Abstract
Trehalose has been recently revealed as an attractive candidate to prevent and modify Parkinson’s disease (PD) progression by regulating autophagy; however, studies have only focused on the reduction of motor symptoms rather than the modulation of disease course from prodromal stage. This study aimed to evaluate whether trehalose has a disease-modifying effect at the prodromal stage before the onset of a motor deficit in 8-week-old male C57BL/6 mice exposed to rotenone. We found significant decrease in tyrosine hydroxylase immunoreactivity in the substantia nigra and motor dysfunction after 2 weeks rotenone treatment. Mice exposed to rotenone for a week showed an accumulation of protein aggregates in the brain and prodromal non-motor deficits, such as depression and olfactory dysfunction, prior to motor deficits. Trehalose significantly improved olfactory dysfunction and depressive-like behaviors and markedly reduced α-synuclein and p62 deposition in the brain. Trehalose further ameliorated motor impairment and loss of nigral tyrosine hydroxylase-positive cells in rotenone-treated mice. We demonstrated that prodromal non-motor signs in a rotenone-induced PD mouse model are associated with protein aggregate accumulation in the brain and that an autophagy inducer could be valuable to prevent PD progression from prodromal stage by regulating abnormal protein accumulation.
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This research was supported by the Bio & Medical Technology Development Program (Grant number NRF-2016M3A9E8941671) and the Mid-Career Researcher Program (Grant number NRF-2021R1A2C1013180) of the National Research Foundation funded by the Korean government, MSIP.
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Supplementary material 1 (JPG 730.8 kb)—Effect of trehalose on motor impairment induced by rotenone in the Parkinson’s disease (PD) mouse model. a Time on the rod during the rotarod test in mice treated with 1 mg/kg rotenone (ROT_1), 1 mg/kg rotenone plus 2 g/kg trehalose (ROT + TRE), or the vehicle (CON) for 2 weeks (n = 9–10/group; one-way ANOVA). b Immunohistochemistry analysis (left) and quantification (right) of immunoreactivity against tyrosine hydroxylase (TH) in the SN of mouse brain (n = 6; one-way ANOVA). Scale bars = 100 μm. *p < 0.05
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Supplementary material 2 (JPG 1996.6 kb)—Effect of trehalose on pathology of representative marker in the Parkinson’s disease (PD) mouse model. a Immunohistochemistry analysis of phophorylated-α-synuclein (phospho-α-syn) levels in the olfactory bulb (OB), striatum, substantia nigra (SN) and dentate gyrus (DG) of hippocampus in mice. Scale bars = 100 μm
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Moon, S., Kwon, Y., Huh, Y. et al. Trehalose ameliorates prodromal non-motor deficits and aberrant protein accumulation in a rotenone-induced mouse model of Parkinson’s disease. Arch. Pharm. Res. 45, 417–432 (2022). https://doi.org/10.1007/s12272-022-01386-2
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DOI: https://doi.org/10.1007/s12272-022-01386-2