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RAS BiologyБиохимия Biochemistry

  • ISSN (Print) 0320-9725
  • ISSN (Online) 3034-5294

THE DOUBLE TOXIC MPTP + CBE PRESYMPTOMATIC PARKINSON-LIKE PHENOTYPE IN MICE

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PII
S30345294S0320972525080065-1
DOI
10.7868/S3034529425080065
Publication type
Article
Status
Published
Authors
S.N. Pchelina
  • Affiliation:
    Petersburg Nuclear Physics Institute, Kurchatov Institute National Research Center
    Pavlov First Saint Petersburg State Medical University
A.I. Bezrukova
  • Affiliation:
    Petersburg Nuclear Physics Institute, Kurchatov Institute National Research Center
    Pavlov First Saint Petersburg State Medical University
M.M. Rudenok
  • Affiliation: Institute of Molecular Genetics, Kurchatov Institute National Research Centre
A.S. Zhuravlev
  • Affiliation:
    Petersburg Nuclear Physics Institute, Kurchatov Institute National Research Center
    Pavlov First Saint Petersburg State Medical University
I.N. Rybolovlev
  • Affiliation: Institute of Molecular Genetics, Kurchatov Institute National Research Centre
A.O. Lavrinova
  • Affiliation:
    Petersburg Nuclear Physics Institute, Kurchatov Institute National Research Center
    Pavlov First Saint Petersburg State Medical University
G.V. Baydakova
  • Affiliation: Research Center of Medical Genetics
M.A. Nikolaev
  • Affiliation:
    Petersburg Nuclear Physics Institute, Kurchatov Institute National Research Center
    Pavlov First Saint Petersburg State Medical University
M.S. Nesterov
  • Affiliation: Scientific Center of Biomedical Technologies, Federal Medical and Biological Agency of Russia
D.A. Abaimov
  • Affiliation: Research Centre of Neurology
V.N. Pidurchina
  • Affiliation: Petersburg Nuclear Physics Institute, Kurchatov Institute National Research Center
S.A. Partevyan
  • Affiliation: Institute of Molecular Genetics, Kurchatov Institute National Research Centre
E.I. Semenova
  • Affiliation: Institute of Molecular Genetics, Kurchatov Institute National Research Centre
T.S. Usenko
  • Affiliation:
    Petersburg Nuclear Physics Institute, Kurchatov Institute National Research Center
    Pavlov First Saint Petersburg State Medical University
E.Y. Zakharova
  • Affiliation: Institute of Molecular Genetics, Kurchatov Institute National Research Centre
A.K. Emelyanov
  • Affiliation:
    Petersburg Nuclear Physics Institute, Kurchatov Institute National Research Center
    Pavlov First Saint Petersburg State Medical University
M.I. Shadrina
  • Affiliation: Institute of Molecular Genetics, Kurchatov Institute National Research Centre
P.A. Slominsky
  • Affiliation: Institute of Molecular Genetics, Kurchatov Institute National Research Centre
Volume/ Edition
Volume 90 / Issue number 8
Pages
1148-1162
Abstract
The deficiency of glucocerebrosidase (GCase) encoded by the gene, leads to the autosomal recessive Gaucher disease and highly increased risk of developing Parkinson's disease (PD). In order to study the effect of GCase dysfunction on neurodegeneration, we evaluated the GCase activity, lysosphingolipid content, extent of dopaminergic neuron degeneration in the substantia nigra (SN), and levels of dopamine (DA) and total and oligomeric α-synuclein (α-Syn) in the brain of mice with the presymptomatic stage of parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in combination with a single injection of the GCase selective inhibitor conduritol-β-epoxide (CBE) (100 mg/kg body weight). A single injection of CBE led to a ~50% decrease in the GCase activity, significant increase in the lysosphingolipid content, and striatal accumulation of oligomeric α-Syn in the mouse brain. Assessment of the DA neuron degeneration in the SN 14 days after injection by immunohistochemical staining for tyrosine hydroxylase (TH) demonstrated a twice more pronounced reduction in the number of TH+ neurons in MPTP + CBE mice compared to MPTP only-treated animals (14% vs. 29%, respectively; < 0.0001). The double neurotoxic (MPTP+CBE) model was also characterized by a decrease in the DA content and more pronounced accumulation of total α-Syn in the striatum. Overall, we demonstrated that inhibition of the GCase activity leads to the α-Syn accumulation and further exacerbation of the MPTP-induced pathology. The described double toxic MPTP + CBE mouse model can be used for the screening of neuroprotective drugs in approaches aimed at increasing the GCase activity.
Keywords
болезнь Паркинсона глюкоцереброзидаза КБЭ МФТП мышиная модель
Date of publication
15.07.2025
Year of publication
2025
Number of purchasers
0
Views
85

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