Neuronal tissue collection from intra-cranial instruments used in deep brain stimulation surgery for Parkinson's disease with implications for study of alpha-synuclein.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      alpha-Synuclein*/metabolism ; Deep Brain Stimulation*/methods ; Neurons*/metabolism ; Neurons*/pathology ; Parkinson Disease*/metabolism ; Parkinson Disease*/therapy ; Parkinson Disease*/pathology ; Parkinson Disease*/surgery; Humans ; Brain/metabolism ; Brain/pathology ; Brain/surgery ; Essential Tremor/therapy ; Essential Tremor/metabolism
    • Abstract:
      Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson's disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is collected from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg of protein (n = 15), on average, was collected from surgical instruments. Light microscopy revealed axons, capillaries, and blood cells as the primary components of purified tissue (n = 3). ELISA assay further confirmed the presence of neuronal and glial tissue in DBS samples (n = 4). Further analysis was conducted using western blot, demonstrating that multiple αSyn antibodies are reactive in PD (n = 5) and ET (n = 3) samples; truncated αSyn (1-125 αSyn) was significantly increased in PD (n = 5) compared to ET (n = 3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that multiple forms of αSyn can be detected from living PD patients with this method.
      (© 2024. The Author(s).)
    • Comments:
      Update of: Res Sq. 2024 May 20:rs.3.rs-4369598. doi: 10.21203/rs.3.rs-4369598/v1. (PMID: 38826474)
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    • Grant Information:
      R01 NS100876 United States NS NINDS NIH HHS; RF1 NS129567 United States NS NINDS NIH HHS; RF1NS129567, R01NS100876 United States NH NIH HHS
    • Contributed Indexing:
      Keywords: Alpha-synuclein; Deep brain stimulation; Essential tremor; Neurodegeneration; Parkinson’s disease
    • Accession Number:
      0 (alpha-Synuclein)
    • Publication Date:
      Date Created: 20240916 Date Completed: 20240916 Latest Revision: 20240924
    • Publication Date:
      20240925
    • Accession Number:
      PMC11405830
    • Accession Number:
      10.1038/s41598-024-72542-5
    • Accession Number:
      39284884