Brain activation following peripheral administration of the GLP-1 receptor agonist exendin-4

2011 ◽  
Vol 301 (4) ◽  
pp. R1011-R1024 ◽  
Author(s):  
Elena-Dana Baraboi ◽  
David H. St-Pierre ◽  
Julie Shooner ◽  
Elena Timofeeva ◽  
Denis Richard
Keyword(s):  
Vagus Nerve ◽  
Mrna Expression ◽  
Supraoptic Nucleus ◽  
Brain Activation ◽  
Brain Regions ◽  
Nodose Ganglion ◽  
Central Regions ◽  
The Brain ◽  
Pituitary Adrenal Axis

The aim of our study was to investigate the anorectic and brain stimulatory effects of various doses of exendin-4 (Ex-4) and to investigate the role of the vagus nerve in Ex-4-induced brain activation. A dose-related increase in c- fos mRNA expression was observed following Ex-4 administration (0.155–15.5 μg/kg). Doses of Ex-4 that caused anorexia without aversive effects (0.155, 0.775 μg/kg) induced c- fos expression in the hypothalamic arcuate and paraventricular (PVH; parvocellular) nuclei as well as in the limbic and brainstem structures. Doses of Ex-4 that caused aversion (1.55, 15.5 μg/kg) stimulated the same regions (in a more intense way) and additionally activated the magnocellular hypothalamic structures (supraoptic nucleus and PVH magnocellular). The brain c- fos pattern induced by Ex-4 showed both similarities and differences with that induced by refeeding. Subdiaphragmatic vagotomy significantly blunted the stimulation of c- fos mRNA expression induced by Ex-4 in the nodose ganglion, the medial part of nucleus of the solitary tract, and the parvocellular division of the PVH. Pretreatment with Ex-9-39 (330 μg/kg ip) impaired the neuronal activation evoked by Ex-4 in all brain regions and in the nodose ganglion. Effects of Ex-4 on hypothalamic-pituitary-adrenal axis activity were not altered by vagotomy. Results of this study demonstrate and relate the anorectic and brain stimulatory effects of aversive and nonaversive doses of Ex-4 and indicate that the activation of specific central regions induced by the peripheral administration of Ex-4 is, at least in part, dependent on the integrity of the vagus nerve.

Role of adrenal catecholamines in cerebrovasodilation evoked from brain stem

1987 ◽  
Vol 252 (6) ◽  
pp. H1183-H1191
Author(s):  
C. Iadecola ◽  
P. M. Lacombe ◽  
M. D. Underwood ◽  
T. Ishitsuka ◽  
D. J. Reis
Keyword(s):  
Brain Function ◽  
Blood Gases ◽  
Brain Regions ◽  
Elevated Plasma ◽  
Regional Cerebral Blood ◽  
Medullary Reticular Formation ◽  
Alpha Chloralose ◽  
The Brain ◽  
Stimulation Of

We studied whether adrenal medullary catecholamines (CAs) contribute to the metabolically linked increase in regional cerebral blood flow (rCBF) elicited by electrical stimulation of the dorsal medullary reticular formation (DMRF). Rats were anesthetized (alpha-chloralose, 30 mg/kg), paralyzed, and artificially ventilated. The DMRF was electrically stimulated with intermittent trains of pulses through microelectrodes stereotaxically implanted. Blood gases were controlled and, during stimulation, arterial pressure was maintained within the autoregulated range for rCBF. rCBF and blood-brain barrier (BBB) permeability were determined in homogenates of brain regions by using [14C]iodoantipyrine and alpha-aminoisobutyric acid (AIB), respectively, as tracers. Plasma CAs (epinephrine and norepinephrine) were measured radioenzymatically. DMRF stimulation increased rCBF throughout the brain (n = 5; P less than 0.01, analysis of variance) and elevated plasma CAs substantially (n = 4). Acute bilateral adrenalectomy abolished the increase in plasma epinephrine (n = 4), reduced the increases in flow (n = 6) in cerebral cortex (P less than 0.05), and abolished them elsewhere in brain (P greater than 0.05). Comparable effects on rCBF were obtained by selective adrenal demedullation (n = 7) or pretreatment with propranolol (1.5 mg/kg iv) (n = 5). DMRF stimulation did not increase the permeability of the BBB to AIB (n = 5). We conclude that the increases in rCBF elicited from the DMRF has two components, one dependent on, and the other independent of CAs. Since the BBB is impermeable to CAs and DMRF stimulation fails to open the BBB, the results suggest that DMRF stimulation allows, through a mechanism not yet determined, circulating CAs to act on brain and affect brain function.

scholarly journals Neural Substrates of Social Status Inference: Roles of Medial Prefrontal Cortex and Superior Temporal Sulcus

