Hypothyroidism increases Fos immunoreactivity in cholinergic neurons of brain medullary dorsal vagal complex in rats

Hypo- or hyperthyroidism is associated with autonomic disorders. We studied Fos expression in the medullary dorsal motor nucleus of the vagus (DMV), nucleus tractus solitarii (NTS), and area postrema (AP) in four groups of rats with different thyroid states induced by a combination of drinking water and daily intraperitoneal injection for 1–4 wk: 1) tap water and vehicle; 2) 0.1% propylthiouracil (PTU) and vehicle; 3) PTU and thyroxine (T4; 2 μg/100 g); and 4) tap water and T4 (10 μg/100 g). The numbers of Fos immunoreactive (IR) positive neurons in the DMV, NTS, and AP were low in euthyroid rats but significantly higher in the 4-wk duration in hypothyroid rats, which were prevented by simultaneous T4 replacement. Hyperthyroidism had no effect on Fos expression in these areas. There were significant negative correlations between T4 levels and the numbers of Fos-IR-positive neurons in the DMV ( r = −0.6388, P < 0.008), NTS ( r = −0.6741, P < 0.003), and AP ( r = −0.5622, P < 0.004). Double staining showed that Fos immunoreactivity in the DMV of hypothyroid rats was mostly localized in choline acetyltransferase-containing neurons. Thyroid hormone receptors α1 and β2 were localized in the observed nuclei. These results indicate that thyroid hormone influences the DMV/NTS/AP neuronal activity, which may contribute to the vagal-related visceral disorders observed in hypothyroidism.

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Δ9-Tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00113.2003 ◽

2003 ◽

Vol 285 (3) ◽

pp. G566-G576 ◽

Cited By ~ 91

Author(s):

Marja D. Van Sickle ◽

Lorraine D. Oland ◽

Ken Mackie ◽

Joseph S. Davison ◽

Keith A. Sharkey

Keyword(s):

Receptor Antagonist ◽

Brain Stem ◽

Area Postrema ◽

Motor Nucleus ◽

Cb1 Receptors ◽

Dorsal Vagal Complex ◽

Dorsal Motor Nucleus ◽

Site Of Action ◽

Fos Expression ◽

The Brain

The aim of this study was to investigate the efficacy, receptor specificity, and site of action of Δ9-tetrahydrocannabinol (THC) as an antiemetic in the ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of cisplatin. The ED50 for retching was ∼0.1 mg/kg and for vomiting was 0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5 mg/kg ip) was ineffective. THC applied to the surface of the brain stem was sufficient to inhibit emesis induced by intragastric hypertonic saline. The site of action of THC in the brain stem was further assessed using Fos immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the solitary tract (NTS), but not other subnuclei of the NTS, was significantly reduced by THC rostral to obex. At the level of the obex, THC reduced Fos expression in the area postrema and the dorsal subnucleus of the NTS. The highest density of CB1 receptor immunoreactivity was found in the DMNX and the medial subnucleus of the NTS. Lower densities were observed in the area postrema and dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of staining in the commissural subnucleus of the NTS. These results show that THC selectively acts at CB1 receptors to reduce neuronal activation in response to emetic stimuli in specific regions of the dorsal vagal complex.

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Effect of brain stem NMDA-receptor blockade by MK-801 on behavioral and Fos responses to vagal satiety signals

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.277.4.r1104 ◽

1999 ◽

Vol 277 (4) ◽

pp. R1104-R1111 ◽

Cited By ~ 11

Author(s):

Huiyuan Zheng ◽

Lisa Kelly ◽

Laurel M. Patterson ◽

Hans-Rudolf Berthoud

Keyword(s):

Nmda Receptor ◽

Area Postrema ◽

Additive Model ◽

Nmda Receptor Antagonist ◽

Gastric Distension ◽

Motor Nucleus ◽

Sucrose Intake ◽

Mk 801 ◽

Dorsal Motor Nucleus ◽

Fos Expression

To test the possible role of N-methyl-d-aspartate (NMDA) glutamate receptors in the transmission of gastrointestinal satiety signals at the level of the nucleus of the solitary tract (NTS), we assessed the effect of fourth ventricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on short-term sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not affecting initial rate of intake, significantly increased sucrose intake during the later phase of the meal (10–30 min, 8.9 ± 1.0 vs. 2.9 ± 0.8 ml, P < 0.01). In the medial subnucleus of the NTS, the area postrema, and the dorsal motor nucleus, MK-801 did not reduce gastric distension-induced Fos expression and itself did not significantly induce Fos expression. In the dorsomedial, commissural, and gelatinosus subnuclei, MK-801 in itself produced significant Fos expression and significantly reduced (−75%, P < 0.05) the ability of gastric distension to induce Fos expression, assuming an additive model with two separate populations of neurons activated by distension and the blocker. Although these results are consistent with NMDA receptor-mediated glutamatergic transmission of vagal satiety signals in general, they lend limited support for such a role in the transmission of specific gastric distension signals.

