, numerous hypertensive patients do not have their clinical symptoms under control and it is imperative that new avenues to treat or prevent high blood pressure in these patients are developed. It is well established that increases in sympathetic nervous system (SNS) outflow and enhanced renin-angiotensin system (RAS) activity are common features of hypertension and various pathological conditions that predispose individuals to hypertension. More recently, hypertension has also become recognized as an immune condition and accumulating evidence suggests that interactions between the RAS, SNS and immune systems play a role in blood pressure regulation. This review summarizes what is known about the interconnections between the RAS, SNS and immune systems in the neural regulation of blood pressure. Based on the reviewed studies, a model for RAS/neuroimmune interactions during hypertension is proposed and the therapeutic potential of targeting RAS/neuroimmune interactions in hypertensive patients is discussed. Special emphasis is placed on the applicability of the proposed model to obesity-related hypertension.
    Pharmacology [?] Therapeutics 02/2013; 138(3). DOI:10.1016/j.pharmthera.2013.02.005 · 7.75 Impact Factor
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    ABSTRACT: During recovery from social stress in a visible burrow system (VBS), during which a dominance hierarchy is formed among the males, rats display hyperphagia and gain weight preferentially as visceral adipose tissue. By proportionally increasing visceral adiposity, social stress may contribute to the establishment of metabolic disorder. Amylin was administered to rats fed ad libitum during recovery from VBS stress in an attempt to prevent hyperphagia and the resultant gain in body weight and fat mass. Amylin treatment reduced food intake, weight gain, and accumulation of fat mass in male burrow rats, but not in male controls that spent time housed with a single female rather than in the VBS. Amylin did not alter neuropeptide Y (NPY), agouti-related peptide (AgRP), or proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus of the hypothalamus as measured at the end of the recovery period, nor did it affect plasma corticosterone or leptin. Amylin exerted most of its effect on food intake during the first few days of recovery, possibly through antagonism of NPY and/or increasing leptin sensitivity. The potential for chronic social stress to contribute to metabolic disorder is diminished by amylin treatment, though the neuroendocrine mechanisms behind this effect remain elusive.
    AJP Regulatory Integrative and Comparative Physiology 07/2012; 303(6):R676-82. DOI:10.1152/ajpregu.00090.2012 · 3.53 Impact Factor
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    ABSTRACT: Chronic stress induces presynaptic and postsynaptic modifications in the paraventricular nucleus of the hypothalamus that are consistent with enhanced excitatory hypothalamo-pituitary-adrenocortical (HPA) axis drive. The brain regions mediating these molecular modifications are not known. We hypothesized that chronic variable stress (CVS) tonically activates stress-excitatory regions that interact with the paraventricular nucleus of the hypothalamus, culminating in stress facilitation. In order to identify chronically activated brain regions, ΔFosB, a documented marker of tonic neuronal activation, was assessed in known stress regulatory limbic and brainstem sites. Four experimental groups were included: CVS, repeated restraint (RR) (control for HPA habituation), animals weight-matched (WM) to CVS animals (control for changes in circulating metabolic factors due to reduced weight gain), and non-handled controls. CVS, (but not RR or WM) induced adrenal hypertrophy, indicating that sustained HPA axis drive only occurred in the CVS group. CVS (but not RR or WM) selectively increased the number of FosB/ΔFosB nuclei in the nucleus of the solitary tract, posterior hypothalamic nucleus, and both the infralimbic and prelimbic divisions of the medial prefrontal cortex, indicating an involvement of these regions in chronic drive of the HPA axis. Increases in FosB/ΔFosB-immunoreactive cells were observed following both RR and CVS in the other regions (e.g. the dorsomedial hypothalamus), suggesting activation by both habituating and non-habituating stress conditions. The data suggest that unpredictable stress uniquely activates interconnected cortical, hypothalamic, and brainstem nuclei, potentially revealing the existence of a recruited circuitry mediating chronic drive of brain stress effector systems.
    European Journal of Neuroscience 07/2012; 36(4):2547-55. DOI:10.1111/j.1460-9568.2012.08161.x · 3.67 Impact Factor
