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Fibroblast growth factor-2 prevents synaptic pathology in minimal hepatic encephalopathy via NRG1/ErbB4 signaling
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  • Qichuan Zhuge,
  • Weishan Zhuge,
  • Jian Wang,
  • Yiru Ye,
  • Xiaoai Lu,
  • Ruiming You,
  • Leping Liu,
  • He Yu,
  • Xuebao Wang,
  • saidan ding
Qichuan Zhuge
Wenzhou Medical University First Affiliated Hospital
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Weishan Zhuge
Wenzhou Medical College First Affiliated Hospital
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Jian Wang
Wenzhou Medical University First Affiliated Hospital
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Yiru Ye
Wenzhou Medical University First Affiliated Hospital
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Xiaoai Lu
Wenzhou Medical University First Affiliated Hospital
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Ruiming You
Wenzhou Medical University First Affiliated Hospital
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Leping Liu
Wenzhou Medical University First Affiliated Hospital
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He Yu
Wenzhou Medical University First Affiliated Hospital
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Xuebao Wang
Wenzhou Medical University
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saidan ding
Wenzhou Medical University First Affiliated Hospital
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Abstract

Background and Purpose: Minimal hepatic encephalopathy (MHE) is implicated in the impairment of memory function. Fibroblast growth factor-2 (FGF2) is involved in modulating synaptic and neuronal formation. Experimental Approach: The aim of this study is to examined the impacts of FGF2 on MHE pathology. Our study addressed whether FGF2 could trigger neuregulin 1 (NRG1) release to ameliorate synaptic impairment in MHE rats and in primary cultured neurons. Key Results: The results showed the decreased FGF2 expression in MHE brains. After treatment with FGF2, secreted neuregulin 1 (NRG1) and ErbB4 were increased, and the interaction of the 2 proteins was enhanced. Additionally, treatment with FGF2 or NRG1 induced synaptic formation, with increase in the activity of synapse and the density of dendritic spine, through Sirt1. NRG1 signaling was prevented by administration of FGF2, which acts through the FGFR1 in MHE rats. Finally, intracerebroventricular injection with FGF2 or NRG1 mitigated the impairment of synaptogenesis. Conclusions and Implications: The data suggest that FGF2 may be a promising latent therapeutic reagent for MHE pathogenesis.

Peer review status:POSTED

11 Jan 2020Submitted to British Journal of Pharmacology
17 Feb 2020Assigned to Editor
17 Feb 2020Submission Checks Completed