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Roger A. L. Dampney - One of the best experts on this subject based on the ideXlab platform.

  • Cardiovascular Responses Evoked by Leptin Acting on Neurons in the Ventromedial and
    2016
    Co-Authors: Dorsomedial Hypothalamus, Suzanne Killinger, Jaimie W. Polson, Ainsley J. Marsh, Dorota B. Pawlak, Marco A. P. Fontes, Roger A. L. Dampney
    Abstract:

    Abstract—Leptin, a circulating hormone produced by adipose tissue, is believed to act on the hypothalamus to increase sympathetic vasomotor activity, in addition to its well-known effects on appetite and energy expenditure. In this study, we determined the cardiovascular effects of direct application of leptin to specific cell groups within the hypothalamus that are known to be activated by circulating leptin. In rats anesthetized with urethane, microinjections of leptin (16 ng in 20 nL solution) were made into the ventromedial Hypothalamic Nucleus, Dorsomedial Hypothalamic Nucleus, and paraventricular Nucleus. Compared with vehicle solution, microinjections of leptin into the ventromedial Hypothalamic Nucleus evoked significant increases in arterial pressure and renal sympathetic nerve activity, but not heart rate. In contrast, microinjections of leptin into the Dorsomedial Hypothalamic Nucleus evoked significant increases in arterial pressure and heart rate but not renal sympathetic nerve activity, whereas microinjections of leptin into the paraventricular Nucleus had no significant effect on any of the measured cardiovascular variables. These results indicate that the ventromedial and Dorsomedial Hypothalamic regions might be important sites at which leptin activation leads to increases in sympathetic vasomotor activity and heart rate, as occurs in obesity-related hypertension. (Hypertension. 2003;42:488-493.) Key Words: hypothalamus sympathetic nervous system arterial pressure heart rate brain hypertension, experimental obesit

  • Modulation of the baroreceptor reflex by the Dorsomedial Hypothalamic Nucleus and perifornical area
    American journal of physiology. Regulatory integrative and comparative physiology, 2005
    Co-Authors: Lachlan M. Mcdowall, Jouji Horiuchi, Suzanne Killinger, Roger A. L. Dampney
    Abstract:

    Neurons within the Dorsomedial Hypothalamic Nucleus (DMH) and perifornical area (PeF), which lie within the classic Hypothalamic defense area, subserve the cardiovascular response to psychological ...

  • Activation of 5-Hydroxytryptamine 1A Receptors Suppresses the Cardiovascular Response Evoked From the Dorsomedial Hypothalamic Nucleus
    Hypertension (Dallas Tex. : 1979), 2005
    Co-Authors: Jouji Horiuchi, Sonoe Wakabayashi, Roger A. L. Dampney
    Abstract:

    The Dorsomedial Hypothalamic Nucleus is a key component of the central pathways subserving the cardiovascular response to psychological stress, which is believed to be an important risk factor for hypertension. Previous studies indicate that 5-hydroxytryptamine 1A receptors can modulate the cardiovascular responses associated with stress. In this study, we determined in anesthetized rats the effects of systemic or intracisternal administration of 8-hydroxy-2-(di-n-propylamino)tetralin, a selective agonist of 5-hydroxytryptamine 1A receptors, and then subsequent administration of the selective antagonist WAY-100635 on the cardiovascular response evoked by activation of the Dorsomedial Hypothalamic Nucleus (by microinjection of bicuculline). The increase in mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) evoked by bicuculline injection into the Dorsomedial Hypothalamic Nucleus was greatly reduced (by 80% to 90%) by administration of 8-hydroxy-2-(di-n-propylamino)tetralin and then completely restored by subsequent administration of WAY-100635, whether administered systemically or intracisternally. In contrast, systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin had no significant effect on the baseline level or reflex changes in RSNA evoked by chemoreceptor or baroreceptor stimulation and resulted in only a modest reduction (12 mm Hg) in baseline mean arterial pressure. The results indicate that activation of 5-hydroxytryptamine 1A receptors in the brain stem causes a potent and selective suppression of the hypertensive and sympathoexcitatory response evoked by stimulation of the Dorsomedial Hypothalamic Nucleus but has little effect on the tonic level or baroreceptor or chemoreceptor reflex control of RSNA.

