Functional alterations in jejunal myenteric neurons during inflammation in nematode-infected guinea pigs

1998 ◽  
Vol 275 (5) ◽  
pp. G922-G935 ◽  
Author(s):  
Jeffrey M. Palmer ◽  
Margaret Wong-Riley ◽  
Keith A. Sharkey

Intracellular recordings of jejunal myenteric neurons with an afterspike hyperpolarization (AH) from Trichinella spiralis-infected animals showed enhanced excitability on days 3, 6, and 10postinfection (PI) compared with uninfected animals. Lower membrane potential, increased membrane input resistance, decreased threshold for action potential discharge, decreased AH amplitude and duration, and increased fast excitatory postsynaptic potential amplitude and duration were characteristic of neuronal recordings from infected animals. Concurrent with electrophysiological changes during T. spiralis infection, increased cytochrome oxidase activity, a marker of neuronal metabolic activity, and the expression of nuclear c-Fos immunoreactivity, an indicator of transcriptional-translational activity, were also observed in myenteric ganglion cells. Double-labeling for calbindin-immunoreactive myenteric neurons revealed that ∼50% of these neurons also expressed increased c-Fos immunoreactivity during T. spiralis infection. Myeloperoxidase activity was significantly higher in the jejunum of T. spiralis-infected guinea pigs on days 3, 6, and 10 PI vs. uninfected counterparts. The expression of c-Fos in calbindin-immunoreactive neurons together with enhanced neuronal electrical and metabolic activity during nematode-induced intestinal inflammation suggests the onset of excitation-transcription coupled changes in enteric neural microcircuits.

1992 ◽  
Vol 263 (6) ◽  
pp. G838-G846 ◽  
Author(s):  
J. F. Tack ◽  
J. Janssens ◽  
G. Vantrappen ◽  
J. D. Wood

Intracellular recording methods were used to study the actions of 5-hydroxytryptamine (5-HT) on 257 myenteric neurons in the guinea pig gastric antrum. Application of 5-HT caused three types of postsynaptic responses. A fast-activating depolarizing response was accompanied by a decreased input resistance and desensitized quickly to repeated applications. It was mediated by a 5-HT3 receptor. A slowly activating depolarization, accompanied by an increase in the input resistance and enhancement of the excitability, was mainly observed in after hyperpolarizing/type 2 neurons. It was suppressed by the prokinetic benzamide compound renzapride, while classical 5-HT1-4 receptor antagonists had no effect, suggesting the involvement of a 5-HT1p receptor as described in small intestinal neurons. A long-lasting hyperpolarizing response, accompanied by a decreased input resistance, was observed in a small subset of neurons. This response seemed to be mediated by a 5-HT1a receptor. Superfusion of 5-HT caused a dose-dependent inhibition of the stimulus-evoked nicotinic cholinergic fast excitatory postsynaptic potential (EPSP), which was mediated by a presynaptic 5-HT1a receptor. 5-HT also presynaptically inhibited the slow EPSP.


2000 ◽  
Vol 278 (1) ◽  
pp. R118-R124 ◽  
Author(s):  
Constance J. Faro ◽  
Roger D. Reidelberger ◽  
Jeffrey M. Palmer

Our aim was to investigate the cause-effect relationship between intestinal inflammation induced by infection with enteric stages of Trichinella spiralis and decreased host food intake. A suppression of food intake in T. spiralis-infected rats occurred within the first 24 h postinfection (PI) and was maximized by day 6 PI. Food intake, cumulated over an 8-day PI period, decreased by 59% compared with uninfected animals. The anti-inflammatory glucocorticoid betamethasone 21-phosphate was orally administered to rats in their drinking water to suppress T. spiralis-induced jejunal inflammation. When treated with a low dose of glucocorticoid (5.2 μg/ml), food intake in infected rats was still significantly reduced, but only by 21% compared with glucocorticoid-treated, uninfected rats. At the highest glucocorticoid dose (10.4 μg/ml) administered, infection-induced reduction in food intake was not different from that of glucocorticoid-treated, uninfected counterparts. The elevation in jejunal myeloperoxidase activity caused by infection was also significantly blunted by oral glucocorticoid treatment. Our results suggest that suppressed host food intake during enteric T. spiralis infection is directly linked to intestinal inflammation.


