Neuroprotective Effects of VEGF in the Enteric Nervous System

Int J Mol Sci. 2022 Jun 17;23(12):6756. doi: 10.3390/ijms23126756.

Abstract

Although the enteric nervous system (ENS) functions largely autonomously as part of the peripheral nervous system (PNS), it is connected to the central nervous system (CNS) via the gut-brain axis. In many neurodegenerative diseases, pathological changes occur in addition to gastrointestinal symptoms, such as alpha-synuclein aggregates in Parkinson's disease, which are found early in the ENS. In both the CNS and PNS, vascular endothelial growth factor (VEGF) mediates neuroprotective and neuroregenerative effects. Since the ENS with its close connection to the microbiome and the immune system is discussed as the origin of neurodegenerative diseases, it is necessary to investigate the possibly positive effects of VEGF on enteric neurons. Using laser microdissection and subsequent quantitative RT-PCR as well as immunohistochemistry, for the first time we were able to detect and localize VEGF receptor expression in rat myenteric neurons of different ages. Furthermore, we demonstrate direct neuroprotective effects of VEGF in the ENS in cell cultures. Thus, our results suggest a promising approach regarding neuroprotection, as the use of VEGF (may) prevent neuronal damage in the ENS.

Keywords: KDR; Parkinson’s disease; VEGF; VEGFR-2; enteric nervous system; gut–brain axis; myenteric plexus; neurodegenerative diseases.

MeSH terms

  • Animals
  • Enteric Nervous System* / metabolism
  • Neurodegenerative Diseases* / metabolism
  • Neuroprotective Agents* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Parkinson Disease* / metabolism
  • Rats
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Neuroprotective Agents
  • Vascular Endothelial Growth Factor A

Grants and funding

This research received no external funding.