Trehalose ameliorates prodromal non-motor defi cits and aberrant protein accumulation in a rotenoneinduced mouse model of Parkinson’s disease

• Published in: Archives of pharmacal research pp. 417 - 432
• Main Authors: Soung Hee Moon, Yoonjung Kwon, Young Eun Huh, Hyun Jin Choi
• Format: Journal Article
• Language: English
• Published: 대한약학회 01.06.2022
• Subjects: 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-022-01386-2

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. KCI Citation Count: 0