Nippostrongylus brasiliensisinfection evokes neuronal abnormalities and alterations in neurally regulated electrolyte transport in rat jejunum

Abstract

Neuronal abnormalities have been described in the intestine of helminth-infected rats. However, the physiological ramifications of these changes have not been determined. Here, we examined epithelial ion secretion, indicated by increases in short-circuit current (Isc), evoked by electrical transmural stimulation (TS) of enteric nerves in Ussing-chambered jejunal tissues from Nippostrongylus brasiliensis-infected rats. Rats were examined at 10 and 35 days post-infection (p.i.); non-infected rats served as controls. TS resulted in significantly reduced ion secretion in jejunum from 10 day p.i. rats compared to controls or jejunum from 35 day p.i. rats. The TS response in tissue from infected rats had, unlike controls, no cholinergic component. Tissues from both non-infected and infected rats were equally responsive to the muscarinic agonist bethanechol, suggesting that the cholinergic defect was neuronal and not an inability of the epithelium to respond to cholinergic stimulation. However, increases in Isc evoked by exogenous substance P (SP) in tissue from rats 10 day p.i. were reduced in magnitude to approximately 25% of control values. Concomitant with these physiological changes, tissue from infected rats contained increased amounts of substance P immunoreactivity and intestinal sections displayed increased numbers of substance P-immunoreactive nerve fibre profiles at both 10 and 35 days p.i. Thus, following N. brasiliensis infection there is a shift in the enteric nervous system away from cholinergic to non-cholinergic regulation, associated with increased amounts of the pro-inflammatory neuropeptide, substance P. We speculate that changes in neuronal structure and function are intimately involved in the co-ordinated multicellular response to intestinal parasitic infection and subsequent gut recovery.

Enteric Nematodes Induce Stereotypic STAT6-Dependent Alterations in Intestinal Epithelial Cell Function

“…The reduced acetylcholine responses, however, were STAT6 dependent, indicating that this inhibitory response requires activation of both IL-4 and IL-13 signaling pathways and suggesting that the effect is downstream of STAT6. Although negative effects of worm infection on neurally mediated epithelial secretion do not promote rapid worm clearance, they do prevent fluid loss through diarrhea (27,28). In the present study diarrhea was not a consequence of infection with any of the three nematodes.…”

Implications of Tachykinins and Calcitonin Gene-Related Peptide in Inflammatory Bowel Disease

“…6). Thus, nerve remodelling and a shift in the enteric nervous system away from cholinergic to peptidergic regulation takes place in experimental infection and inflammation of the intestine [60,107]. In accordance with this scheme ( fig.…”

Neuropeptides and Neurogenic Mechanisms in Oral and Periodontal Inflammation

“…Changes in peptidergic neurons leading to imbalances in neuropeptide expression are believed to be intimately associated with gastrointestinal disease. Alterations in peptidergic innervation of the gut have been associated with gastrointestinal infection (Masson et al, 1996) and inflammation (Kimura et al, 1994). Further evidence supporting a neurogenic involvement in gut inflammation comes from studies showing positive responses to neuropeptide antagonist treatment (Croci et al, 1997).…”