1971 ◽  
Vol 177 (1049) ◽  
pp. 509-539 ◽  

Synaptic transmission has been analysed in parasympathetic nerve cells that lie in the transparent interatrial septum of the heart of the frog. Using Nomarski interference optics, one can see much cellular detail, including synaptic boutons in living preparations. 1. On each ganglion cell, the 10 to 20 synaptic boutons are usually derived from a single vagal nerve fibre. These fibres branch extensively to innervate a number of septal ganglion cells. 2. The chemical transmitter, acetylcholine (ACh), liberated by a presynaptic impulse survives for up to 40 ms, setting up an excitatory postsynaptic potential (e.p.s.p.) which triggers one and sometimes two action potentials in the postsynaptic cell. The e.p.s.p. is made up of quantal components, as at the neuromuscular junction. 3. Nerve-evoked e.p.s.p.s can be well matched in amplitude and time course by iontophoretic application of ACh to selected areas of the neuronal membrane. In particular, the miniature e.p.s.p., which is due to the focal release of a small quantity of transmitter, was accurately mimicked by iontophoretic application of ACh. By grading the amount of ACh released from an electrode one could also duplicate the wide variety of nerve-evoked postsynaptic discharges of ganglion cells. 4. The permeability changes initiated in the postsynaptic membrane by applied ACh and the synaptic transmitter appear identical, since the ionic fluxes for both responses have the same equilibrium potential. Also, the receptors which react with the synaptic transmitter are desensitized by applied ACh. 5. Cholinesterase inhibitors (Tensilon and Eserine) have a variable action on different cells, with respect both to nerve-evoked and Ach evoked potentials. The reasons for this variation are unclear, and need further study. 6. Miniature e.p.s.p.s resemble analogous potentials at nerve-muscle junctions and other synapses. A significant proportion of the min e.p.s.p.s is released as multiple units. This proportion is increased in high Ca2+, while single units alone occur in a low Ca2+-high Mg2+ environment. 7. The experiments provide information about the release of ACh from nerve terminals and its action on the postsynaptic membrane of neurons. They are in good agreement with analogous studies on skeletal neuromuscular junctions


1977 ◽  
Vol 6 (3) ◽  
pp. 274-279
Author(s):  
Omar O. Barriga

Six diethylaminoethyl-cellulose fractions of a larval Trichinella spiralis extract, an Ascaris suum extract, and a nonrelated protein were used for cutaneous tests in guinea pigs with 8-, 14-, and 73-day-old T. spiralis infections, in guinea pigs with 13-day-old A. suum infections, and in normal guinea pigs. A selected T. spiralis fraction was used in hemagglutination (HA) tests with sera of 8 T. spiralis -infected rabbits, 41 sera of trichinellosis patients positive by bentonite agglutination tests, and 50 sera of clinically healthy persons. Immediate-type cutaneous reactions revealed extensive cross-reactivity between both parasites, although the establishment of conventional limits for considering a reaction positive allowed the specific diagnosis of acute or chronic trichinellosis with different fractions. Delayed-type reactions were specific with all fractions except one, and different fractions reacted during either the acute or the chronic phase of trichinellosis. HA detected anti- Trichinella antibodies in all the rabbits 9 to 10 days postinfection, in all trichinellosis patients, and in none of the healthy people. Correlation between HA and bentonite agglutination titers and other considerations suggest that HA with the selected fraction detects early antibodies. HA inhibition tests with A. suum extract suggest lack of HA cross-reactivity between the A. suum - and T. spiralis -selected fractions. The use of different fractions in diverse tests for clinical or epidemiological studies is suggested.


2000 ◽  
Vol 279 (3) ◽  
pp. G543-G551 ◽  
Author(s):  
D. Torrents ◽  
P. Vergara

Functional motor changes and morphological alterations have been associated with intestinal inflammation. The aim of our study was to evaluate functional alterations of intestinal reflexes and of the responses to CCK in the Trichinella spiralis model of intestinal inflammation. Rats were prepared with strain gauges and electrodes in the small intestine to evaluate spontaneous motor activity, the ascending contraction of the peristaltic reflex, and the motor responses to CCK-8 infusion. Infected animals showed increased motor activity at the duodenum and jejunum but not at the ileum. Ascending contraction was increased in both duodenum and ileum. Ascending excitation after Nω-nitro-l-arginine was still increased as well as the residual response after atropine. Response to CCK-8 during intestinal inflammation was changed in the jejunum, in which it turned from the inhibition shown in healthy animals to excitation. NADPH-diaphorase staining did not show any changes between distribution and density of positive neurons in either healthy or infected animals. In conclusion, intestinal inflammation induces functional changes in the motor activity that could explain the abnormal motor responses observed in inflammatory disorders.


