Abstract
Epidemiological studies demonstrated that pesticide exposure, such as rotenone and paraquat, increases the risk of Parkinson’s disease (PD). Chronic systemic exposure to rotenone, a mitochondrial complex I inhibitor, could reproduce many features of PD. However, the adoption of the models is limiting because of variability in animal sensitivity and the inability of other investigators to consistently reproduce the PD neuropathology. In addition, most of rotenone models were produced in rats. Here, we tried to establish a high-reproducible rotenone model using C57BL/6J mice. The rotenone mouse model was produced by chronic systemic exposure to a low dose of rotenone (2.5 mg/kg/day) for 4 weeks by subcutaneous implantation of rotenone-filled osmotic mini pump. The rotenone-treated mice exhibited motor deficits assessed by open field, rotarod and cylinder test and gastrointestinal dysfunction. Rotenone treatment decreased the number of dopaminergic neuronal cells in the substantia nigra pars compacta (SNpc) and lesioned nerve terminal in the striatum. In addition, we observed significant reduction of cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) and the intestinal myenteric plexus. Moreover, α-synuclein was accumulated in neuronal soma in the SNpc, DMV and intestinal myenteric plexus in rotenone-treated mice. These data suggest that the low-dose rotenone mouse model could reproduce behavioral and central and peripheral neurodegenerative features of PD and be a useful model for investigation of PD pathogenesis.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disease
They reported that daily intragastric administration of rotenone (5 mg/kg) by using a stomach tube reproduced PD pathology in mice [19]
The model mice exhibited α-Syn accumulation in the enteric nervous system (ENS), the dorsal motor nucleus of the vagus (DMV), the intermediolateral nucleus of the spinal cord and the SN. These studies seem to provide an evidence that C57BL mice are available for rotenone models as well as rats used in many previous experiments [24]
Summary
Parkinson’s disease (PD) is a common neurodegenerative disease. Loss of nigrostriatal dopaminergic neurons causes motor symptoms, such as akinesia/bradykinesia, tremor, rigidity, and postural instability. Braak et al [1] reported that PD pathology, Lewy bodies and Lewy neuritis, within the central nervous system (CNS), appeared first in the brainstem (dorsal motor nucleus of the vagus (DMV)), and spread upward progressively through the substantia nigra, eventually leading to motor dysfunction, to reach the cerebral cortex. Several reports have demonstrated that PD pathology is detected within the enteric nervous system (ENS) [2,3,4]. Constipation is a well-known non-motor symptom in PD, which precedes motor symptoms by 10–20 years [5,6,7]. It has been hypothesized that PD pathology propagates from the ENS to the CNS via vagal nerve [8,9,10] the pathogenesis in sporadic PD remains unknown
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