Abstract
There is growing awareness within the scientific community of the strong connection between the inflammation in the intestine and the pathogenesis of Parkinson’s disease (PD). In previous studies we developed a PD animal model exposing pup rats to permethrin (PERM) pesticide. Here, we intended to explore whether in our animal model there were changes in gut permeability, fecal microbiota and hepatic injury. Moreover, we tested if the co-treatment with an electrolyzed reduced (ERW) was effective to protect against alterations induced by PERM. Rats (from postnatal day 6 to 21) were gavaged daily with PERM, PERM+ERW or vehicle and gut, liver and feces were analyzed in 2-months-old rats. Increased gut permeability, measured by FITC-dextran assay, was detected in PERM group compared to control and PERM+ERW groups. In duodenum and ileum, concentration of occludin was higher in control group than those measured in PERM group, whereas only in duodenum ZO-1 was higher in control than those measured in PERM and PERM+ERW groups. Number of inflammatory focis and neutrophils as well as iNOS protein levels were higher in livers of PERM-treated rats than in those of PERM+ERW and control rats. Fecal microbiota analysis revealed that Lachnospira was less abundant and Defluviitaleaceae more abundant in the PERM group, whereas the co-treatment with ERW was protective against PERM treatment since the abundances in Lachnospira and Defluviitaleaceae were similar to those in the control group. Higher abundances of butyrate- producing bacteria such as Blautia, U.m. of Lachnospiraceae family, U.m. of Ruminococcaceae family, Papillibacter, Roseburia, Intestinimonas, Shuttleworthia together with higher butyric acid levels were detected in PERM+ERW group compared to the other groups. In conclusion, the PD animal model showed increased intestinal permeability together with hepatic inflammation correlated with altered gut microbiota. The positive effects of ERW co-treatment observed in gut, liver and brain of rats were linked to changes on gut microbiota.
Highlights
Permethrin (PERM) is a pesticide belonging to the pyrethroid family that has been used to induce Parkinson’s disease (PD) in an animal model
Post hoc comparisons revealed a significant increased intestinal permeability in PERM-treated rats compared to the control group (P0.05)
We demonstrated that perinatal oral exposure to PERM pesticide could negatively affect the fecal microbiota and could be a crucial factor contributing to the development of PD in this animal model [22]
Summary
Permethrin (PERM) is a pesticide belonging to the pyrethroid family that has been used to induce Parkinson’s disease (PD) in an animal model. It has become clear that PD is associated with a number of gastrointestinal symptoms such as constipation originating from functional and structural changes in the gut and its enteric nervous system. These disturbances happen years before the development of motor symptoms and diagnosis of PD and may provide important insights into the origin and development of the disease. Alterations of gut microbiota composition, local inflammation and increased gut permeability have been shown in PD patients Environmental factors such as exposure to pesticides seem to play a key role to initiate the pathophysiological cascade in PD. It has been postulated that the enteric nervous system (ENS) is affected early during the progression of PD even before the substantia nigra, supporting a key role for the ENS in the initiation and spreading of PD pathological process, this hypothesis remains currently controversial
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