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    ABSTRACT: This study elucidates the neural circuits by which circulating angiotensin II (ANGII) acts in the brain to influence humoral and behavioral responses to psychological stressors. To test the hypothesis that systemic ANGII mediates stress responding via the subfornical organ (SFO), we first found that the timing of increased systemic ANGII in response to 60 min restraint coincides with increased c-fos mRNA expression in the SFO. Next, we administered an anterograde neuronal tract tracer into the SFO and found that fibers originating there make appositions onto neurons in the paraventricular nucleus of the hypothalamus that are also c-fos positive following restraint stress. To determine whether circulating ANGII stimulates the release of stress hormones via activation of angiotensin type 1 receptors (AT1R) within the SFO, we delivered lentivirus to knockdown AT1R expression locally in the SFO. Inhibition of AT1R specifically within the SFO blunted the release of adrenocorticotrophin-releasing hormone and corticosterone in response to restraint stress and caused rats to spend more time in the open arms of an elevated-plus maze than controls, indicating that inhibition of AT1R within the SFO is anxiolytic. Collectively, these results suggest that circulating ANGII acts on AT1R in the SFO to influence responding to psychological stressors.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/2011; 31(42):15009-15. DOI:10.1523/JNEUROSCI.0892-11.2011 · 6.75 Impact Factor
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    ABSTRACT: Considerable evidence implicates the renin-angiotensin system (RAS) in the regulation of energy balance. To evaluate the role of the RAS in the central nervous system regulation of energy balance, we used osmotic minipumps to chronically administer angiotensin II (Ang II; icv; 0.7 ng/min for 24 days) to adult male Long-Evans rats, resulting in reduced food intake, body weight gain, and adiposity. The decrease in body weight and adiposity occurred relative to both ad libitum- and pair-fed controls, implying that reduced food intake in and of itself does not underlie all of these effects. Consistent with this, rats administered Ang II had increased whole body heat production and oxygen consumption. Additionally, chronic icv Ang II increased uncoupling protein-1 and β(3)-adrenergic receptor expression in brown adipose tissue and β3-adrenergic receptor expression in white adipose tissue, which is suggestive of enhanced sympathetic activation and thermogenesis. Chronic icv Ang II also increased hypothalamic agouti-related peptide and decreased hypothalamic proopiomelanocortin expression, consistent with a state of energy deficit. Moreover, chronic icv Ang II increased the anorectic corticotrophin- and thyroid-releasing hormones within the hypothalamus. These results suggest that Ang II acts in the brain to promote negative energy balance and that contributing mechanisms include an alteration in the hypothalamic circuits regulating energy balance, a decrease in food intake, an increase in energy expenditure, and an increase in sympathetic activation of brown and white adipose tissue.
    AJP Endocrinology and Metabolism 08/2011; 301(6):E1081-91. DOI:10.1152/ajpendo.00307.2011 · 4.09 Impact Factor
  • Appetite 07/2011; 57. DOI:10.1016/j.appet.2011.05.155 · 2.69 Impact Factor
  • Appetite 07/2011; 57:S24. DOI:10.1016/j.appet.2011.05.202 · 2.69 Impact Factor
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    ABSTRACT: Life stress frequently occurs within the context of homeostatic challenge, requiring integration of physiological and psychological need into appropriate hormonal, cardiovascular, and behavioral responses. To test neural mechanisms underlying stress integration within the context of homeostatic adversity, we evaluated the impact of a pronounced physiological (hypernatremia) challenge on hypothalamic-pituitary-adrenal (HPA), cardiovascular, and behavioral responses to an acute psychogenic stress. Relative to normonatremic controls, rats rendered mildly hypernatremic had decreased HPA activation in response to physical restraint, a commonly used rodent model of psychogenic stress. In addition, acute hypernatremia attenuated the cardiovascular response to restraint and promoted faster recovery to prestress levels. Subsequent to restraint, hypernatremic rats had significantly more c-Fos expression in oxytocin- and vasopressin-containing neurons within the supraoptic and paraventricular nuclei of the hypothalamus. Hypernatremia also completely eliminated the increased plasma renin activity that accompanied restraint in controls, but greatly elevated circulating levels of oxytocin. The endocrine and cardiovascular profile of hypernatremic rats was predictive of decreased anxiety-like behavior in the social interaction test. Collectively, the results indicate that acute hypernatremia is a potent inhibitor of the HPA, cardiovascular, and behavioral limbs of the stress response. The implications are that the compensatory responses that promote renal-sodium excretion when faced with hypernatremia also act on the nervous system to decrease reactivity to psychogenic stressors and facilitate social behavior, which may suppress the anxiety associated with approaching a communal water source and support the social interactions that may be encountered when engaging in drinking behavior.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 04/2011; 31(14):5470-6. DOI:10.1523/JNEUROSCI.6078-10.2011 · 6.75 Impact Factor

Publication Stats

565 Citations
186.36 Total Impact Points

Institutions

  • 2011–2015
    • University of Florida
      • Department of Pharmacodynamics
      Gainesville, Florida, United States
  • 2007–2014
    • University of Cincinnati
      • Department of Psychiatry
      Cincinnati, Ohio, United States
  • 2001–2007
    • Florida State University
      • • Department of Psychology
      • • Program in Neuroscience
      Tallahassee, Florida, United States