2. Academic Validation
  3. Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress

Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress

  • CNS Neurosci Ther. 2024 Feb;30(2):e14611. doi: 10.1111/cns.14611.
Guang-Bing Duan 1,  Jun-Wen Wang 1,  Hui-Hui Sun 1,  Zhi-Yu Dong 1,  Yan Zhang 1,  Zhen-Xiang Wang 1,  Ye Chen 1,  Ying Chen 1,  Ying Huang 2,  Shu-Chang Xu 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 2 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Ministry of Education), Department of Physiology and Pharmacology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
PMID: 38353051 DOI: 10.1111/cns.14611
Abstract

Aims: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process.

Methods: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety- and depression-like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot.

Results: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety-like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety-like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N-methyl-D-aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety-like behaviors.

Conclusions: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS-like symptoms. These findings may give insight into the treatment of IBS and related psychological distress.

Keywords

EphB2; NMDA receptors; basolateral amygdala; irritable bowel syndrome; psychological stress; visceral hypersensitivity.

Figures
Products