2014 ◽  
Vol 26 (5) ◽  
pp. 1131-1140 ◽  
Author(s):  
Malia Mason ◽  
Joe C. Magee ◽  
Susan T. Fiske
Keyword(s):  
Social Order ◽  
Neural Substrates ◽  
Brain Regions ◽  
Third Party ◽  
Social Interdependence ◽  
Medial Pfc ◽  
State Inference ◽  
The Brain ◽  
Track Status

The negotiation of social order is intimately connected to the capacity to infer and track status relationships. Despite the foundational role of status in social cognition, we know little about how the brain constructs status from social interactions that display it. Although emerging cognitive neuroscience reveals that status judgments depend on the intraparietal sulcus, a brain region that supports the comparison of targets along a quantitative continuum, we present evidence that status judgments do not necessarily reduce to ranking targets along a quantitative continuum. The process of judging status also fits a social interdependence analysis. Consistent with third-party perceivers judging status by inferring whose goals are dictating the terms of the interaction and who is subordinating their desires to whom, status judgments were associated with increased recruitment of medial pFC and STS, brain regions implicated in mental state inference.

scholarly journals The NCX3 Isoform of the Na+/Ca2+ Exchanger Contributes to Neuroprotection Elicited by Ischemic Postconditioning

2010 ◽  
Vol 31 (1) ◽  
pp. 362-370 ◽  
Author(s):  
Giuseppe Pignataro ◽  
Elga Esposito ◽  
Ornella Cuomo ◽  
Rossana Sirabella ◽  
Francesca Boscia ◽  
...  
Keyword(s):  
Brain Regions ◽  
Ischemic Postconditioning ◽  
Intracerebroventricular Infusion ◽  
Ionic Transporters ◽  
Relevant Role ◽  
Ischemic Episode ◽  
Study Support ◽  
Interfering Rna ◽  
The Brain

It has been recently shown that a short sublethal brain ischemia subsequent to a prolonged harmful ischemic episode may confer ischemic neuroprotection, a phenomenon termed ischemic postconditioning. Na+/Ca2+ exchanger (NCX) isoforms, NCX1, NCX2, and NCX3, are plasma membrane ionic transporters widely distributed in the brain and involved in the control of Na+ and Ca2+ homeostasis and in the progression of stroke damage. The objective of this study was to evaluate the role of these three proteins in the postconditioning-induced neuroprotection. The NCX protein and mRNA expression was evaluated at different time points in the ischemic temporoparietal cortex of rats subjected to tMCAO alone or to tMCAO plus ischemic postconditioning. The results of this study showed that NCX3 protein and ncx3 mRNA were upregulated in those brain regions protected by postconditioning treatment. These changes in NCX3 expression were mediated by the phosphorylated form of the ubiquitously expressed serine/threonine protein kinase p-AKT, as the p-AKT inhibition prevented NCX3 upregulation. The relevant role of NCX3 during postconditioning was further confirmed by results showing that NCX3 silencing, induced by intracerebroventricular infusion of small interfering RNA (siRNA), partially reverted the postconditioning-induced neuroprotection. The results of this study support the idea that the enhancement of NCX3 expression and activity might represent a reasonable strategy to reduce the infarct extension after stroke.

scholarly journals The Role of Corticotropin-Releasing Hormone at Peripheral Nociceptors: Implications for Pain Modulation

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 623
Author(s):  
Haiyan Zheng ◽  
Ji Yeon Lim ◽  
Jae Young Seong ◽  
Sun Wook Hwang
Keyword(s):  
Signal Transmission ◽  
Brain Regions ◽  
Pain Modulation ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Inhibitory Function ◽  
Peripheral Pain ◽  
Functional Profiles ◽  
Pituitary Adrenal Axis

Peripheral nociceptors and their synaptic partners utilize neuropeptides for signal transmission. Such communication tunes the excitatory and inhibitory function of nociceptor-based circuits, eventually contributing to pain modulation. Corticotropin-releasing hormone (CRH) is the initiator hormone for the conventional hypothalamic-pituitary-adrenal axis, preparing our body for stress insults. Although knowledge of the expression and functional profiles of CRH and its receptors and the outcomes of their interactions has been actively accumulating for many brain regions, those for nociceptors are still under gradual investigation. Currently, based on the evidence of their expressions in nociceptors and their neighboring components, several hypotheses for possible pain modulations are emerging. Here we overview the historical attention to CRH and its receptors on the peripheral nociception and the recent increases in information regarding their roles in tuning pain signals. We also briefly contemplate the possibility that the stress-response paradigm can be locally intrapolated into intercellular communication that is driven by nociceptor neurons. Such endeavors may contribute to a more precise view of local peptidergic mechanisms of peripheral pain modulation.

scholarly journals Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1018
Author(s):  
Caitlyn A. Mullins ◽  
Ritchel B. Gannaban ◽  
Md Shahjalal Khan ◽  
Harsh Shah ◽  
Md Abu B. Siddik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Homeostasis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Obesity Prevalence ◽  
Beneficial Effects ◽  
The Brain

Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.

