Vagal modulation of intestinal afferent sensitivity to systemic LPS in the rat

2007 ◽  
Vol 292 (5) ◽  
pp. G1213-G1220 ◽  
Author(s):  
C. Y. Liu ◽  
M. H. Mueller ◽  
D. Grundy ◽  
M. E. Kreis
Keyword(s):  
Systemic Blood Pressure ◽  
Feedback Mechanism ◽  
Afferent Nerve ◽  
Vagal Afferents ◽  
Partial Recovery ◽  
Before And After ◽  
The Central Nervous System ◽  
Vagal Afferent ◽  
Nerve Discharge

The central nervous system modulates inflammation in the gastrointestinal tract via efferent vagal pathways. We hypothesized that these vagal efferents receive synaptic input from vagal afferents, representing an autonomic feedback mechanism. The consequence of this vagovagal reflex for afferent signal generation in response to LPS was examined in the present study. Different modifications of the vagal innervation or sham procedures were performed in anesthetized rats. Extracellular mesenteric afferent nerve discharge and systemic blood pressure were recorded in vivo before and after systemic administration of LPS (6 mg/kg iv). Mesenteric afferent nerve discharge increased dramatically following LPS, which was unchanged when vagal efferent traffic was eliminated by acute vagotomy. In chronically vagotomized animals, to eliminate both vagal afferent and efferent traffic, the increase in afferent firing 3.5 min after LPS was reduced to 3.2 ± 2.5 impulses/s above baseline compared with 42.2 ± 2.0 impulses/s in controls ( P < 0.001). A similar effect was observed following perivagal capsaicin, which was used to eliminate vagal afferent traffic only. LPS also caused a transient hypotension (<10 min), a partial recovery, and then persistent hypertension that was exacerbated by all three procedures. Mechanosensitivity was increased 15 min following LPS but had recovered at 30 min in all subgroups except for the chronic vagotomy group. In conclusion, discharge in capsaicin-sensitive mesenteric vagal afferents is augmented following systemic LPS. This activity, through a vagovagal pathway, helps to attenuate the effects of septic shock. The persistent hypersensitivity to mechanical stimulation after chronic vagal denervation suggests that the vagus exerts a regulatory influence on spinal afferent sensitization following LPS.

GABABR expressed on vagal afferent neurones inhibit gastric mechanosensitivity in ferret proximal stomach

2001 ◽  
Vol 281 (6) ◽  
pp. G1494-G1501 ◽  
Author(s):  
Scott D. Smid ◽  
Richard L. Young ◽  
Nicole J. Cooper ◽  
L. Ashley Blackshaw
Keyword(s):  
Vagal Afferents ◽  
Gastric Distension ◽  
Response Curves ◽  
Proximal Stomach ◽  
Receptor Agonists ◽  
Nodose Ganglia ◽  
Afferent Fibers ◽  
Before And After ◽  
Vagal Afferent

GABAB-receptor (GABABR) agonists reduce transient lower esophageal sphincter relaxation (TLESR) and reflux episodes through an action on vagal pathways. In this study, we determined whether GABABR are expressed on vagal afferent neurones and whether they modulate distension-evoked discharge of vagal afferents in the isolated stomach. Vagal mehanoreceptor activity was recorded following distensions of the isolated ferret proximal stomach before and after perfusion with the GABABR-selective agonists baclofen and 3-aminopropylphosphinic acid (3-APPiA). Retrograde labeling and immunohistochemistry were used to identify GABABR located on vagal afferent neurones in the nodose ganglia. Vagal afferent fibers responded to isovolumetric gastric distension with an increase in discharge. The GABAB-receptor agonists baclofen (5 × 10−5 M) and 3-APPiA (10−6 to 10−5 M) but not muscimol (GABAA-selective agonist: 1.3 × 10−5 M) significantly decreased afferent distension-response curves. The effect of baclofen (5 × 10−5 M) was reversed by the GABAB-receptor antagonist CGP 62349 (10−5 M). Over 93% of retrogradely labeled gastric vagal afferents in the nodose ganglia expressed immunoreactivity for the GABABR. GABABR expressed on vagal afferent fibers directly inhibit gastric mechanosensory activity. This is likely a contributing mechanism to the efficacy of GABAB-receptor agonists in reducing TLESR and reflux episodes in vivo.

