Modeling of preclinical and early clinical stages of Parkinson's disease

Khaindrava V.G.; Kozina E.A.; Kucherianu V.G.; Kryzhanovskiĭ G.N.; Kudrin V.S.; Klodt P.D.; Bocharov E.V.; Raevskiĭ K.S.; Ugriumov M.V.

doi:https://doi.org/

Khaindrava V.G.

Institut normal'noĭ fiziologii im. P.K. Anokhina RAMN

Kozina E.A.

Institut biologii razvitiia im. N.K. Kol'tsova RAN

Kucherianu V.G.

Institut obshcheĭ patologii i patofiziologii RAMN

Kryzhanovskiĭ G.N.

Kudrin V.S.

Institut farmakologii im. V.V. Zakusova RAMN, Moskva

Klodt P.D.

Institut farmakologii im. V.V. Zakusova RAMN, Moskva

Bocharov E.V.

Institut farmakologii im. V.V. Zakusova RAMN, Moskva

Raevskiĭ K.S.

Institut normal'noĭ fiziologii im. P.K. Anokhina RAMN;
Institut farmakologii im. V.V. Zakusova RAMN, Moskva

Ugriumov M.V.

Institut biologii razvitiia im. N.K. Kol'tsova RAN, Moskva

Modeling of preclinical and early clinical stages of Parkinson's disease

Authors:

Khaindrava V.G., Kozina E.A., Kucherianu V.G., Kryzhanovskiĭ G.N., Kudrin V.S., Klodt P.D., Bocharov E.V., Raevskiĭ K.S., Ugriumov M.V.

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Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2010;110(7): 41‑47

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To cite this article:

Khaindrava VG, Kozina EA, Kucherianu VG, et al. . Modeling of preclinical and early clinical stages of Parkinson's disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2010;110(7):41‑47. (In Russ.)

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

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Abstract:

The first symptoms of Parkinson's disease manifest 20-30 years after the disease onset when the most dopaminergic neurons degenerated. Therefore, it is necessary to work out preclinical diagnostics and preventive treatment of this disease. Modeling of preclinical and early stages of Parkinson's disease was conducted in mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP). The changes in motor behavior were not observed in mice by 14 day after MPTP injections in dose 12 mg/ kg two times with interval of two hours. In the striatum, the region of dopaminergic axon projection, the content of dopamine and number of dopaminergic axons decreased by 57% and 59%, respectively, i.e. there were no changes in dopamine in single axons. In the substantia nigra, the region of dopamine neuron localization, the content of dopamine did not change though the total number of neurons decreased by 28%. However the dopamine content in remained neurons was higher by 77% compared to the control that indirectly indicated the compensatory enhancement of dopamine synthesis. After the MPTP injections in dose 4×12 mg/kg, there were changes in motor behavior of mice in the most sensitive tests. In the striatum, the dopamine content and number of dopaminergic axons decreased by 75% and 68%, respectively. In the substantia nigra, there were no changes in dopamine content but the number of dopaminergic neurons decreased by 43%. The intraneuronal dopamine content increased by more than 70%. In conclusion, we constructed the models of preclinical stage (two-time MPTP injections) and transition phase from presymptomatic to symptomatic stage (four times of MPTP injections) of Parkinson's disease.

Keywords:

dopamine

substantia nigra

striatum

neurotoxin

Authors:

Khaindrava V.G.

Institut normal'noĭ fiziologii im. P.K. Anokhina RAMN

Kozina E.A.

Institut biologii razvitiia im. N.K. Kol'tsova RAN

Kucherianu V.G.

Institut obshcheĭ patologii i patofiziologii RAMN

Kryzhanovskiĭ G.N.

Kudrin V.S.

Institut farmakologii im. V.V. Zakusova RAMN, Moskva

Klodt P.D.

Institut farmakologii im. V.V. Zakusova RAMN, Moskva

Bocharov E.V.

Institut farmakologii im. V.V. Zakusova RAMN, Moskva

Raevskiĭ K.S.

Institut normal'noĭ fiziologii im. P.K. Anokhina RAMN;
Institut farmakologii im. V.V. Zakusova RAMN, Moskva

Ugriumov M.V.

Institut biologii razvitiia im. N.K. Kol'tsova RAN, Moskva

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