Neuroprotective effects of an engineered commensal bacterium in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Parkinson disease mouse model via producing glucagon-like peptide-1

J Neurochem. 2019 Aug;150(4):441-452. doi: 10.1111/jnc.14694. Epub 2019 Apr 1.

Abstract

While glucagon-like peptide-1 (GLP-1) was reported to have a positive impact on Parkinson disease, it is extremely short half-life greatly hindered its clinical use. In this study, the mouse strain MG1363-pMG36e-GLP-1 was engineered to continuously express GLP-1 to treat Parkinson disease in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated Parkinson disease model. In our study, oral supplementation with MG1363-pMG36e-GLP-1 significantly (p < 0.05) reduced MPTP-induced locomotor impairments, increased tyrosine hydroxylase-positive neurons, suppressed microglia and astrocyte activation, and down-regulated expression of several inflammation-related molecules. In addition, MG1363-pMG36e-GLP-1 significantly (p < 0.01) reduced intestinal pathogen Enterobacteriaceae and markedly enhanced the number of probiotic Lactobacillus and Akkermansia. These data suggest that MG1363-pMG36e-GLP-1 could be a novel therapeutic means for Parkinson disease.

Keywords: GLP-1; MG1363-pMG36e-GLP-1; Parkinson disease; TLR-4; high-throughput sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gastrointestinal Microbiome*
  • Glucagon-Like Peptide 1 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / pathology

Substances

  • Glucagon-Like Peptide 1

Associated data

  • GENBANK/SRP156609