Vagally mediated, nonparacrine effects of cholecystokinin-8s on rat pancreatic exocrine secretion

2007 ◽  
Vol 293 (2) ◽  
pp. G493-G500 ◽  
Author(s):  
Eddy Viard ◽  
Zhongling Zheng ◽  
Shuxia Wan ◽  
R. Alberto Travagli
Keyword(s):  
Brain Stem ◽  
Protein Secretion ◽  
Exocrine Secretion ◽  
Vagal Afferents ◽  
Dependent Manner ◽  
Pancreatic Exocrine Secretion ◽  
Sprague Dawley ◽  
Pancreatic Exocrine ◽  
Vagal Afferent

Cholecystokinin (CCK) has been proposed to act in a vagally dependent manner to increase pancreatic exocrine secretion via actions exclusively at peripheral vagal afferent fibers. Recent evidence, however, suggests the CCK-8s may also affect brain stem structures directly. We used an in vivo preparation with the aims of 1) investigating whether the actions of intraduodenal casein perfusion to increase pancreatic protein secretion also involved direct actions of CCK at the level of the brain stem and, if so, 2) determining whether, in the absence of vagal afferent inputs, CCK-8s applied to the dorsal vagal complex (DVC) can also modulate pancreatic exocrine secretion (PES). Sprague-Dawley rats (250–400 g) were anesthetized and the common bile-pancreatic duct was cannulated to collect PES. Both vagal deafferentation and pretreatment with the CCK-A antagonist lorglumide on the floor of the fourth ventricle decreased the casein-induced increase in PES output. CCK-8s microinjection (450 pmol) in the DVC significantly increased PES; the increase was larger when CCK-8s was injected in the left side of the DVC. Protein secretion returned to baseline levels within 30 min. Microinjection of CCK-8s increased PES (although to a lower extent) also in rats that underwent complete vagal deafferentation. These data indicate that, as well as activating peripheral vagal afferents, CCK-8s increases pancreatic exocrine secretion via an action in the DVC. Our data suggest that the CCK-8s-induced increases in PES are due mainly to a paracrine effect of CCK; however, a relevant portion of the effects of CCK is due also to an effect of the peptide on brain stem vagal circuits.

scholarly journals Gentle Manual Acupuncture Could Better Regulate Gastric Motility and Vagal Afferent Nerve Discharge of Rats with Gastric Hypomotility

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yangyang Liu ◽  
Yang Bai ◽  
Yue Pan ◽  
Zhifang Xu ◽  
Yuxin Fang ◽  
...  
Keyword(s):  
Gastric Motility ◽  
Underlying Mechanism ◽  
Afferent Nerve ◽  
Manual Acupuncture ◽  
Intensity Effect ◽  
Afferent Nerves ◽  
Strong Stimulation ◽  
Vagal Afferent ◽  
Acupuncture Effects ◽  
Nerve Discharge

The variation of stimulus intensity of manual acupuncture (MA) may produce diverse acupuncture effects. However, the intensity-effect relationship and the underlying mechanism of MA are still elusive. In this study, the effects of MA regulation of gastric motility were investigated after lifting-thrusting MA treatment with four different frequencies (1 Hz, 2 Hz, 3 Hz, and 4 Hz) at ST36. The experiments were conducted on rats with gastric hypomotility caused by atropine. The results showed that the gastric motility amplitude decreased after atropine injection, while the treatment of four types of MA affected the gastric motility amplitude in varying degrees. Specifically, 2 Hz MA exhibited the most effective results, while 4 Hz MA had the least effect; the effects of 1 Hz MA and 3 Hz MA were between the effects induced with 2 Hz and 4 Hz. Furthermore, the response of gastric vagal afferent nerve discharge and gastric motility was examined after MA treatment with frequencies of 2 Hz and 4 Hz, respectively, on ST36 in order to elucidate the mechanism of MA regulation of gastric motility. The results showed that 2 Hz MA was able to increase the amplitude of gastric motility and discharge frequency of gastric vagal afferent nerves, while 4 Hz MA exhibited seldom effects. These findings suggest that gentle MA (2 Hz) has more stimulating effects than strong stimulation with MA (4 Hz) on gastric hypomotility. In addition, gastric motility regulated by MA was associated with vagal afferent nerve activation.

scholarly journals Regulation of Calcineurin through Transcriptional Induction of the calcineurin Aβ Promoter In Vitro and In Vivo

