scholarly journals Effects of Feeding-Related Peptides on Neuronal Oscillation in the Ventromedial Hypothalamus

2019 ◽  
Vol 8 (3) ◽  
pp. 292 ◽  
Author(s):  
Kamon Iigaya ◽  
Yoshino Minoura ◽  
Hiroshi Onimaru ◽  
Sayumi Kotani ◽  
Masahiko Izumizaki
Keyword(s):  
Sympathetic Nerve Activity ◽  
Ventromedial Hypothalamus ◽  
Glucose Sensing ◽  
Corticotropin Releasing Factor ◽  
Nerve Activity ◽  
Pituitary Adenylate Cyclase ◽  
Neuronal Oscillation ◽  
Extracellular Glucose ◽  
Frequency Changes ◽  
The Brain

The ventromedial hypothalamus (VMH) plays an important role in feeding behavior, obesity, and thermoregulation. The VMH contains glucose-sensing neurons, the firing of which depends on the level of extracellular glucose and which are involved in maintaining the blood glucose level via the sympathetic nervous system. The VMH also expresses various receptors of the peptides related to feeding. However, it is not well-understood whether the action of feeding-related peptides mediates the activity of glucose-sensing neurons in the VMH. In the present study, we examined the effects of feeding-related peptides on the burst-generating property of the VMH. Superfusion with insulin, pituitary adenylate cyclase-activating polypeptide, corticotropin-releasing factor, and orexin increased the frequency of the VMH oscillation. In contrast, superfusion with leptin, cholecystokinin, cocaine- and amphetamine-regulated transcript, galanin, ghrelin, and neuropeptide Y decreased the frequency of the oscillation. Our findings indicated that the frequency changes of VMH oscillation in response to the application of feeding-related peptides showed a tendency similar to changes of sympathetic nerve activity in response to the application of these substances to the brain.

scholarly journals Insulin blunts the response of glucose-excited neurons in the ventrolateral-ventromedial hypothalamic nucleus to decreased glucose

2009 ◽  
Vol 296 (5) ◽  
pp. E1101-E1109 ◽  
Author(s):  
Victoria E. Cotero ◽  
Vanessa H. Routh
Keyword(s):  
Energy Homeostasis ◽  
Ventromedial Hypothalamus ◽  
Glucose Sensing ◽  
Hypothalamic Nucleus ◽  
Compensatory Mechanisms ◽  
Glucose Levels ◽  
Compound C ◽  
Obesity And Diabetes ◽  
Extracellular Glucose ◽  
Pi3k Signaling Pathway

Insulin signaling is dysfunctional in obesity and diabetes. Moreover, central glucose-sensing mechanisms are impaired in these diseases. This is associated with abnormalities in hypothalamic glucose-sensing neurons. Glucose-sensing neurons reside in key areas of the brain involved in glucose and energy homeostasis, such as the ventromedial hypothalamus (VMH). Our results indicate that insulin opens the KATP channel on VMH GE neurons in 5, 2.5, and 0.1 mM glucose. Furthermore, insulin reduced the sensitivity of VMH GE neurons to a decrease in extracellular glucose level from 2.5 to 0.1 mM. This change in the glucose sensitivity in the presence of insulin was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (10 nM) but not by the mitogen-activated kinase (MAPK) inhibitor PD-98059 (PD; 50 μM). Finally, neither the AMPK inhibitor compound C nor the AMPK activator AICAR altered the activity of VMH GE neurons. These data suggest that insulin attenuates the ability of VMH GE neurons to sense decreased glucose via the PI3K signaling pathway. Furthermore, these data are consistent with the role of insulin as a satiety factor. That is, in the presence of insulin, glucose levels must decline further before GE neurons respond. Thus, the set point for detection of glucose deficit and initiation of compensatory mechanisms would be lowered.

scholarly journals Arcuate nucleus injection of an anti-insulin affibody prevents the sympathetic response to insulin

2013 ◽  
Vol 304 (11) ◽  
pp. H1538-H1546 ◽  
Author(s):  
Brittany S. Luckett ◽  
Jennifer L. Frielle ◽  
Lawrence Wolfgang ◽  
Sean D. Stocker
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Arcuate Nucleus ◽  
Insulin Receptors ◽  
Ventromedial Hypothalamus ◽  
Intracerebroventricular Injection ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Sympathetic Response ◽  
Sprague Dawley Rats