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Glucose does not activate nonadrenergic, noncholinergic inhibitory neurons in the rat stomach

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00561.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. R742-R750 ◽

Cited By ~ 16

Author(s):

Min Shi ◽

Allison R. Jones ◽

Manuel Ferreira ◽

Niaz Sahibzada ◽

Richard A. Gillis ◽

...

Keyword(s):

Gastric Motility ◽

No Reduction ◽

Cholinergic Neurons ◽

Inhibitory Neurons ◽

Motor Nucleus ◽

Dorsal Motor Nucleus ◽

The Central Nervous System ◽

Fos Expression ◽

Oxide Synthase

We reported previously that intravenously administered d-glucose acts in the central nervous system to inhibit gastric motility induced by hypoglycemia in anesthetized rats. The purpose of this study was to determine whether this effect is due to inhibition of dorsal motor nucleus of the vagus (DMV) cholinergic motoneurons, which synapse with postganglionic cholinergic neurons, or to excitation of DMV cholinergic neurons, which synapse with postganglionic nonadrenergic, noncholinergic (NANC) neurons, particularly nitrergic neurons. Three approaches were employed: 1) assessment of the efficacy of d-glucose-induced inhibition of gastric motility in hypoglycemic rats with and without inhibition of nitric oxide synthase [10 mg/kg iv nitro-l-arginine methyl ester (l-NAME)], 2) assessment of the efficacy of intravenous bethanechol (30 μg·kg−1·min−1) to stimulate gastric motility in hypoglycemic rats during the time of d-glucose-induced inhibition of gastric motility, and 3) determination of c-Fos expression in DMV neurons after intravenous d-glucose was administered to normoglycemic rats. Results obtained demonstrated that l-NAME treatment had no effect on d-glucose-induced inhibition of gastric motility; there was no reduction in the efficacy of intravenous bethanechol to increase gastric motility, and c-Fos expression was not induced by d-glucose in DMV neurons that project to the stomach. These findings indicate that excitation of DMV cholinergic motoneurons that synapse with postganglionic NANC neurons is not a significant contributing component of d-glucose-induced inhibition of gastric motility.

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Swallowing reflex and brain stem neurons activated by superior laryngeal nerve stimulation in the mouse

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.2.g191 ◽

2001 ◽

Vol 280 (2) ◽

pp. G191-G200 ◽

Cited By ~ 33

Author(s):

Q. Sang ◽

Raj K. Goyal

Keyword(s):

Area Postrema ◽

Superior Laryngeal Nerve ◽

Laryngeal Nerve ◽

Nucleus Ambiguus ◽

Reticular Nucleus ◽

Motor Nucleus ◽

Esophageal Peristalsis ◽

Primary Peristalsis ◽

Dorsal Motor Nucleus ◽

Fos Expression

The purpose of the present study was to identify vagal subnuclei that participate in reflex swallowing in response to electrical stimulation of the left superior laryngeal nerve (SLN). SLN stimulation at 10 Hz evoked primary peristalsis, including oropharyngeal and esophageal peristalsis, and LES relaxation. It also induced c- fos expression in interneurons in the interstitial (SolI), intermediate (SolIM), central (SolCe), dorsomedial (SolDM) and commissural (SolC) solitary subnuclei. Neurons in parvicellular reticular nucleus (PCRt) and area postrema (AP) and motoneurons in the semicompact (NAsc), loose (NAl), and compact (NAc) formations of the nucleus ambiguus and both rostral (DMVr) and caudal (DMVc) parts of the dorsal motor nucleus of vagus were also activated. The activated neurons represent all neurons concerned with afferent SLN-mediated reflexes, including the swallowing-related neurons. SLN stimulation at 5 Hz elicited oropharyngeal and LES but not esophageal responses and evoked c- fos expression in neurons in SolI, SolIM, SolDM, PCRt, AP, NAsc, NAl, and DMVc but not in SolCe, NAc, or DMVr. These data are consistent with the role of SolI, SolIM, SolDM, NAsc, NAl, and DMVc circuit in oropharyngeal peristalsis and LES relaxation and SolCe, NAc, DMVc, and DMVr in esophageal peristalsis and LES responses.

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