2018 ◽  
Vol 19 (12) ◽  
pp. 4016 ◽  
Author(s):  
Valéria da Silva ◽  
Aurigena de Araújo ◽  
Daline Araújo ◽  
Maíra Lima ◽  
Roseane Vasconcelos ◽  
...  

Inflammatory bowel disease is triggered by an uncontrolled immune response associated with genetic, environmental, and intestinal microbiota imbalance. Ipomoea asarifolia (IA), popularly known as “salsa” or “brave salsa”, belongs to the Convolvulaceae family. The aim of this approach was to study the preventive effect of IA aqueous extract in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Rats pretreated with IA extract or sulfasalazine (SSZ) received intracolonic instillation of DNBS in 50% ethanol (v/v). IA extract presented a protective effect against intestinal inflammation, with improvement in the disease activity index and macroscopic damage. IA or SSZ significantly reduced myeloperoxidase activity, and also down-regulation of the gene expression of JNK1, NF-κβ-p65, STAT3, and decreased levels of TNFα, IL-1β, and increased IL-10, associated with a significant improvement of oxidative stress, in addition to a reduction in MDA and an increase of glutathione in colonic tissue. The protective effect of the extract was also confirmed in histological evaluation, showing preservation of the colonic cytoarchitecture. Immunohistochemical analysis revealed down-regulation of NF-κβ-p65, iNOS, IL-17, and up-regulation of SOCs-1 and MUC-2. IA extract presents antioxidant and anti-inflammatory intestinal properties, and proved to be a potential application for preventing damage induced by DNBS.


1997 ◽  
Vol 77 (5) ◽  
pp. 2605-2615 ◽  
Author(s):  
John B. Munson ◽  
Robert C. Foehring ◽  
Lorne M. Mendell ◽  
Tessa Gordon

Munson, John B., Robert C. Foehring, Lorne M. Mendell, and Tessa Gordon. Fast-to-slow conversion following chronic low-frequency activation of medial gastrocnemius muscle in cats. II. Motoneuron properties. J. Neurophysiol. 77: 2605–2615, 1997. Chronic stimulation (for 2–3 mo) of the medial gastrocnemius (MG) muscle nerve by indwelling electrodes renders the normally heterogeneous MG muscle mechanically and histochemically slow (type SO). We tested the hypothesis that motoneurons of MG muscle thus made type SO by chronic stimulation would also convert to slow phenotype. Properties of all single muscle units became homogeneously type SO (slowly contracting, nonfatiguing, nonsagging contraction during tetanic activation). Motoneuron electrical properties were also modified in the direction of type S, fatigue-resistant motor units. Two separate populations were identified (on the basis of afterhyperpolarization, rheobase, and input resistance) that likely correspond to motoneurons that had been fast (type F) or type S before stimulation. Type F motoneurons, although modified by chronic stimulation, were not converted to the type S phenotype, despite apparent complete conversion of their muscle units to the slow oxidative type (type SO). Muscle units of the former type F motor units were faster and/or more powerful than those of the former type S motor units, indicating some intrinsic regulation of motor unit properties. Experiments in which chronic stimulation was applied to the MG nerve cross-regenerated into skin yielded changes in motoneuron properties similar to those above, suggesting that muscle was not essential for the effects observed. Modulation of group Ia excitatory postsynaptic potential (EPSP) amplitude during high-frequency trains, which in normal MG motoneurons can be either positive or negative, was negative in 48 of 49 chronically stimulated motoneurons. Negative modulation is characteristic of EPSPs in motoneurons of most fatigue-resistant motor units. The general hypothesis of a periphery-to-motoneuron retrograde mechanism was supported, although the degree of control exerted by the periphery may vary: natural type SO muscle appears especially competent to modify motoneuron properties. We speculate that activity-dependent regulation of the neurotrophin-(NT) 4/5 in muscle plays an important role in controlling muscle and motoneuron properties.


