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Brain-Derived Neurotrophic Factor Contributes to Colonic Hypermotility in a Chronic Stress Rat Model

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Abstract

Background

Brain-derived neurotrophic factor (BDNF) has prokinetic effects on gut motility and is increased in the colonic mucosa of irritable bowel syndrome.

Aims

We aimed to investigate the possible involvement of BDNF in stress-induced colonic hypermotility.

Methods

Male Wistar rats were exposed to daily 1-h water avoidance stress (WAS) or sham WAS for 10 consecutive days. The presence of BDNF and substance P (SP) in the colonic mucosa was determined using enzyme immunoassay kits. Immunohistochemistry and western blotting were performed to assess the expression of BDNF and its receptor, TrkB. The contractions of muscle strips were studied in an organ bath system.

Results

Repeated WAS increased the fecal pellet expulsion and spontaneous contractile activities of the colonic muscle strips. Both BDNF and SP in the colonic mucosa were elevated following WAS. Immunohistochemistry revealed the presence of BDNF and TrkB in the mucosa and myenteric plexus. BDNF and TrkB were both up-regulated in colon devoid of mucosa and submucosa from the stressed rats compared with the control. BDNF pretreatment caused an enhancement of the SP-induced contraction of the circular muscle (CM) strips. TrkB antibody significantly inhibited the contraction of the colonic muscle strips and attenuated the excitatory effects of SP on contractions of the CM strips. Repeated WAS increased the contractile activities of the CM strips induced by SP after BDNF pretreatment, and this effect was reversed by TrkB antibody.

Conclusions

The colonic hypermotility induced by repeated WAS may be associated with the increased expression of endogenous BDNF and TrkB. BDNF may have potential clinical therapeutic use in modulating gut motility.

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Authors and Affiliations

  1. Department of Gastroenterology, Renmin Hospital of Wuhan University, Number 238, Jiefang Road, Wuhan, 430060, Hubei Province, China

    Xiaojing Quan, Hesheng Luo, Han Fan, Qincai Tang, Wei Chen, Ning Cui, Guang Yu & Hong Xia

  2. Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, China

    Hong Xia

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  1. Xiaojing Quan
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  2. Hesheng Luo
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  3. Han Fan
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  4. Qincai Tang
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  5. Wei Chen
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  7. Guang Yu
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  8. Hong Xia
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Correspondence to Hesheng Luo.

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Quan, X., Luo, H., Fan, H. et al. Brain-Derived Neurotrophic Factor Contributes to Colonic Hypermotility in a Chronic Stress Rat Model. Dig Dis Sci 60, 2316–2326 (2015). https://doi.org/10.1007/s10620-015-3695-8

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  • DOI: https://doi.org/10.1007/s10620-015-3695-8

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