Date: Sunday, October 7, 2018
Session Title: Parkinsonism, MSA, PSP (Secondary and Parkinsonism-Plus)
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: The aim of this study was to examine the effect of mannitol treatment in a mice model of MSA.
Background: Alpha-synuclein aggregation represents the pathological hallmark of α-synucleinopathies like Parkinson`s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). MSA is a fatal neurodegenerative disease characterized by pathological accumulation of alpha-synuclein aggregates in oligodendrocytes. No effective treatments are currently available for MSA patients. Recently, the ability of mannitol to interfere with the aggregation process of α-synuclein was shown in vitro and in mice and drosophila models of Parkinson’s disease.
Methods: We hypothesized that mannitol treatment will lead to decreased α-synuclein pathology in the brain of transgenic mice overexpressing α-synuclein in oligodendrocytes under the proteolipid protein promoter (PLP-α-synuclein mouse model of MSA). Six months old wild type and PLP-α-synuclein mice were allocated to four groups and received 5 weekly intraperitoneal injections of mannitol or vehicle. In some of the experiments PLP-α-synuclein mice were also treated with the mitochondrial toxin 3-nitropropionic acid (3-NP) to model full-blown MSA. During a 12-week treatment period, motor behavior was assessed. Brains samples were collected for neuropathological analysis.
Results: Chronic systemic mannitol treatment of PLP-α-synuclein mice led to partial motor improvement. Pathological analysis demontrated rescue of nigral dopaminergic and striatal neurons and decreased astroglial and inflammatory responses.
Conclusions: Our findings demonstrate beneficial effects of chronic mannitol treatment in transgenic PLP-α-synuclein mice. However, the translatability of these results into human patients is yet to be determined.
To cite this abstract in AMA style:N. Lev, Y. Barhum. Effects of mannitol treatment in a mice model of multiple system atrophy (MSA) [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/effects-of-mannitol-treatment-in-a-mice-model-of-multiple-system-atrophy-msa/. Accessed December 5, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-mannitol-treatment-in-a-mice-model-of-multiple-system-atrophy-msa/