Neuronal activation and plasticity in Schistosoma mansoni infected mice

Abstract

Schistosomiasis leads to structural and functional changes which may result from unbalanced release of some inflammatory mediators. The aim of the study was to investigate the effect of intestinal parasitic infection on nitric oxide release and to evaluate the neural plasticity that leads to motility disturbance. Experiments were performed in Swiss mice 8- and 12-weeks following infection with Schistosoma mansoni compared to untreated controls. Jejunal motility was assessed using a Trendelenburg preparation to study aboral directed peristaltic pressure waves. Histological examination was used to determine the pathological characteristics of inflammation. Parasitic infection produces diffuse inflammatory infiltrate in both 8- and 12-weeks infected animals. Inflammation had significant effect on peristaltic pressure waves amplitude and intervals at 8-weeks compared to control; whereas, in 12-weeks post infection there was a significant decrease in peristaltic pressure waves amplitude and interval compared to 8- weeks and control. Nitric oxide synthase inhibitor (L-NAME 100 μM) induced a significant increase in amplitude and decrease in intervals in control, 8- and 12- weeks infected animals. In conclusion, parasitic infection leads to disturbance in the release of the inflammatory mediators. This study indicated the role of nitric oxide in developing granulomatous inflammation and participating in motility disturbance.

Keywords: Inflammatory mediators; Intestinal motility; Mice; Nitric oxide; Schistosoma mansoni.

Figure 1

Cross sections of the jejunum from (A) control mice and from mice that were infected with S. mansoni for (B) 8- and (C) 12-weeks. The jejunum of 8-weeks infected mice showed a thickened smooth muscle layer compared to control and 12-weeks. Images are printed in the same final magnification (Trichrome stain, ×10). Scale bar, 100 μm.

Figure 2

Cross section showing a diffuse inflammatory infiltrate in 8-weeks infected jejunum. Note that the granulomas were scattered in both layers muscularis and mucosa. (Trichrome stain, ×40). Scale bar, 25 μm.

Figure 3

Cross section from 8-weeks infected jejunum showing the granuloma surrounded by different type of inflammatory cells including eosinophils, neutrophils and few lymphocytes (Trichrome stain, ×40). Scale bar, 25 μm.

Figure 4

Cross sections showing the myenteric plexus in control mice (A, Trichrome stain, ×40, Scale bar, 25 μm), mice after 8-weeks (B, Trichrome stain, ×100, Scale bar, 10 μm) and 12-weeks (C, Trichrome stain, ×40, Scale bar, 25 μm) of infection with Schistosoma mansoni. Note that in 8-weeks post infection the myenteric plexus contains large clusters of ganglion cells that have large nuclei with dispersed chromatin and prominent nucleoli.

Figure 5

Contractile activity in control and infected mice jejunum. Representative histograms showing the amplitude (A) and the intervals (B) of isolated jejunum from control, 8- and 12-weeks infected mice. All results are shown as mean ± SE. ^∗P < 0.05, ^∗∗P < 0.01 compared with uninfected control (n = 16).

Figure 6

Typical tracing showing the effect of L-NAME (100 μM) on PPW amplitude and intervals in (A) the uninfected control group, (B) 8-weeks post infection, (C) 12-weeks post infection. L-NAME augmented the amplitude of PPWs and decreased the intervals (n = 5).