2005 ◽  
Vol 25 (15) ◽  
pp. 6649-6659 ◽  
Author(s):  
Toru Oka ◽  
Yan-Shan Dai ◽  
Jeffery D. Molkentin
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Pressure Overload ◽  
Growth Stimulation ◽  
Feedback Mechanism ◽  
Activated T Cells ◽  
The Central Nervous System ◽  
Positive Feedback Mechanism ◽  
Transcriptional Induction

ABSTRACT The calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway has been shown to be of critical importance in regulating the growth response of cardiac myocytes. We have previously demonstrated that calcineurin Aβ (CnAβ) mRNA and protein are increased in response to growth stimulation, although the precise regulatory mechanism underlying CnAβ upregulation is not clear. Here, we isolated the mouse CnAβ promoter and characterized its responsiveness to growth stimuli in vitro and in vivo. A 2.3-kb promoter fragment was strongly activated by phenylephrine and endothelin-1 stimulation and by cotransfection with constitutively active CnA, NFATc4, and GATA4. Using chromatin immunoprecipitation, sequence regions were identified within the 2.3-kb promoter that associated with NFAT and GATA4, as well as with acetylated histone H3, following agonist stimulation. Consistent with the chromatin immunoprecipitation experiments, deletion of the distal half of the CnAβ promoter severely reduced NFAT, GATA4, and hypertrophic agonist-mediated activation. To investigate in vivo activity, we generated β-galactosidase (LacZ) containing transgenic mice under the control of the CnAβ 2.3-kb promoter. CnAβ-LacZ mice showed expression in the heart that was cyclosporine sensitive, as well as expression in the central nervous system and skeletal muscle from early embryonic stages through adulthood. CnAβ-LacZ mice were subjected to cardiac pressure overload stimulation and crossbreeding with mice containing cardiac-specific transgenes for activated calcineurin and NFATc4, which revealed inducible expression in the heart. These results indicate that the CnAβ 2.3-kb promoter is specifically activated by hypertrophic stimuli through a positive feedback mechanism involving NFAT and GATA4 transcription factors, suggesting transcriptional induction of CnAβ expression as an additional means of regulating calcineurin activity in the heart.

Enhancement of antral contractions and vagal afferent signaling with synchronized electrical stimulation

2003 ◽  
Vol 285 (3) ◽  
pp. G577-G585 ◽  
Author(s):  
Shachar Peles ◽  
Jaime Petersen ◽  
Ricardo Aviv ◽  
Shai Policker ◽  
Ossama Abu-Hatoum ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Vagal Afferents ◽  
Mechanical Stimuli ◽  
The Central Nervous System ◽  
Rhythmic Firing ◽  
Vagal Afferent ◽  
Electrically Enhanced ◽  
Smooth Muscle Contractions ◽  
Afferent Signaling ◽  
Antral Distension

Gastric filling activates vagal afferents involved in peripheral signaling to the central nervous system (CNS) for food intake. It is not known whether these afferents linearly encode increasing contractions of the antrum during antral distension (AD). The aim of this study was to investigate effects of AD and electrically enhanced antral contractions on responses of vagal afferents innervating the antrum. Single-fiber recordings were made from the vagal afferents in anesthetized male Long-Evans rats. Antral contractions were measured with a solid-state probe placed in the antrum. A nonexcitatory electrical stimulation (NES) inducing no smooth muscle contractions was applied during the ascending phase of antral contractions to enhance subsequent antral contractions. Fifty-six fibers identified during AD (1 ml for 30 s) were studied through different types of mechanical stimuli. Under normal conditions, one group of fibers exhibited rhythmic firing in phase with antral contractions. Another group of fibers had nonrhythmic spontaneous firing. Responses of 15 fibers were tested with NES during multiple-step distension (MSD). NES produced a mean increase in antral contraction amplitude (177.1 ± 35.3%) and vagal afferent firing (21.6 ± 2.6%). Results show that both passive distension and enhanced antral contractions activate distension-sensitive vagal afferents. Responses of these fibers increase linearly to enhanced antral contraction induced by NES or MSD up to a distending volume of 0.6 ml. However, responses reached a plateau at a distending volume >0.8 ml. We concluded that enhanced contraction of the antrum can activate vagal afferents signaling to the CNS.

