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Involvement of the Hippocampus and Neuronal Nitric Oxide Synapse in the Gastric Electrical Stimulation Therapy for Obesity

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Abstract

Background

Gastric electrical stimulation (GES) has been introduced for treating obesity. However, possible central mechanisms remain to be revealed. Hippocampus has been shown to be involved in the regulation of gastrointestinal functions. Changes in hypothalamic neuronal nitric oxide synthase (nNOS) have been observed in genetically obese rodents. The aim of this study was to investigate the involvement of nNOS with GES in the rodent hippocampus.

Methods

The effect of GES on gastric distension (GD) neurons was investigated using four different sets of parameters (GES-A, pulse train of standard parameters; GES-B, reduced on time; GES-C, increased pulse width, and GES-D: reduced pulse frequency), and the expression of nNOS in hippocampus was observed by fluoimmunohistochemistry staining.

Results

CA1 region neurons (90.8%) responded to GD, 50.6% of which showed excitation (GD-E neurons) and 49.4% showed inhibition (GD-I neurons). Most of GD-responsive neurons (63.3%) were excited with GES. The response to GES was associated with stimulation strength, pulse width and frequency. GD-E neurons (62.5%, 76.9%, 100%, and 62.3%) and GD-I (63.6%, 47.1%, 85.7% and 50.0%) showed excitatory responses to GES-A, GES-B, GES-C, and GES-D, respectively (P < 0.05, GES-C vs. others). nNOS immunoreactive (nNOS-IR) positive neurons were observed in hippocampus CA1, CA2-3 regions and the dentate gyrus. The expression of nNOS-IR positive neurons was significantly decreased in CA1 and CA2-3 region (P < 0.05) after GES (para-C) for 2 h.

Conclusions

Excitation of GD-responsive neurons and reduced expression of nNOS in the hippocampus are indicative of the central effect of GES.

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Acknowledgements

This study was supported by grants from the Oklahoma Center for the Advancement of Science and Technology (HR 02-034R, Dr. J.Z. Chen); The National Natural Science Foundation of China (No. 30470642 and 30670780, Dr. L. Xu) and Qingdao Science and Technique Bureau (05-1-JC-93, Dr. L. Xu).

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Authors and Affiliations

  1. Department of Pathophysiology, Medical College of Qingdao University, Qingdao, 266021, People’s Republic of China

    Luo Xu, Xiangrong Sun & Ming Tang

  2. Division of Gastroentoerlogy, University of Texas Medical Branch, 1108 the Strand, Room 221, Galveston, TX, USA

    J. D. Z. Chen

Authors
  1. Luo Xu
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  2. Xiangrong Sun
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  3. Ming Tang
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  4. J. D. Z. Chen
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Corresponding authors

Correspondence to Luo Xu or J. D. Z. Chen.

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L. Xu and X. Sun contributed equally to this work.

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Xu, L., Sun, X., Tang, M. et al. Involvement of the Hippocampus and Neuronal Nitric Oxide Synapse in the Gastric Electrical Stimulation Therapy for Obesity. OBES SURG 19, 475–483 (2009). https://doi.org/10.1007/s11695-008-9579-7

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