  • Descending vasomotor pathways from the Dorsomedial Hypothalamic Nucleus: role of medullary raphe and RVLM
    American journal of physiology. Regulatory integrative and comparative physiology, 2004
    Co-Authors: Jouji Horiuchi, Suzanne Killinger, Robin M. Mcallen, Andrew M. Allen, Marco Antônio Peliky Fontes, Roger A. L. Dampney
    Abstract:

    The Dorsomedial Hypothalamic Nucleus (DMH) is believed to play a key role in mediating vasomotor and cardiac responses evoked by an acute stress. Inhibition of neurons in the rostral ventrolateral ...

  • Cardiovascular Responses Evoked by Leptin Acting on Neurons in the Ventromedial and Dorsomedial Hypothalamus
    Hypertension (Dallas Tex. : 1979), 2003
    Co-Authors: Ainsley J. Marsh, Suzanne Killinger, Marco Antônio Peliky Fontes, Jaimie W. Polson, Dorota B. Pawlak, Roger A. L. Dampney
    Abstract:

    Leptin, a circulating hormone produced by adipose tissue, is believed to act on the hypothalamus to increase sympathetic vasomotor activity, in addition to its well-known effects on appetite and energy expenditure. In this study, we determined the cardiovascular effects of direct application of leptin to specific cell groups within the hypothalamus that are known to be activated by circulating leptin. In rats anesthetized with urethane, microinjections of leptin (16 ng in 20 nL solution) were made into the ventromedial Hypothalamic Nucleus, Dorsomedial Hypothalamic Nucleus, and paraventricular Nucleus. Compared with vehicle solution, microinjections of leptin into the ventromedial Hypothalamic Nucleus evoked significant increases in arterial pressure and renal sympathetic nerve activity, but not heart rate. In contrast, microinjections of leptin into the Dorsomedial Hypothalamic Nucleus evoked significant increases in arterial pressure and heart rate but not renal sympathetic nerve activity, whereas microinjections of leptin into the paraventricular Nucleus had no significant effect on any of the measured cardiovascular variables. These results indicate that the ventromedial and Dorsomedial Hypothalamic regions might be important sites at which leptin activation leads to increases in sympathetic vasomotor activity and heart rate, as occurs in obesity-related hypertension.

Clifford B. Saper - One of the best experts on this subject based on the ideXlab platform.

  • differential rescue of light and food entrainable circadian rhythms
    Science, 2008
    Co-Authors: Patrick M Fuller, Clifford B. Saper
    Abstract:

    When food is plentiful, circadian rhythms of animals are powerfully entrained by the light-dark cycle. However, if animals have access to food only during their normal sleep cycle, they will shift most of their circadian rhythms to match the food availability. We studied the basis for entrainment of circadian rhythms by food and light in mice with targeted disruption of the clock gene Bmal1, which lack circadian rhythmicity. Injection of a viral vector containing the Bmal1 gene into the suprachiasmatic nuclei of the hypothalamus restored light-entrainable, but not food-entrainable, circadian rhythms. In contrast, restoration of the Bmal1 gene only in the Dorsomedial Hypothalamic Nucleus restored the ability of animals to entrain to food but not to light. These results demonstrate that the Dorsomedial hypothalamus contains a Bmal1-based oscillator that can drive food entrainment of circadian rhythms.

  • the Dorsomedial Hypothalamic Nucleus is critical for the expression of food entrainable circadian rhythms
    Nature Neuroscience, 2006
    Co-Authors: Clifford B. Saper, Joshua J. Gooley, Ashley Schomer
    Abstract:

    Circadian rhythms of behavior and physiology can be entrained by daily cycles of restricted food availability, but the pathways that mediate food entrainment are unknown. The Dorsomedial Hypothalamic Nucleus (DMH) is critical for the expression of circadian rhythms and receives input from systems that monitor food availability. Here we report that restricted feeding synchronized the daily rhythm of DMH activity in rats such that c-Fos expression in the DMH was highest at scheduled mealtime. During food restriction, unlesioned rats showed a marked preprandial rise in locomotor activity, body temperature and wakefulness, and these responses were blocked by cell-specific lesions in the DMH. Furthermore, the degree of food entrainment correlated with the number of remaining DMH neurons, and lesions in cell groups surrounding the DMH did not block entrainment by food. These results establish that the neurons of the DMH have a critical role in the expression of food-entrainable circadian rhythms.

