Nigrostriatal 6-hydroxydopamine lesions increase alpha-synuclein levels and permeability in rat colon

• DOI: 10.1016/j.neurobiolaging.2023.05.007
• Publication Date: 2023-05-07T09:45:30Z
• Authors: Hengjing Cui; Joshua D. Elford; Okko Alitalo; Paula Perez-Pardo; Janne Tampio; Kristiina M. Hutt...; Aletta Kraneveld; Markus M. Forsberg; Timo T. Myöhänen; Aaro J. Jalkanen
• Keywords: Nigrostriatal pathway; Medial forebrain bundle; Oxidopamine

Increasing evidence suggests that the gut–brain axis plays a crucial role in Parkinson's disease (PD). The abnormal accumulation of aggregated alpha-synuclein (aSyn) brain is key pathological feature PD. Intracerebral 6-hydroxydopamine (6-OHDA) widely used dopaminergic lesion model It exerts no aSyn pathology brain, but changes gut have not been assessed. Here, 6-OHDA was administered unilaterally either to rat medial forebrain bundle (MFB) or striatum. Increased levels glial fibrillary acidic protein ileum and colon were detected at 5 weeks postlesion. decreased Zonula occludens 1 barrier integrity score, suggesting increased colonic permeability. total Ser129 phosphorylated elevated after MFB lesion. Both lesions generally aSyn, pS129 ionized calcium-binding adapter molecule (Iba1) lesioned In conclusion, 6-OHDA-induced nigrostriatal damage leads cell activation particularly colon, interactions PD are bidirectional detrimental process may start brain.