Kanamycin treatment in the pre-symptomatic stage of a Drosophila PD model prevents the onset of non-motor alterations

Neuropharmacology. 2023 Sep 15:236:109573. doi: 10.1016/j.neuropharm.2023.109573. Epub 2023 May 15.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor alterations, which is preceded by a prodromal stage where non-motor symptoms are observed. Over recent years, it has become evident that this disorder involves other organs that communicate with the brain like the gut. Importantly, the microbial community that lives in the gut plays a key role in this communication, the so-called microbiota-gut-brain axis. Alterations in this axis have been associated to several disorders including PD. Here we proposed that the gut microbiota is different in the presymptomatic stage of a Drosophila model for PD, the Pink1B9 mutant fly, as compared to that observed in control animals. Our results show this is the case: there is basal dysbiosis in mutant animals evidenced by substantial difference in the composition of midgut microbiota in 8-9 days old Pink1B9 mutant flies as compared with control animals. Further, we fed young adult control and mutant flies kanamycin and analyzed motor and non-motor behavioral parameters in these animals. Data show that kanamycin treatment induces the recovery of some of the non-motor parameters altered in the pre-motor stage of the PD fly model, while there is no substantial change in locomotor parameters recorded at this stage. On the other hand, our results show that feeding young animals the antibiotic, results in a long-lasting improvement of locomotion in control flies. Our data support that manipulations of gut microbiota in young animals could have beneficial effects on PD progression and age-dependent motor impairments. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".

Keywords: Aging; Drosophila; Microbiota; Parkinson's disease; Pink1; Presymptomatic stage.

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Drosophila
  • Kanamycin
  • Parkinson Disease*
  • Protein Kinases

Substances

  • Kanamycin
  • Anti-Bacterial Agents
  • Protein Kinases