  • critical role of Dorsomedial Hypothalamic Nucleus in a wide range of behavioral circadian rhythms
    The Journal of Neuroscience, 2003
    Co-Authors: Thomas C. Chou, Joshua J. Gooley, Thomas E Scammell, Stephanie E Gaus, Clifford B. Saper
    Abstract:

    The suprachiasmatic Nucleus (SCN) contains the brain's circadian pacemaker, but mechanisms by which it controls circadian rhythms of sleep and related behaviors are poorly understood. Previous anatomic evidence has implicated the Dorsomedial Hypothalamic Nucleus (DMH) in circadian control of sleep, but this hypothesis remains untested. We now show that excitotoxic lesions of the DMH reduce circadian rhythms of wakefulness, feeding, locomotor activity, and serum corticosteroid levels by 78-89% while also reducing their overall daily levels. We also show that the DMH receives both direct and indirect SCN inputs and sends a mainly GABAergic projection to the sleep-promoting ventrolateral preoptic Nucleus, and a mainly glutamate-thyrotropin-releasing hormone projection to the wake-promoting lateral Hypothalamic area, including orexin (hypocretin) neurons. Through these pathways, the DMH may influence a wide range of behavioral circadian rhythms.

Kazuyoshi Tsutsui - One of the best experts on this subject based on the ideXlab platform.

  • Distribution of novel RFamide-related peptide-like immunoreactivity in the mouse central nervous system.
    Neuroscience letters, 2001
    Co-Authors: Kazuyoshi Ukena, Kazuyoshi Tsutsui
    Abstract:

    Recently, novel mammalian RFamide-related peptides (RFRPs) have been identified and suggested to increase prolactin release in the rodent. To assess possible functions of RFRPs, we investigated the distribution of RFRPs in the mouse central nervous system by immunochemical analyses. The quantitative analysis revealed that the concentration of RFRP-like substances was much higher in the brainstem and spinal cord than in other regions. Immunohistochemistry showed that RFRP-like immunoreactive perikarya were localized in the Dorsomedial Hypothalamic Nucleus, the lateral superior olive, and the Nucleus of the solitary tract. The dense networks of immunoreactive fibers were found in the lateral parabrachial Nucleus, the lateral reticular Nucleus, and the superficial layer of spinal trigeminal Nucleus and dorsal horn of the spinal cord. Thus, RFRPs may participate not only in neuroendocrine functions but also in behavioral, sensory, and autonomic functions.

Lee L. Bernardis - One of the best experts on this subject based on the ideXlab platform.

  • The Dorsomedial Hypothalamic Nucleus and its role in ingestive behavior and body weight regulation: lessons learned from lesioning studies.
    Physiology & behavior, 2002
    Co-Authors: Larry L. Bellinger, Lee L. Bernardis
    Abstract:

    This review article discusses the well-established role of the Dorsomedial Hypothalamic Nucleus (DMN) in feeding, drinking and body weight (BW) regulation. DMN lesions (L) in both weanling and mature rats of both sexes produce hypophagia, hypodipsia and reduced ponderal and linear growth in the presence of normal body composition. The growth reduction is not due to a deficient secretion of growth hormone, insulin-like growth factor-1, thyroxine, triiodothyronine or insulin. DMNL rats actively defend their lower BW (BW settling point) by becoming either hyper- or hypophagic, depending on the experimental manipulation, thereby defending both lean and fat mass. They also regulate their 24-h caloric intake, but they may overeat during the first hour of refeeding following a fast, possibly due to a reduced ability to monitor blood glucose or to respond to cholecystokinin (CCK). 2-Deoxy-D-glucose (2DG) increases c-fos expression in orexin-A neurons in the DMN, and DMNL eliminated the orexigenic effect of 2DG. DMNL rats on high-fat diets do not get as obese as controls, which may be due to a reduction of DMN neuropeptide Y (NPY). Rats lacking DMN CCK-A receptors are obese and have increased expression of NPY in the DMN, supporting earlier data that CCK may act at the DMN to suppress food intake. Excitotoxin studies showed that loss of DMN cell somata, and not fibers of passage, is important in the development of the DMNL syndrome. The DMN is a site where opioids increase food intake and knife-cut studies have shown that fibers traveling to/from the DMN are important in this response. An interaction of glucose and opioids in DMN may also be involved in the control of food intake. DMN knife cuts interrupting fibers in the posterior and ventral directions additively produce the hypophagia and reduced linear and ponderal growth observed after DMNL. Ventral cuts may interrupt important connections with the arcuate Nucleus. Lateral and posterior DMN cuts additively produce the hypodipsic effect seen after DMNL, but DMNL rats respond normally to all water-regulatory challenges, i.e., the hypophagia is not due to a primary hypodipsia. The DMN has been shown to be involved in the rat's feeding response to an imbalanced amino acid diet. These data show the DMN has an important role in many processes that control both food intake and BW regulation.

