From psychology to physicality: how nerve growth factor transduces early life stress into gastrointestinal motility disorders later in life

Chi Fung Willis Chow, Sijia Che, Hong Yan Qin, Hiu Yee KWAN, Zhaoxiang BIAN*, Hoi Leong Xavier WONG

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Environmental stressors in early childhood can have a detrimental impact later in life, manifesting in functional gastrointestinal disorders including irritable bowel syndrome (IBS). The phenomenon is also observed in rodents, where neonatal–maternal separation, a model of early life stress, induces phenotypes similar to IBS; however, the underlying mechanisms remain unelucidated. Our recent study provided a mechanism for the pathogenesis in the gut, demonstrating that increased visceral hyperalgesia resulted from the expansion of the intestinal stem cell compartment leading to increased differentiation and proliferation of serotonin (5-hydroxytryptamine/5-HT)-producing enterochromaffin cells. Moreover, it identified nerve growth factor (NGF) as a key mediator of the pathogenesis; surprisingly, it exerts its effect via cross talk with Wnt/β-catenin signaling. This article addresses the roles of NGF in driving IBS and its potential clinical implications, outstanding questions in how psychological stimuli are transduced into physical phenotypes, as well as future directions of our findings. Abbreviations: 5-HT: 5-hydroxytryptamine/serotonin; BDNF: brain-derived neurotrophic factor; CRF: corticotrophin-releasing factor; EC: enterochromaffin; ENS: enteric nervous system; GI: gastrointestinal; GPCR: G-protein-coupled receptor; IBS (-D): irritable bowel syndrome (diarrhea predominant); LRP5/6: low-density lipoprotein receptor-related protein 5/6; MAPK: mitogen-activated protein kinase; NGF: nerve growth factor; NMS: neonatal–maternal separation; PI3K: phosphoinositode3-kinase; PLCγ: phospholipase c, gamma subtype; TrkA: tropomyosin receptor kinase A.

Original languageEnglish
Pages (from-to)1824-1829
Number of pages6
JournalCell Cycle
Volume18
Issue number16
DOIs
Publication statusPublished - 18 Aug 2019

Scopus Subject Areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

User-Defined Keywords

  • intestinal stem cells
  • Irritable bowel syndrome
  • NGF
  • serotonin
  • TrkA
  • Wnt signaling

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