Trehalose ameliorates prodromal non-motor defi cits and aberrant protein accumulation in a rotenoneinduced mouse model of Parkinson’s disease
- Resource Type
- Article
- Authors
- Soung Hee Moon; Yoonjung Kwon; Young Eun Huh; Hyun Jin Choi
- Source
- Archives of Pharmacal Research, 45(6), pp.417-432 Jun, 2022
- Subject
- 약학
- Language
- English
- ISSN
- 1976-3786
0253-6269
Trehalose has been recently revealed as anattractive candidate to prevent and modify Parkinson’s disease(PD) progression by regulating autophagy; however,studies have only focused on the reduction of motor symptomsrather than the modulation of disease course from prodromalstage. This study aimed to evaluate whether trehalosehas a disease-modifying eff ect at the prodromal stage beforethe onset of a motor defi cit in 8-week-old male C57BL/6mice exposed to rotenone. We found signifi cant decreasein tyrosine hydroxylase immunoreactivity in the substantianigra and motor dysfunction after 2 weeks rotenonetreatment. Mice exposed to rotenone for a week showed anaccumulation of protein aggregates in the brain and prodromalnon-motor defi cits, such as depression and olfactorydysfunction, prior to motor defi cits. Trehalose signifi cantlyimproved olfactory dysfunction and depressive-like behaviorsand markedly reduced α-synuclein and p62 deposition in the brain. Trehalose further ameliorated motor impairmentand loss of nigral tyrosine hydroxylase-positive cellsin rotenone-treated mice. We demonstrated that prodromalnon-motor signs in a rotenone-induced PD mouse modelare associated with protein aggregate accumulation in thebrain and that an autophagy inducer could be valuable toprevent PD progression from prodromal stage by regulatingabnormal protein accumulation.