Paraquat-induced model of parkinson’s disease and detection of phosphorylated α-synuclein in the enteric nervous system of rats

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder with a variety of motor and non-motor features. Non-motor symptoms, such as gastrointestinal dysfunction, usually set in 5 to 15 years earlier than motor manifestations. Cytoplasmic aggregates of phosphorylated α-synuclein are a typical marker of PD. They are observed not only in cerebral neurons but also in intramural plexuses of the intestine. Therefore, it is essential to investigate the peripheral component of the molecular pathogenesis of the disease using PD models, including those involving the use of parkinsonian neurotoxins, such as the well-known herbicide paraquat. The aim of this study was to identify a complex of early α-synuclein-related changes induced by long-term systemic administration of paraquat to rats at doses of 6 mg/kg. The open-field test revealed a decline in the motor activity of the experimental animals; the tapered beam walking test demonstrated a two-fold increase (р = 0.044) in the number of left paw slips. Besides, the intensity of staining for tyrosine hydroxylase (TH) in the substantia nigra and myenteric plexus fibers was 50% (р = 0.033) and 20% (р = 0.01) lower, respectively, in the main group than in the controls. Phosphorylated α-synuclein content was increased in the cell bodies of myenteric neurons and in TH-positive nervous fibers of the experimental animals. Changes indicating the development of peripheral α-synuclein pathology in the early stage of induced PD are similar to the changes observed in patients with PD at the onset of the disease. The proposed paraquat regimen could be very promising for PD modeling.

Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease

“…The distribution of α-synuclein in the tissue might depend on the connexin 32 (Cx32)-based activity of gap junctions between cells and within the astroglial syncytium [32]. As we and others have shown before, this is confirmed by extra-brain localization of α-synuclein in PD patients, thereby suggesting the retrograde dissemination of α-synuclein forms olfactory bulbs and intestinal autonomic neurons on the brainstem structures and determining the staging of synucleinopathy development [30,[33][34][35].…”