  • Effect of Dorsomedial Hypothalamic nuclei knife cuts on ingestive behavior.
    The American journal of physiology, 1999
    Co-Authors: Larry L. Bellinger, Lee L. Bernardis
    Abstract:

    Previous findings show that rats with electrolytic or excitotoxic lesions in the Dorsomedial Hypothalamic Nucleus (DMN) are hypophagic and hypodipsic and have reduced ponderal and linear growth but...

  • Reduced Femoral Geometry But Normal Biomechanics in the Dorsomedial Hypothalamic Nucleus-Lesioned Rat
    Physiology & behavior, 1999
    Co-Authors: R.j Kidd, Israel Ziv, Lee L. Bernardis
    Abstract:

    Bone geometry, structure, and biomechanical properties were investigated in a model of growth retardation, the Dorsomedial Hypothalamic Nucleus-lesioned (DMNL) weanling rat. Male weanling Sprague–Dawley rats received bilateral electrolytic lesions in the Dorsomedial Hypothalamic Nucleus (DMN) at age 27 days. Sham-operated rats served as controls. All rats were maintained postoperatively for 40 days. Upon sacrifice, DMNL rats weighed less (p < 0.01), were shorter (p < 0.01), and ate less (p < 0.01) when compared to controls, but their body composition was normal. The femora in DMNL were shorter (p < 0.01), had a smaller outer anteroposterior (AP) diameter (p < 0.04), polar moment of the area (p < 0.02), and msximal (p < 0.02) and minimal (p < 0.03) principal moment of the area when compared with sham-operated rats. Notably, mean torque at failure, torsional energy, stiffness, and maximal stress did not demonstrate statistically significant differences between the two groups. These data clearly show that despite the reduced size and bone growth, DMNL rats responded normally to the mechanical challenges applied to test bone biomechanical properties. The data, therefore, add to previous evidence and strengthen the hypothesis that DMNL rats are governed by an “organismic” set point.

  • The Dorsomedial Hypothalamic Nucleus revisited: 1998 update.
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York N.Y.), 1998
    Co-Authors: Lee L. Bernardis, Larry L. Bellinger
    Abstract:

    This article reviews data that have accumulated since the early 1970s on the role of the Dorsomedial Hypothalamic Nucleus (DMN) in neuroendocrine and autonomic homeostasis. Both the ventromedial Hypothalamic Nucleus (VMN) and the lateral Hypothalamic area (LHA) project to the DMN, which in turn projects to the paraventricular Nucleus of the hypothalamus (PVN), thus placing the DMN at an important nodal point of neuroendocrine/autonomic circuitries. The DMN is composed of cells and fibers containing neuropeptide Y (NPY), and the nutritional status (starvation-refeeding) is reflected in NPY levels of both VMN and DMN in Sprague-Dawley, Zucker (fa/fa), and corpulent rats (cp/cp JCR:LA). The DMN is involved in the final common pathway of corticotrophin-releasing hormone (CRH) secretion by the PVN, sympathetic nervous system outflow to the adrenal gland, and brown adipose tissue (BAT) thermogenesis. The DMN is also part of a "fear circuitry" regulating cardiovascular responses to stress such as myocardial blood flow and the tachycardia associated with the defense reaction. This appears to be mediated by a gamma amino butyric acid (GABA) mechanism. Although exhibiting reduced ponderal and linear growth and hypophagia and hypodipsia, the rat with DMN lesions (DMNL rat) has normal body composition, anabolic hormone levels, and intermediary metabolism, and it responds normally to numerous endocrine, nutritional, intra- and extracellular thirst and body weight-regulatory challenges. The DMNL rat shows normal efficiency of food utilization, but shows an attenuated response to the feeding-stimulatory effect of insulin. The only other lesion-induced abnormalities are hyperprolactinemia and a disrupted circadian corticosterone rhythm. The hyperprolactinemia in DMNL rats appears to be related to an attenuation of dopamine (DA). Rats with DMNL are capable of mating and can bear offspring, but there is a dramatic effect on litter size and other litter parameters that only improves when one parent is a DMNL rat. Antiaging effects produced by DMNL are evident in the prevention of age-associated microalbuminuria and kidney lesions, as well as, in prevention of the age-related decline in circulating insulin-like growth factor I (IGF-I). Recent evidence suggests that DMN, together with the VMN and the arcuate Nucleus (ARC) of the hypothalamus, may be part of the circuitry that is responsive to the feedback signal from adipose tissue by the hormone leptin. The above findings and others suggest that the DMN plays a diverse role in physiological regulatory processes.