Mediation by the central nervous system is critical to the in vivo activity of the GH secretagogue L-692,585

1996 ◽  
Vol 148 (2) ◽  
pp. 371-380 ◽  
Author(s):  
G J Hickey ◽  
J Drisko ◽  
T Faidley ◽  
C Chang ◽  
L L Anderson ◽  
...  
Keyword(s):  
Intact Animal ◽  
Control Group ◽  
Cortisol Response ◽  
Gh Secretion ◽  
Significant Difference ◽  
Before And After ◽  
The Central Nervous System ◽  
Cortisol Responses ◽  
Inhibitory Tone

Abstract To investigate the effect of hypophyseal transection (HST) on GH secretagogue activity of the non-peptidyl GH secretagogue L-692,585 in the conscious pig, male castrated swine were randomly assigned to either a hypophyseal stalk transection group (HST; n=3) or to a sham-operated control group (SOC; n=3). Treatments administered were L-692,585 (100 γg/kg), human GH-releasing factor(1–29)NH2 (GRF; 20 γg/kg) or L-692,585 (100 γg/kg) + GRF (20 γg/kg) on days −7 to −3 before surgery and days +3 to +8 after surgery. To evaluate the integrity of the pituitary gland, the animals were challenged with corticotropin-releasing hormone (CRH; 150 γg) or GnRH (150 ng/kg) both before and after surgery. Blood was collected from −60 to +180 min post treatment and assayed for GH, cortisol and LH. Before surgery, no significant difference (P>0·05) in peak GH response (ng/ml) was present between the two groups (SOC vs HST) in response to L-692,585 (101 ± 12 vs 71 ± 9) or L-692,585 + GRF (171 ± 21 vs 174 ± 21). Only two out of three SOC vs three out of three HST pigs responded to GRF (13 ± 2 vs 25 ± 3) resulting in a significant difference between groups. Following surgery, significant differences were present in peak GH response (ng/ml) between SOC and HST groups following L-692,585 (79 ± 6 vs 13·8 ± 1·0); however, the response to L-692,585 + GRF was similar (115 ± 8 vs 94 ± 7). All animals responded to GRF; however, a significant difference was present between groups due to the magnitude of the responses. Whereas the cortisol responses (ng/ml) to L-692,585 in the SOC and HST groups were similar before surgery, a significant difference was present after surgery (44·4 ± 6·4 vs 14·6 ± 2·1). No significant difference was noted between the HST and SOC groups in response to CRH or GnRH either before or after surgery. These results indicated that L-692,585 induced an immediate GH response in the intact animal in contrast to GRF where the GH release was variable. L-692,585 also stimulated an immediate increase in cortisol levels. Transection of the hypophyseal stalk dramatically decreased but did not ablate the GH or cortisol response to L-692,585. Co-administration of L-692,585 + GRF induced an immediate GH response of similar magnitude in the intact and HST animal. We conclude that L-692,585 has a direct but limited action at the level of the pituitary and that an intact hypophyseal stalk is required for a maximal GH and cortisol response. L-692,585 acts with GRF at the level of the pituitary to induce a maximal GH response. These findings suggest that L-692,585 stimulates GH secretion by acting in combination with GRF and interrupting the inhibitory tone of somatostatin on the somatotroph. Journal of Endocrinology (1996) 148, 371–380

scholarly journals Kinetic modelling of [11C]PBR28 for 18 kDa translocator protein PET data: A validation study of vascular modelling in the brain using XBD173 and tissue analysis

2017 ◽  
Vol 38 (7) ◽  
pp. 1227-1242 ◽  
Author(s):  
Mattia Veronese ◽  
Tiago Reis Marques ◽  
Peter S Bloomfield ◽  
Gaia Rizzo ◽  
Nisha Singh ◽  
...  
Keyword(s):  
Kinetic Modelling ◽  
Translocator Protein ◽  
Heterogeneous Distribution ◽  
Positron Emission ◽  
Before And After ◽  
Histological Data ◽  
The Central Nervous System ◽  
Specific Tissue ◽  
Pet Scans

The 18 kDa translocator protein (TSPO) is a marker of microglia activation in the central nervous system and represents the main target of radiotracers for the in vivo quantification of neuroinflammation with positron emission tomography (PET). TSPO PET is methodologically challenging given the heterogeneous distribution of TSPO in blood and brain. Our previous studies with the TSPO tracers [11C]PBR28 and [11C]PK11195 demonstrated that a model accounting for TSPO binding to the endothelium improves the quantification of PET data. Here, we performed a validation of the kinetic model with the additional endothelial compartment through a displacement study. Seven subjects with schizophrenia, all high-affinity binders, underwent two [11C]PBR28 PET scans before and after oral administration of 90 mg of the TSPO ligand XBD173. The addition of the endothelial component provided a signal compartmentalization much more consistent with the underlying biology, as only in this model, the blocking study produced the expected reduction in the tracer concentration of the specific tissue compartment, whereas the non-displaceable compartment remained unchanged. In addition, we also studied TSPO expression in vessels using 3D reconstructions of histological data of frontal lobe and cerebellum, demonstrating that TSPO positive vessels account for 30% of the vascular volume in cortical and white matter.

