Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain

Authors

  • Yunqiao Xiao Institute of Neuroscience, Chongqing Medical University, Chongqing, China; University-town hospital of Chongqing Medical University, Chongqing, China
  • Gengyi Wang Institute of Neuroscience, Chongqing Medical University, Chongqing, China
  • Guiqiong He Institute of Neuroscience, Chongqing Medical University, Chongqing, China
  • Wanxiang Qin Department of Pain Care, Southwest Hospital, Army Medical University, Chongqing, China
  • Ying Shi Department of Pain Care, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

DOI:

https://doi.org/10.17305/bb.2024.10441

Keywords:

Neuropathic pain, astrocytes, Rab8a, vesicular transport, SNARE proteins

Abstract

Neuropathic pain (NPP) remains a clinically challenging condition, driven by the activation of spinal astrocytes and the complex release of inflammatory mediators. This study aimed to examine the roles of Rab8a and SNARE complex proteins in activated astrocytes to uncover the underlying mechanisms of NPP. The research was conducted using a rat model with chronic constriction injury (CCI) of the sciatic nerve and primary astrocytes treated with lipopolysaccharide. Enhanced expression of Rab8a was noted specifically in spinal dorsal horn astrocytes through immunofluorescence. Electron microscopy observations showed increased vesicular transport and exocytic activity in activated astrocytes, which was corroborated by elevated levels of inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α detected through quantitative PCR. Western blot analyses confirmed significant upregulation of Rab8a, VAMP2, and Syntaxin16 in these cells. Furthermore, the application of botulinum neurotoxin type A (BONT/A) reduced the levels of vesicle transport-associated proteins, inhibiting vesicular transport in activated astrocytes. These findings suggest that the Rab8a/SNARE pathway in astrocytes enhances vesicle transport and anchoring, increasing the secretion of bioactive molecules that may play a crucial role in the pathophysiology of NPP. Inhibiting this pathway with BONT/A offers a novel therapeutic target for managing NPP, highlighting its potential utility in clinical interventions.

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Published

30-04-2024

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Section

Molecular Biology

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How to Cite

1.
Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain. Biomol Biomed [Internet]. 2024 Apr. 30 [cited 2024 May 27];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/10441