  • The effect of Dorsomedial Hypothalamic Nucleus lesions on kidney function and structure after 1 and 12 months
    Physiology & behavior, 1993
    Co-Authors: Judith B. Van Liew, Bernice Noble, Lee L. Bernardis
    Abstract:

    According to the Dillman theory (17), aging results from a deterioration of metabolism that begins with an elevation of Hypothalamic receptor thresholds for feedback signals from the periphery. Three Hypothalamic areas are known to contain such receptors: the ventromedial and Dorsomedial Hypothalamic nuclei (DMN) and the lateral Hypothalamic area. We have hypothesized that selective destruction of those Hypothalamic areas might be followed by physiological changes associated with aging. Electrolytic bilateral DMN lesions were produced in male and female weanling rats. These rats were maintained for up to 13 months of age. Sham-operated rats served as controls. Food intake and body weight were monitored postoperatively and prior to sacrifice. Before sacrifice, tail blood and a 24-h urine samples were obtained. In accordance with previous findings, rats with DMN lesions showed dramatic reductions of ponderal growth and food intake but had normal body composition. Total protein and albumin excretion rates were significantly lower in rats with lesions. The fractional contribution of albumin to total urinary protein was also decreased in rats with lesions. Histological examination of the kidneys showed significantly less pathology in the kidneys of rats with DMN lesions; the severity of renal pathology was correlated directly with proteinuria. These changes were seen as early as 1 month after production of the lesion. The attenuation of age-related changes in kidney functions and structure in rats with lesions could be due to reduced food intake (dietary restriction is known to produce similar results), and/or a direct effect of the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Joshua J. Gooley - One of the best experts on this subject based on the ideXlab platform.

  • the Dorsomedial Hypothalamic Nucleus is critical for the expression of food entrainable circadian rhythms
    Nature Neuroscience, 2006
    Co-Authors: Clifford B. Saper, Joshua J. Gooley, Ashley Schomer
    Abstract:

    Circadian rhythms of behavior and physiology can be entrained by daily cycles of restricted food availability, but the pathways that mediate food entrainment are unknown. The Dorsomedial Hypothalamic Nucleus (DMH) is critical for the expression of circadian rhythms and receives input from systems that monitor food availability. Here we report that restricted feeding synchronized the daily rhythm of DMH activity in rats such that c-Fos expression in the DMH was highest at scheduled mealtime. During food restriction, unlesioned rats showed a marked preprandial rise in locomotor activity, body temperature and wakefulness, and these responses were blocked by cell-specific lesions in the DMH. Furthermore, the degree of food entrainment correlated with the number of remaining DMH neurons, and lesions in cell groups surrounding the DMH did not block entrainment by food. These results establish that the neurons of the DMH have a critical role in the expression of food-entrainable circadian rhythms.

  • critical role of Dorsomedial Hypothalamic Nucleus in a wide range of behavioral circadian rhythms
    The Journal of Neuroscience, 2003
    Co-Authors: Thomas C. Chou, Joshua J. Gooley, Thomas E Scammell, Stephanie E Gaus, Clifford B. Saper
    Abstract:

    The suprachiasmatic Nucleus (SCN) contains the brain's circadian pacemaker, but mechanisms by which it controls circadian rhythms of sleep and related behaviors are poorly understood. Previous anatomic evidence has implicated the Dorsomedial Hypothalamic Nucleus (DMH) in circadian control of sleep, but this hypothesis remains untested. We now show that excitotoxic lesions of the DMH reduce circadian rhythms of wakefulness, feeding, locomotor activity, and serum corticosteroid levels by 78-89% while also reducing their overall daily levels. We also show that the DMH receives both direct and indirect SCN inputs and sends a mainly GABAergic projection to the sleep-promoting ventrolateral preoptic Nucleus, and a mainly glutamate-thyrotropin-releasing hormone projection to the wake-promoting lateral Hypothalamic area, including orexin (hypocretin) neurons. Through these pathways, the DMH may influence a wide range of behavioral circadian rhythms.