Accumulating evidence suggests that insulin acts within the hypothalamus to alter sympathetic nerve activity (SNA) and baroreflex function. Although insulin receptors are widely expressed across the hypothalamus, recent evidence suggests that neurons of the arcuate nucleus (ARC) play an important role in the sympathoexcitatory response to insulin. The purpose of the present study was to determine whether circulating insulin acts directly in the ARC to elevate SNA. In anesthetized male Sprague-Dawley rats (275–425 g), the action of insulin was neutralized by microinjection of an anti-insulin affibody (1 ng/40 nl). To verify the efficacy of the affibody, ARC pretreatment with injection of the anti-insulin affibody completely prevented the increase in lumbar SNA produced by ARC injection of insulin. Next, ARC pretreatment with the anti-insulin affibody attenuated the lumbar sympathoexcitatory response to intracerebroventricular injection of insulin. Third, a hyperinsulinemic-euglycemic clamp increased lumbar, but not renal, SNA in animals that received ARC injection of a control affibody. However, this sympathoexcitatory response was absent in animals pretreated with the anti-insulin affibody in the ARC. Injection of the anti-insulin affibody in the adjacent ventromedial hypothalamus did not alter the sympathoexcitatory response to insulin. The ability of the anti-insulin affibody to prevent the sympathetic effects of insulin cannot be attributed to a general inactivation or nonspecific effect on ARC neurons as the affibody did not alter the sympathoexcitatory response to ARC disinhibition by gabazine. Collectively, these findings suggest that circulating insulin acts within the ARC to increase SNA.

PACAP is expressed in sympathoexcitatory bulbospinal C1 neurons of the brain stem and increases sympathetic nerve activity in vivo

2008 ◽  
Vol 294 (4) ◽  
pp. R1304-R1311 ◽  
Author(s):  
Melissa M. J. Farnham ◽  
Qun Li ◽  
Ann K. Goodchild ◽  
Paul M. Pilowsky
Keyword(s):  
Blood Pressure ◽  
Brain Stem ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Intrathecal Administration ◽  
Ventrolateral Medulla ◽  
Cell Group ◽  
Nerve Activity ◽  
The Brain

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide present in the rat brain stem. The extent of its localization within catecholaminergic groups and bulbospinal sympathoexcitatory neurons is not established. Using immunohistochemistry and in situ hybridization, we determined the extent of any colocalization with catecholaminergic and/or bulbospinal projections from the brain stem was determined. PACAP mRNA was found in tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the C1-C3 cell groups. In the rostral ventrolateral medulla (RVLM), PACAP mRNA was found in 84% of the TH-ir neurons and 82% of bulbospinal TH-ir neurons. The functional significance of these PACAP mRNA positive bulbospinal neurons was tested by intrathecal administration of PACAP-38 in anaesthetized rats. Splanchnic sympathetic nerve activity doubled (110%) and heart rate rose significantly (19%), although blood pressure was unaffected. In addition, as previously reported, PACAP was found in the A1 cell group but not in the A5 cell group or in the locus coeruleus. The RVLM is the primary site responsible for the tonic and reflex control of blood pressure through the activity of bulbospinal presympathetic neurons, the majority of which contain TH. The results indicate 1) that pontomedullary neurons containing both TH and PACAP that project to the intermediolateral cell column originate from C1-C3 and not A5, and 2) intrathecal PACAP-38 causes a prolonged, sympathoexcitatory effect.

Increased osmolality of conscious water-deprived rats supports arterial pressure and sympathetic activity via a brain action

2005 ◽  
Vol 288 (5) ◽  
pp. R1248-R1255 ◽  
Author(s):  
Virginia L. Brooks ◽  
Yue Qi ◽  
Theresa L. O'Donaughy
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Sympathetic Activity ◽  
Carotid Arteries ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Fluid Infusion ◽  
Hypotonic Fluid ◽  
Control Heart ◽  
The Brain

To test the hypothesis that high osmolality acts in the brain to chronically support mean arterial pressure (MAP) and lumbar sympathetic nerve activity (LSNA), the osmolality of blood perfusing the brain was reduced in conscious water-deprived and water-replete rats by infusion of hypotonic fluid via bilateral nonoccluding intracarotid catheters. In water-deprived rats, the intracarotid hypotonic infusion, estimated to lower osmolality by ∼2%, decreased MAP by 9 ± 1 mmHg and LSNA to 86 ± 7% of control; heart increased by 25 ± 8 beats per minute (bpm) (all P < 0.05). MAP, LSNA, and heart rate did not change when the hypotonic fluid was infused intravenously. The intracarotid hypotonic fluid infusion was also ineffective in water-replete rats. Prior treatment with a V1 vasopressin antagonist did not alter the subsequent hypotensive and tachycardic effects of intracarotid hypotonic fluid infusion in water-deprived rats. In summary, acute decreases in osmolality of the carotid blood of water-deprived, but not water-replete, rats decreases MAP and LSNA and increases heart rate. These data support the hypothesis that the elevated osmolality induced by water deprivation acts via a region perfused by the carotid arteries, presumably the brain, to tonically increase MAP and LSNA and suppress heart rate.