Secretin inhibits vagal afferent nerve discharge in response to gastric distension in rats

2000 ◽  
Vol 118 (4) ◽  
pp. A840
Author(s):  
Je Lu ◽  
Zong-Seng Huang ◽  
James P. Li ◽  
Ying Zhao ◽  
William Y. Chey
Keyword(s):  
Afferent Nerve ◽  
Gastric Distension ◽  
Vagal Afferent ◽  
Nerve Discharge

Effects of bilateral vagal cold block on vasopressin in conscious dogs

1984 ◽  
Vol 246 (4) ◽  
pp. R566-R569
Author(s):  
V. S. Bishop ◽  
M. D. Thames ◽  
P. G. Schmid
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Arginine Vasopressin ◽  
Afferent Nerve ◽  
Vagal Afferents ◽  
Inhibitory Influence ◽  
Conscious Dog ◽  
Afferent Nerves ◽  
Vagal Afferent ◽  
Plasma Arginine

Bilateral vagal cold block was used to interrupt afferent nerve traffic in the cervical vagi and thus to determine the tonic inhibitory influence of vagal afferents on plasma arginine vasopressin (AVP) concentrations in the conscious dog. Experiments were performed in conscious aortic baroreceptor-denervated dogs with carotid baroreflexes intact or with sinoaortic denervation. In the presence of intact carotid baroreflexes (n = 11) vagal cold block significantly increased arterial pressure (99 +/- 5 to 120 +/- 8 mmHg), heart rate (98 +/- 2 to 168 +/- 11 beats/min), and AVP (2.9 +/- 0.6 to 6.7 +/- 1.3 microU/ml). Chronic sinoaortic denervation did not significantly alter plasma AVP (4.4 +/- 1.0 microU/ml). However, vagal cold block in these totally denervated animals caused a significantly greater increase in arterial pressure (116 +/- 7 to 167 +/- 7 mmHg) and plasma AVP (4.4 +/- 1 to 33.4 +/- 4.8 microU/ml) compared with the responses observed in dogs with intact carotid baroreflexes. These results indicate that vagal afferent nerves exert a significant tonic inhibitory influence on the secretion of AVP in the conscious aortic baroreceptor-denervated dogs as well as in dogs with sinoaortic denervation.

scholarly journals In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury

2019 ◽  
Vol 116 (33) ◽  
pp. 16603-16612 ◽  
Author(s):  
Eric B. Miller ◽  
Pengfei Zhang ◽  
Karli Ching ◽  
Edward N. Pugh ◽  
Marie E. Burns
Keyword(s):  
Adaptive Optics ◽  
Time Behavior ◽  
Scanning Laser Ophthalmoscopy ◽  
Local Damage ◽  
Mechanistic Studies ◽  
Neuronal Function ◽  
Tight Cluster ◽  
Before And After ◽  
The Central Nervous System

Microglia respond to damage and microenvironmental changes within the central nervous system by morphologically transforming and migrating to the lesion, but the real-time behavior of populations of these resident immune cells and the neurons they support have seldom been observed simultaneously. Here, we have used in vivo high-resolution optical coherence tomography (OCT) and scanning laser ophthalmoscopy with and without adaptive optics to quantify the 3D distribution and dynamics of microglia in the living retina before and after local damage to photoreceptors. Following photoreceptor injury, microglia migrated both laterally and vertically through the retina over many hours, forming a tight cluster within the area of visible damage that resolved over 2 wk. In vivo OCT optophysiological assessment revealed that the photoreceptors occupying the damaged region lost all light-driven signaling during the period of microglia recruitment. Remarkably, photoreceptors recovered function to near-baseline levels after the microglia had departed the injury locus. These results demonstrate the spatiotemporal dynamics of microglia engagement and restoration of neuronal function during tissue remodeling and highlight the need for mechanistic studies that consider the temporal and structural dynamics of neuron–microglia interactions in vivo.

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