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

Chaprov, Kirill; Teterina, E V; Roman, Andrei; Ivanova, T. A.; Goloborshcheva, Valeria V; Kucheryanu, V. G.; Morozov, Sergey G.; Lysikova, Ekaterina A.; Лыткина, О. А.; Королева, И. В.; Popova, N. Ia.; Antohin, Alexandr I; Овчинников, Р. К.; Kukharsky, Michail S.

doi:10.1134/s0026893321010039

Cited by 5 publications

(7 citation statements)

References 49 publications

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“…Briefly, all lines were previously established and maintained on a pure C57Bl6J (Charles River) genetic background in our Bioresource Collection of the IPAC RAS Centre for collective use (covered by framework FFSN-2021-0005) and provided for this experiment. Three-four-month-aged alpha synuclein knockout mice, B6(Cg)-Snca tm1.2Vlb /J [delta flox KO], maintained on the C57BL/6J genetic background, were studied as well [19].…”

Section: Animalsmentioning

confidence: 99%

“…It was developed by A.D. and supported by the Government Contract No 075-01025-23-01 with the Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences. EEG coherence was evaluated in the range of 1-30 Hz, with the averaging of data in 1-Hz bins and in "classical" EEG bands (in Hz): delta 1 (1-2), delta 2 (2-4), theta (4.0-8.0), alpha (8-12 Hz), beta 1 (12)(13)(14)(15)(16)(17)(18)(19)(20), and beta 2 (20-30.0). The values of coherence in the bands were averaged for every successive 10-min interval (for further statistical analysis) and totally for 30 min (for illustrations).…”

Section: Baseline Eeg Recording and Computation Of The Eeg Coherencementioning

confidence: 99%

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Early Effects of Alpha-Synuclein Depletion by Pan-Neuronal Inactivation of Encoding Gene on Electroencephalogram Coherence between Different Brain Regions in Mice

Vorobyov,

Deev,

Morozova

et al. 2023

Biomedicines

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Inactivation of the Snca gene in young mice by chronic injections of tamoxifen (TAM), a selective estrogen receptor modifier, has been shown to decrease the level of alpha-synuclein, a key peptide in the pathogenesis of Parkinson’s disease. In young mice, different time courses of the effect were observed in different brain areas, meaning associated disturbances in the intracerebral relations, namely in brain function after TAM-induced synucleinopathy. Methods: We analyzed electroencephalogram (EEG) coherence (“functional connectivity”) between the cortex (MC), putamen (Pt), and dopamine-producing brain regions (ventral tegmental area, VTA, and substantia nigra, SN) in two groups of two-month-old male mice. We compared EEG coherences in the conditional knockout Sncaflox/flox mice with those in their genetic background (C57Bl6J) one, two, and three months after chronic (for five days) intraperitoneal injections of TAM or the vehicle (corn oil). The EEG coherences in the TAM-treated group were compared with those in the alpha-synuclein knockout mice. Results: A significant suppression of EEG coherence in the TAM-treated mice versus the vehicle group was observed in all inter-structural relations, with the exception of MC-VTA at one and three months and VTA-SN at two months after the injections. Suppressive changes in EEG coherence were observed in the alpha-synuclein knockout mice as well; the changes were similar to those in TAM-treated mice three months after treatment. Conclusion: our data demonstrate a combined time-dependent suppressive effect induced by TAM on intracerebral EEG coherence.

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Section: Animalsmentioning

confidence: 99%

Section: Baseline Eeg Recording and Computation Of The Eeg Coherencementioning

confidence: 99%

Early Effects of Alpha-Synuclein Depletion by Pan-Neuronal Inactivation of Encoding Gene on Electroencephalogram Coherence between Different Brain Regions in Mice

Vorobyov,

Deev,

Morozova

et al. 2023

Biomedicines

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“…Moreover, several in vitro studies demonstrated that an overexpression of human alpha-synuclein was associated with enhanced cell death after MPP+ exposure [ 109 , 110 ]. MPTP administration to mice with a selective inactivation of alpha-synuclein in a few cases resulted in a dopamine deficiency and the manifestation of early clinical symptoms of a dopaminergic system dysfunction typical of the early stages of PD [ 7 ], which indirectly indicated the activation of the compensatory mechanisms of DA/MPP+ neurotransmission. It is worth emphasizing that phenotypically alpha-synuclein-knockout mice do not differ from wild-type animals [ 111 , 112 ].…”