scholarly journals “Real-time” imaging of cortical and subcortical sites of cardiovascular control: concurrent recordings of sympathetic nerve activity and fMRI in awake subjects

2016 ◽  
Vol 116 (3) ◽  
pp. 1199-1207 ◽  
Author(s):  
Vaughan G. Macefield ◽  
Luke A. Henderson
Keyword(s):  
Orbitofrontal Cortex ◽  
Sympathetic Nerve ◽  
Signal Intensity ◽  
Sympathetic Nerve Activity ◽  
Human Subjects ◽  
Ventrolateral Medulla ◽  
Bold Signal ◽  
Nerve Activity ◽  
The Right ◽  
The Brain

We review our approach to functionally identifying cortical and subcortical areas involved in the generation of spontaneous fluctuations in sympathetic outflow to muscle or skin. We record muscle sympathetic nerve activity (MSNA) or skin sympathetic nerve activity (SSNA), via a tungsten microelectrode inserted percutaneously into the common peroneal nerve, at the same time as performing functional magnetic resonance imaging (fMRI) of the brain. By taking advantage of the neurovascular coupling delay associated with BOLD (blood oxygen level dependent) fMRI, and the delay associated with conduction of a burst of sympathetic impulses to the peripheral recording site, we can identify structures in which BOLD signal intensity covaries with MSNA or SSNA. Using this approach, we found MSNA-coupled increases in BOLD signal intensity in the mid-insula and dorsomedial hypothalamus on the left side, and in dorsolateral prefrontal cortex, posterior cingulate cortex, precuneus, ventromedial hypothalamus and rostral ventrolateral medulla on both sides. Conversely, spontaneous bursts of SSNA were positively correlated with BOLD signal intensity in the ventromedial thalamus and posterior insula on the left side, and in the anterior insula, orbitofrontal cortex and frontal cortex on the right side, and in the mid-cingulate cortex and precuneus on both sides. Inverse relationships were observed between MSNA and BOLD signal intensity in the right ventral insula, nucleus tractus solitarius and caudal ventrolateral medulla, and between SSNA and signal intensity in the left orbitofrontal cortex. These results emphasize the contributions of cortical regions of the brain to sympathetic outflow in awake human subjects, and the extensive interactions between cortical and subcortical regions in the ongoing regulation of sympathetic nerve activity to muscle and skin in awake human subjects.

The actions of Shiga toxin-2 administration into the brain on renal sympathetic nerve activity

2011 ◽  
Vol 16 (3) ◽  
pp. 382-388 ◽  
Author(s):  
Akio Nakamura ◽  
Akira Imaizumi ◽  
Takao Kohsaka ◽  
Chunlong Huang ◽  
Chunhua Huang ◽  
...  
Keyword(s):  
Shiga Toxin ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Shiga Toxin 2 ◽  
The Brain ◽  
Renal Sympathetic

scholarly journals Effects of glucose and insulin on glucokinase activity in rat hypothalamus

2007 ◽  
Vol 193 (2) ◽  
pp. 259-267 ◽  
Author(s):  
Carmen Sanz ◽  
Isabel Roncero ◽  
Patricia Vázquez ◽  
M Angeles Navas ◽  
Enrique Blázquez
Keyword(s):  
Enzyme Activities ◽  
Physiological Model ◽  
Ventromedial Hypothalamus ◽  
Glucose Sensing ◽  
Biological Models ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain ◽  
Hypothalamic Slices

In an attempt to study the role of glucokinase (GK) and the effects of glucose and peptides on GK gene expression and on the activity of this enzyme in the hypothalamus, we used two kinds of biological models: hypothalamic GT1-7 cells and rat hypothalamic slices. The expression of the GK gene in GT1-7 cells was reduced by insulin (INS) and was not modified by different glucose concentrations, while GK enzyme activities were significantly reduced by the different peptides. Interestingly, a distinctive pattern of GK activities between the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) were found, with higher enzyme activities in the VMH as the glucose concentrations rose, while LH enzyme activities decreased at 2.8 and 20 mM glucose, the latter effect being prevented by incubation with INS. These effects were produced only by d-glucose and the modifications found were due to GK, but not to other hexokinases. In addition, GK activities in the VMH and the LH were reduced by glucagon-like peptide 1, leptin, orexin B, INS, and neuropeptide Y (NPY), but this effect was only statistically significant for NPY in LH. Our results indicate that the effects of both glucose and peptides occur on GK enzyme activities rather than on GK gene transcription. Moreover, the effects of glucose and INS on GK activity suggest that in the brain GK behaves in a manner opposite to that in the liver, which might facilitate its role in glucose sensing. Finally, hypothalamic slices seem to offer a good physiological model to discriminate the effects between different areas.

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