The role of prostaglandin E2 synthesized in rat lateral parabrachial nucleus in LPS-induced fever

Abstract The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role in the normal maintenance of feeding behavior, because their loss leads to starvation. Viscerosensory stimuli result in neuronal activation of the PBN. However, the origin and neurochemical identity of the excitatory neuronal input to the PBN remain largely unexplored. Here, we hypothesize that hindbrain glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN, activation of which may lead to a reduction in feeding behavior. Our data, obtained from mice expressing the yellow fluorescent protein in GLP-1-producing neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of chow and palatable food and decreased body weight in rats. It also activated lPBN neurons, reflected by an increase in the number of c-Fos-positive cells in this region. Further support for an excitatory role of GLP-1 in the PBN is provided by electrophysiological studies showing a remarkable increase in firing of lPBN neurons after Exendin-4 application. We show that within the PBN, GLP-1R activation increased gene expression of 2 energy balance regulating peptides, calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application resulted in anorexia. Collectively, our molecular, anatomical, electrophysiological, pharmacological, and behavioral data provide evidence for a functional role of the GLP-1R for feeding control in the PBN.

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Adrenomedullin acts in the lateral parabrachial nucleus to increase arterial blood pressure through mechanisms mediated by glutamate and nitric oxide

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00172.2008 ◽

2008 ◽

Vol 295 (1) ◽

pp. R38-R44 ◽

Cited By ~ 1

Author(s):

Adrian Geambasu ◽

Teresa L. Krukoff

Keyword(s):

Nitric Oxide ◽

Calcium Channel ◽

Male Rats ◽

Parabrachial Nucleus ◽

Dependent Manner ◽

Pressor Effect ◽

Arterial Blood ◽

Lateral Parabrachial Nucleus ◽

Nos Inhibitors

Adrenomedullin (ADM) acts in a site-specific manner within autonomic centers of the brain to modulate mean arterial pressure (MAP). To determine the role of ADM in the pontine autonomic center, the lateral parabrachial nucleus (LPBN), we used urethane-anesthetized adult Sprague-Dawley male rats to test the hypothesis that ADM increases MAP at this site through glutamate- and nitric oxide (NO)-dependent mechanisms. ADM microinjected into the LPBN increased MAP in a dose-dependent manner. The pressor effect of ADM (0.01 pmol) had a peak value of 11.9 ± 1.9 mmHg at 2 min and lasted for 7 min. We demonstrated that ADM's effect is receptor mediated by blocking the effect with the ADM receptor antagonist, ADM22-52. We showed that glutamate mediates ADM's pressor response, as this response was blocked using coinjections of ADM with dizolcipine hydrogen maleate or 6-cyano-7-nitroquinoxaline-2,3-dione, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptor antagonists, respectively. We tested the roles of NO with coinjections of ADM with either N5-(1-iminoethyl)-l-ornithine or 7-nitroindazole monosodium salt, nonspecific and neuronal NO synthase (NOS) inhibitors, respectively; both inhibitors blocked ADM's pressor effect. Finally, we studied the role of calcium influx in ADM's pressor effect, as intracellular calcium is important in both glutamate and NO neurotransmission. ADM's effect was blocked when nifedipine, an L-type calcium channel blocker, was coinjected with ADM into the LPBN. This study is the first to show that ADM acts in the LPBN to increase MAP through mechanisms dependent on activation of ionotropic glutamate receptors, neuronal and endothelial NOS-mediated NO synthesis, and L-type calcium channel activation.

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Lateral parabrachial lesions attenuate ingestive effects of area postrema lesions

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.2.r306 ◽

1989 ◽

Vol 256 (2) ◽

pp. R306-R312 ◽

Cited By ~ 2

Author(s):

G. L. Edwards ◽

R. C. Ritter

Keyword(s):

Short Duration ◽

Area Postrema ◽

Parabrachial Nucleus ◽

Solitary Tract ◽

Palatable Food ◽

Lateral Parabrachial Nucleus ◽

Ingestive Behaviors

Lesions of the area postrema and adjacent nucleus of the solitary tract (AP lesions) cause rats to consume increased amounts of palatable food in short duration tests. Because the lateral parabrachial nucleus (lPBN) receives a prominent afferent projection from the AP and adjacent nucleus of the solitary tract, it is possible the lPBN plays a role in the altered ingestive behaviors observed in AP-lesioned rats. The present study examines the role of the lPBN in overingestion of highly palatable foods subsequent to AP lesions. We found that lesions of the lPBN alone did not cause rats to consume increased amounts of palatable food. Rather, when lPBN lesions were produced before AP lesions, increased intake of highly palatable food did not occur. Moreover, when AP-lesioned rats received subsequent lPBN lesions, the previously established overingestion of palatable foods was abolished. These results indicate that the lPBN is necessary in the pathogenesis of AP lesion-induced overingestion of highly palatable foods.

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