Idebenone improves motor dysfunction, learning and memory by regulating mitophagy in MPTP-treated mice.

Abstract

The progression of Parkinson's disease (PD) is often accompanied by the loss of substantia nigra dopaminergic neurons, mitophagy damage, learning, and memory impairment. Idebenone is a therapeutic drug that targets the mitochondria of neurodegenerative diseases, but its role in Parkinson's disease and its pathological mechanism are still unclear. The purpose of this study was to investigate whether idebenone could improve behavioral disorders, especially motor, learning, and memory disorders, in mouse PD models and to explore its molecular mechanism. In the present study, C57BL-6 mice underwent intraperitoneal injection of MPTP (30 mg/kg) once a day for five consecutive days. Then, a 200 mg/kg dose was given as a single daily gavage of idebenone dissolved in water for 21 days after the successful establishment of the subacute MPTP model. Motor, learning, and memory were measured by a water maze and a rotarod test. Our results showed that idebenone could reduce MPTP-induced dopaminergic neuron damage and improve movement disorders, memory, and learning ability, which may be associated with upregulating mitochondrial autophagy-related outer membrane proteins VDAC1 and BNIP3 and activating the Parkin/PINK1 mitochondrial autophagy pathway. To confirm whether idebenone promotes the smooth progression of autophagy, we used eGFP-mCherry-LC3 mice to construct a subacute model of Parkinson's disease and found that idebenone can increase autophagy in dopaminergic neurons in Parkinson's disease. In summary, our results confirm that idebenone can regulate the expression of the mitochondrial outer membrane proteins VDAC1 and BNIP3, activate Parkin/PINK1 mitophagy, promote the degradation of damaged mitochondria, reduce dopaminergic neuron damage, and improve behavioral disorders in Parkinson's disease mice.

• Authors: Junqiang Yan, Wenjie Sun, Mengmeng Shen, Yongjiang Zhang, Menghan Jiang, Anran Liu, Hongxia Ma, Xiaoyi Lai, Jiannan Wu
• Journal: Cell death discovery (Cell Death Discov) Vol. 8 Issue 1 Pg. 28 (Jan 17 2022) ISSN: 2058-7716 [Print] United States
• PMID: 35039479 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).