• Xiaoqing Mi, Mengyu Li, Yaru Zhang, Le Qu, Aoyang Xu, Junxia Xie, and Ning Song.
• School of Basic Medicine, Institute of Brain Science and Disease, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao 266071, China.
• Neuroscience. 2024 Nov 1; 559: 293301293-301.

IntroductionAlpha-synuclein (αSyn) is believed to play a central role in the pathogenesis of Parkinson's disease (PD). Cerebrospinal fluid (CSF) total αSyn were significantly lower in PD patients, whereas the aggregates were higher, and this phenomenon was further exacerbated with longer disease duration. However, whether CSF αSyn can be the cause and/or a consequence in PD is not fully elucidated.MethodWe administered 2 ng or 200 ng αSyn preformed fibrils (PFFs) by intracerebroventricular injection for consecutive 7 days in C57BL/6 mice. The olfactory function was assessed by the olfactory discrimination test and buried food-seeking test. The locomotor function was assessed by the rotarod test, pole test, open field test and CatWalk gait analysis. Phosphorylated αSyn at serine 129 was detected by the immunohistochemistry staining. Iron levels was determined by Perl's-diaminobenzidine iron staining and synchrotron-based X-ray fluorescence.ResultsThe mice did not exhibit any diffuse synucleinopathy in the brain for up to 30 weeks, although αSyn PFFs induced aggregation in SH-SY5Y cells and in the substantia nigra and striatum of mice with stereotactic injection. No impairment of motor behaviors or olfactory functions were observed, although there was a temporary motor enhancement at 1 week. We then demonstrated iron levels were comparable in certain brain regions, suggesting there was no iron deposition/redistribution occurred.ConclusionThe intraventricular injection of αSyn PFFs does not induce synucleinopathy or behavioral symptoms. These findings have implications that CSF αSyn aggregates may not necessarily contribute to the onset or progression in PD.Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.

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