Section: Parkinson’s Disease Is a Form Of Synucleinopathymentioning

confidence: 99%

“…In order to understand these fundamental questions, modern experimental science is developing new hybrid forms of parkinsonism in laboratory model animal systems. A toxic PD model that was initiated by single or multiple treatments of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was actively used in knockout animals lacking one or more synucleins as well as in mice overexpressing a mutant form of the human protein [ 3 , 4 , 5 , 6 , 7 ]. In this review, we focus on current findings on the potential role of the synuclein family of proteins during the MPTP-induced death of substantia nigra pars compacta (SNpc) dopaminergic neurons (DA neurons) of the midbrain.…”

Section: Introductionmentioning

confidence: 99%

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

et al. 2022

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Parkinson’s disease (PD) is one of the key neurodegenerative disorders caused by a dopamine deficiency in the striatum due to the death of dopaminergic (DA) neurons of the substantia nigra pars compacta. The initially discovered A53T mutation in the alpha-synuclein gene was linked to the formation of cytotoxic aggregates: Lewy bodies in the DA neurons of PD patients. Further research has contributed to the discovery of beta- and gamma-synucleins, which presumably compensate for the functional loss of either member of the synuclein family. Here, we review research from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity models and various synuclein-knockout animals. We conclude that the differences in the sensitivity of the synuclein-knockout animals compared with the MPTP neurotoxin are due to the ontogenetic selection of early neurons followed by a compensatory effect of beta-synuclein, which optimizes dopamine capture in the synapses. Triple-knockout synuclein studies have confirmed the higher sensitivity of DA neurons to the toxic effects of MPTP. Nonetheless, beta-synuclein could modulate the alpha-synuclein function, preventing its aggregation and loss of function. Overall, the use of knockout animals has helped to solve the riddle of synuclein functions, and these proteins could be promising molecular targets for the development of therapies that are aimed at optimizing the synaptic function of dopaminergic neurons.

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“…The speed of the test was 10 cm/s, and data were collected four times from each animal. The average speed, maximum contact area, stands, and swing speed were calculated for analysis using the CatWalk XT 10.5 software (Dalla Vecchia et al, 2018;Chaprov et al, 2021).…”

Section: Automated Gait Analysismentioning

confidence: 99%

A novel curcumin oil solution can better alleviate the motor activity defects and neuropathological damage of a Parkinson’s disease mouse model

Geng

Zhang

et al. 2022

Front. Aging Neurosci.

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Curcumin has been reported to improve or prevent movement disorders in Parkinson’s disease (PD); however, its low bioavailability is the biggest obstacle to its application. To optimize the limited efficacy of curcumin and to improve its protective effects against PD, we prepared and tested a novel curcumin oil solution. In vivo imaging was used to confirm that the curcumin oil solution has higher bioavailability than curcumin alone. To test its motor effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced movement disorders, behavioral tests, including the open-field test, pole test, rotarod test, and automated gait analysis were used. Finally, pathological evaluation using immunohistochemistry and western blotting analysis was done. Encouragingly, the behavioral test findings exhibited a better protective effect against MPTP-induced movement disorders. In addition, it had a greater protective effect on dopaminergic neurons in the compact part of the substantia nigra along with the PD process according to pathological evaluation. This novel curcumin oil solution may provide a new choice for PD prevention as a dietary supplement or clinically assisted treatment based on its better bioavailability and efficiency.

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

Cited by 5 publications

References 49 publications

Early Effects of Alpha-Synuclein Depletion by Pan-Neuronal Inactivation of Encoding Gene on Electroencephalogram Coherence between Different Brain Regions in Mice

Early Effects of Alpha-Synuclein Depletion by Pan-Neuronal Inactivation of Encoding Gene on Electroencephalogram Coherence between Different Brain Regions in Mice

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

A novel curcumin oil solution can better alleviate the motor activity defects and neuropathological damage of a Parkinson’s disease mouse model

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