Effects of gastric electrical stimulation on hippocampus gastric distension responsive neurons and the expression of motilin and neuronal nitric oxide synthase in rats

AIM: To explore the effects of gastric electrical stimulation (GES) on gastric distension (GD) responsive neurons in rat hippocampus, and study the expression of neuronal nitric oxide synthase (nNOS) and motilin (MTL) in rat brain for exploring the central mechanism of GES. METHODS: Fifty adult Wistar rats were used in this experiment. The effects of GES on GD responsive neurons in hippocampus CA1 area were observed by recording extracellular potentials of single neuron. GD responsive neurons were classified as GD-excitatory (GD-E) and GD-inhibitory (GD-I) neurons according to their responses to GD. GES with 3 sets of parameters were applied for 1 minute respectively: GES-A (6 mA, 0.3 ms, 40 Hz, 2 s-on, 3 s-off) with standard pulse trains; GES-B with increased wave width to 3 ms and GES-C with decreased frequency to 20 Hz. Two hours after GES-A was applied, we observed the expression of nNOS immunoreactive positive neurons in hippocampus by fluorescent immunohistochemistry and the content of motilin in rat brain by radioimmunoassay. RESULTS: Eighty-seven neurons in hippocampus CA1 area were recorded and 79 responded to gastric distension (GD, 3-5 mL, 10-30 s). Of the 79 GD responsive neurons, 40 (50.6%) were GD-E neurons and 39 (49.4%) were GD-I ones. 62.5%, 100% and 62.3% of GD-E neurons were excited by GES-A, -B, and -C respectively. GES-B excited more GD-E neurons than GES-C (P = 0.016). Among the GD-I neurons, 63.6%, 85.7% and 50.0% neurons were excited by GES-A, -B and -C respectively. GES-C was noted to be less effective comparing with GES-A (P = 0.041) or GES-B (P = 0.021). Two hours after GES-A was used, the expressions of nNOS positive neurons significantly decreased in the CA1 and CA2-3 area of hippocampus (16.75 ±0 .91 cells/mm² vs 20.46 ± 1.30 cells/mm², P < 0.05; 14.91 ± 1.17 cells/mm² vs 18.73 ± 1.10 cells/mm², P < 0.05) and the content of motilin peptide decreased obviously in the hypothalamus (48.93 ± 6.98 fmol/mg vs 96.23 ± 12.93 fmol/mg, P < 0.01), mesencephalon (53.17 ± 8.96 fmol/mg vs 30.96 ± 4.86 fmol/mg, P < 0.05), medulla oblongata (46.27 ± 7.83 fmol/mg vs 73.86 ± 9.37 fmol/mg, P < 0.05) and hippocampus (32.23 ± 6.51 fmol/mg vs 62.72 ± 10.07 fmol/mg, P < 0.05) by radioimmunoassay. CONCLUSION: GES may activate the gastric distension responsive neurons in hippocampus CA1 area and the excitatory effect of GES is related to the frequency and wave width of stimulation. Decreased expression of nNOS and motilin in the brain may also take part in the central mechanism of GES.