1993 ◽  
Vol 264 (3) ◽  
pp. G414-G421 ◽  
Author(s):  
F. L. Christofi ◽  
J. D. Wood

Intracellular microelectrodes were used to examine the actions of pituitary adenylate cyclase-activating peptide (PACAP) on morphologically identified myenteric neurons and glial cells of the guinea pig small bowel. PACAP-27 and PACAP-38 evoked excitatory responses in 96% of after hyperpolarizing (AH)/type 2 neurons. The half-maximal concentration for PACAP-27 was 1.5 nM. The responses consisted of membrane depolarization in association with increased input resistance, suppression of hyperpolarizing afterpotentials, and repetitive spike discharge. Forskolin mimicked the action of PACAP in all AH/type 2 neurons. PACAP excited 36% of S/type 1 neurons. Most of the AH/type 2 neurons had Dogiel II morphology, whereas the S/type 1 neurons were uniaxonal with morphology characteristics of Dogiel I or filamentous neurons. No glial cells responded to PACAP. A selective A1 adenosine receptor agonist blocked the excitatory action of PACAP, and this was reversed by a selective A1 antagonist. The results suggest that excitatory PACAP receptors and inhibitory adenosine A1 receptors are linked to adenylate cyclase in AH/type 2 myenteric neurons.


1994 ◽  
Vol 72 (5) ◽  
pp. 2438-2450 ◽  
Author(s):  
R. W. Rhoades ◽  
C. A. Bennett-Clarke ◽  
M. Y. Shi ◽  
R. D. Mooney

1. Recent immunocytochemical and receptor binding data have demonstrated a transient somatotopic patterning of serotonin (5-HT)-immunoreactive fibers in the primary somatosensory cortex of developing rats and a transient expression of 5-HT1B receptors on thalamocortical axons from the ventral posteromedial thalamic nucleus (VPM). 2. These results suggest that 5-HT should strongly modulate thalamocortical synaptic transmission for a limited time during postnatal development. This hypothesis was tested in intracellular recording experiments carried out in thalamocortical slice preparations that included VPM, the thalamic radiations, and the primary somatosensory cortex. Effects of 5-HT and analogues were monitored on membrane potentials and input resistances of cortical neurons and on the amplitude of the synaptic potentials evoked in them by stimulation of VPM. 3. Results obtained from cortical neurons in slices taken from rats during the first 2 wk of life indicated that 5-HT strongly inhibited the VPM-evoked excitatory postsynaptic potential (EPSP) recorded from cortical neurons in a dose-dependent manner. In contrast, 5-HT had no significant effects on membrane potential, input resistance, or depolarizations induced by direct application of glutamic acid to cortical cells. 4. The effects of 5-HT were mimicked by the 5-HT1B receptor agonists 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) and 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]-quinoxaline maleate and antagonized by the 5-HT1B receptor antagonist (-)-pindolol. The 5-HT1A agonist [(+/-)8-hydroxydipropylaminotetralin HBr] (8-OH-DPAT) had less effect on the VPM-elicited EPSP, and the effects of 5-HT upon this response were generally not antagonized by either 1-(2-methoxyphenyl)-4-[4-(2- phthalimmido)butyl]piperazine HBr (a 5-HT1A antagonist) or ketanserine (a 5-HT2 antagonist) or spiperone (a 5-HT1A and 2 antagonist). 5. The ability of 5-HT to inhibit the VPM-evoked EPSP in cortical neurons was significantly reduced in slices from animals > 2 wk of age. The effectiveness of TFMPP in such animals was even more attenuated than that of 5-HT, and the effectiveness of 8-OH-DPAT was unchanged with age. These results are consistent with the disappearance of 5-HT1B receptors from thalamocortical axons after the second postnatal week and the maintenance of 5-HT1A receptors on some neurons. 6. All of the results obtained in this study are consistent with the conclusion that 5-HT has a profound, but developmentally transient, presynaptic inhibitory effect upon thalamocortical transmission in the rat's somatosensory cortex.


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