Dysbiosis prevents age-dependent phenotypes in drosophila pink1B9 a fly model for parkinson's disease
Fecha
2022Autor
campusano-astorga, Jorge Mauricio
PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE
Institución
Resumen
The interaction between the enteric nervous system (ENS) and the Central nervous system (CNS), often described as the Gut-Brain Axis, consists in a bidirectional communication regulated at the endocrine, immunological and neuronal levels. The imbalance in the normal functioning of the Axis has been recently associated with several neuropsychiatric and neurodegenerative disorders. Additionally, the research about this axis could offer us new therapeutic targets for a wide range of diseases including Parkinson’s disease (PD). This is a neurodegenerative disease characterized by motor alterations, which is preceded by what is called a prodromal or premotor stage where it is possible to observe non-motor symptoms. In this thesis it is proposed to manipulate the gut microbiota at early premotor stages of a fly PD model generated by deletion in the Pink1 gene (Pink1B9), to assess whether this manipulation could affect the temporal progression of PD symptoms.
In this work, we analyzed whether there are differences in the composition of the mid-gut microbiota al 7-8 days post eclosion and we generated a Drosophila model for gut dysbiosis (microbial imbalance) by feeding flies one antibiotic (kanamycin, 0.5 mM concentration, for 14 days). By using a tracking setup we previously described we evaluated in single male flies several motor and non-motor behavioural parameters in the kanamycin-treated flies.
Results obtained in this thesis show a substantial difference in the composition of mid-gut microbiota in the Pink1B9 mutant compared with control flies. Data also show that the kanamycin treatment induces the recovery of some of the non- motor parameters studied in premotor stage PD, although there is no substantial change in the locomotor parameters at the premotor stage. On the other hand, a specific treatment only during the premotor stage has a longer effect inducing improvement in the locomotor capacity of control and mutant flies.