Stimuli and consequences of dendritic release of oxytocin within the brain

2007 ◽  
Vol 35 (5) ◽  
pp. 1252-1257 ◽  
Author(s):  
I.D. Neumann
Keyword(s):  
Paraventricular Nucleus ◽  
Stress Responses ◽  
Supraoptic Nucleus ◽  
Brain Regions ◽  
Model System ◽  
Intracerebral Microdialysis ◽  
Psychotherapeutic Intervention ◽  
Psychiatric Illnesses ◽  
Oxytocin Release ◽  
The Brain

The brain oxytocin system has served as a distinguished model system in neuroendocrinology to study detailed mechanisms of intracerebral release, in particular of somatodendritic release, and its behavioural and neuroendocrine consequences. It has been shown that oxytocin is released within various brain regions, but evidence for dendritic release is limited to the main sites of oxytocin synthesis, i.e. the hypothalamic SON (supraoptic nucleus) and PVN (paraventricular nucleus). In the present paper, stimuli of dendritic release of oxytocin and the related neuropeptide vasopressin are discussed, including parturition and suckling, i.e. the period of a highly activated brain oxytocin system. Also, exposure to various pharmacological, psychological or physical stressors triggers dendritic oxytocin release, as monitored by intracerebral microdialysis within the SON and PVN during ongoing behavioural testing. So far, dendritic release of the neuropeptide has only been demonstrated within the hypothalamus, but intracerebral oxytocin release has also been found within the central amygdala and the septum in response to various stimuli including stressor exposure. Such a locally released oxytocin modulates physiological and behavioural reproductive functions, emotionality and hormonal stress responses, as it exerts, for example, pro-social, anxiolytic and antistress actions within restricted brain regions. These discoveries make oxytocin a promising neuromodulator of the brain for psychotherapeutic intervention and treatment of numerous psychiatric illnesses, for example, anxiety-related diseases, social phobia, autism and postpartum depression.

Novel pathway for LPS-induced afferent vagus nerve activation: Possible role of nodose ganglion

2005 ◽  
Vol 120 (1-2) ◽  
pp. 104-107 ◽  
Author(s):  
Toru Hosoi ◽  
Yasunobu Okuma ◽  
Tadashi Matsuda ◽  
Yasuyuki Nomura
Keyword(s):  
Vagus Nerve ◽  
Nodose Ganglion ◽  
Afferent Vagus

Transcutaneous Vagus Nerve Stimulation Enhances Post-error Slowing

2015 ◽  
Vol 27 (11) ◽  
pp. 2126-2132 ◽  
Author(s):  
Roberta Sellaro ◽  
Jelle W. R. van Leusden ◽  
Klodiana-Daphne Tona ◽  
Bart Verkuil ◽  
Sander Nieuwenhuis ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Direct Evidence ◽  
Noradrenergic System ◽  
Group Design ◽  
Transcutaneous Vagus Nerve Stimulation ◽  
The Brain ◽  
Single Blind

People tend to slow down after they commit an error, a phenomenon known as post-error slowing (PES). It has been proposed that slowing after negative feedback or unforeseen errors is linked to the activity of the locus coeruleus–norepinephrine (LC–NE) system, but there is little direct evidence for this hypothesis. Here, we assessed the causal role of the noradrenergic system in modulating PES by applying transcutaneous vagus nerve stimulation (tVNS), a new noninvasive and safe method to stimulate the vagus nerve and to increase NE concentrations in the brain. A single-blind, sham-controlled, between-group design was used to assess the effect of tVNS in healthy young volunteers (n = 40) during two cognitive tasks designed to measure PES. Results showed increased PES during active tVNS, as compared with sham stimulation. This effect was of similar magnitude for the two tasks. These findings provide evidence for an important role of the noradrenergic system in PES.

Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress

2016 ◽  
Vol 94 (10) ◽  
pp. 1074-1082 ◽  
Author(s):  
Dragan Hrncic ◽  
Jelena Mikić ◽  
Aleksandra Rasic-Markovic ◽  
Milica Velimirović ◽  
Tihomir Stojković ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Open Field ◽  
Wistar Rats ◽  
Brain Regions ◽  
Oxidative Status ◽  
Standard Diet ◽  
Male Wistar Rats ◽  
Brain Oxidative Stress ◽  
The Brain

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light–dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

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