2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 55(2021) N 1 p. 133-142; DOI 10.1134/S0026893321010039 Full Text

K.D. Chaprov1*, E.V. Teterina1, A.Yu. Roman1, T.A. Ivanova1, V.V. Goloborshcheva2, V.G. Kucheryanu2, S.G. Morozov2, E.A. Lysikova1, O.A. Lytkina1, I.V. Koroleva1, N.Ia. Popova3, A.I. Antohin3, R.K. Ovchinnikov1,3, M.S. Kukharsky1,3

Comparative Analysis of MPTP Neurotoxicity in Mice with a Constitutive Knockout of the α-Synuclein Gene

1Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow oblast, 142432 Russia
2Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia
3Pirogov Russian National Research Medical University, Moscow, 117997 Russia

Received - 2020-07-08; Revised - 2020-08-23; Accepted - 2020-08-30

Aggregated forms of α-synuclein are core components of pathohistological inclusions known as Lewy bodies in substantia nigra (SN) neurons of patients with Parkinson's disease (PD). The role of α-synuclein in selective loss of SN dopaminergic neurons (DNs) in PD is studied in mice knocked out in the α-synuclein gene. The new mouse strain delta flox KO with a constitutive knockout of the α-synuclein gene models the end point of in vivo deletion of the α-synuclein gene in mice with a conditional knockout and has no foreign sequence in the modified genomic locus, thus differing from all other α-synuclein knockout mouse strains. The effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is used to model PD, was compared between delta flox KO mice and mice of the well-known α-synuclein knockout strain AbKO. Subchronic MPTP administration, which models early PD, was found to reduce the dopamine content and to change the ratio of dopamine metabolites in the striatum to the same levels in delta flox KO, АbKO, and wild-type mice. Overt locomotor defects were not observed after MPTP treatment, but gait testing in a CatWalk XT (Noldus) system revealed identical gait deviations in mice of the two strains and control wild-type mice. Based on the findings, a similar mechanism of neurotoxic damage to DNs was assumed for delta flox KO and AbKO mice.

Parkinson's disease, α-synuclein, genetic knockout, dopamine, MPTP