Effects of mitochondrial antioxidant SkQ1 on biochemical and behavioral parameters in a Parkinsonism model in mice

Biochemistry (Moscow) - Tập 82 - Trang 1513-1520 - 2017
V. V. Pavshintsev1,2, L. S. Podshivalova2, O. Y. Frolova1, M. V. Belopolskaya1, O. A. Averina2, E. A. Kushnir1, N. V. Marmiy1, M. L. Lovat1,2
1Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia
2Lomonosov Moscow State University, Faculty of Biology, Moscow, Russia

Tóm tắt

According to one hypothesis, Parkinson’s disease pathogenesis is largely caused by dopamine catabolism that is catalyzed on mitochondrial membranes by monoamine oxidase. Reactive oxygen species are formed as a byproduct of these reactions, which can lead to mitochondrial damage followed by cell degeneration and death. In this study, we investigated the effects of administration of the mitochondrial antioxidant SkQ1 on biochemical, immunohistochemical, and behavioral parameters in a Parkinson-like condition caused by protoxin MPTP injections in C57BL/6 mice. SkQ1 administration increased dopamine quantity and decreased signs of sensory-motor deficiency as well as destruction of dopaminergic neurons in the substantia nigra and ventral tegmental area in mice with the Parkinson-like condition.

Tài liệu tham khảo

Delaville, C., Deurwaerdere, P., and Benazzouz, A. (2011) Noradrenaline and Parkinson’s disease, Front. Syst. Neurosci., doi: 10.3389/fnsys.2011.00031. Richardson, J. R., Ananya, R., Shalat, S. L., Buckley, B., Winnik, B., Gearing, M., Levey, A. I., O’Suilleabhain, P., and German, D. C. (2011) Hexachlorocyclohexane levels in serum and risk of Parkinson’s disease, Neurotoxicology, 32. Langston, J. W. (2002) Parkinson’s disease: current and future challenges, Neurotoxicology, 23, 443–450. Edmondson, D. E., Binda, C., and Mattevi, A. (2007) Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B, Arch. Biochem. Biophys., 464, 269–276. Przedborski, S., Naini Ali, B., and Akram, M. (2001) The Parkinson toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydopyridine (MPTP): a technical review of its utility and safety, J. Neurochem., 76, 1265–1274. Dorszewska, J., Florczak, J., Rozycka, A., Kempisty, B., Jaroszewska-Kolecka, J., Chojnacka, K., Trzeciak, W. H., and Kozubski, W. (2007) Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer’s and Parkinson’s diseases, Acta Neurobiol. Exp., 67, 113–129. Garrido, A., Aldecoa, I., Gelpi, E., and Tolosa, E. (2017) Aggregation of a-synuclein in the gonadal tissue of 2 patients with Parkinson disease, JAMA Neurol., 74, 606–607. Cassarino, D. S., Parks, J. K., Parker, W. D., and Bennett, J. P. (1999) The parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism, Biochim. Biophys. Acta, 1453, 49–62. Ukraintseva, Y. S., Shchegolevskii, N. V., Korshunov, V. A., Kucheryanu, V. G., Ugryumov, M. V., and Bazya, A. S. (2010) Modeling of the presymptomatic stage of parkinsonism in mice: analysis of dopamine release in the striatum, Neurochem. J., 4, 142–147. Cohen-Kerem, R., and Koren, G. (2003) Antioxidants and fetal protection against ethanol teratogenicity. Review of the experimental data and implications to humans, Neurotoxicol. Teratol., 25, 1–9. Skulachev, V. P., Bogachev, A. V., and Kasparinskiy, F. O. (2010) Membrane Bioenergetics [in Russian], MSU, Moscow, pp. 269–321. Skulachev, V. P. (2012) Mitochondria-targeted antioxidants as promising drugs for treatment of age-related brain diseases, Alzheimer’s Dis., 28, 283–289. Ghosh, A., Chandran, K., Kalivendi, S. V., Joseph, J., Antholine, W. E., Hillard, C. J., Kanthasamy, A., Kanthasamy, A., and Kalyanaraman, B. (2010) Neuroprotection by a mitochondria-targeted drug in a Parkinson’s disease model, Free Radic. Biol. Med., 49, 1674–1684. Snow, B. J., Rolfe, F. L., Lockhart, M. M., Frampton, C. M., O’Sullivan, J. D., Fung, V., Smith, R. A., Murphy, M. P., and Taylor, K. M. (2010) A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson’s disease, Mov. Disord., 25, 1670–1674. Skulachev, V. P. (2009) An attempt to prevent senescence: a mitochondrial approach, Biochim. Biophys. Acta, 1787, 437–461. Lukashev, A. N., Skulachev, M. V., Ostapenko, V., Savchenko, A. Y., Pavshintsev, V. V., and Skulachev, V. P. (2014) Advances in development of rechargeable mitochondrial antioxidants, Prog. Mol. Biol. Transl. Sci., 127, 251–265. Deacon, M. J., and Rawlins, P. N. (2006) T-maze alternation in the rodent, Nat. Protocols, 1, 7–12. Pellow, S., Chopin, P., File, S. E., and Briley, M. (1985) Validation of open: closed arm entries in an elevated plusmaze as a measure of anxiety in the rat, J. Neurosci. Methods, 14, 149–167. File, S. E., and Wardill, G. (1975) The reliability of the hole-board apparatus, Psychopharmacologia, 44, 47–51. Schallert, T., Cenci, M. A., and Whishaw, I. Q. (2002) Animal models of neurological deficits: how relevant is the rat? Nat. Rev. Neurosci., 3, 574–579. Jackson-Lewis, V., and Przedborski, S. (2007) Protocol for the MPTP mouse model of Parkinson’s disease, Nat. Protocols, 2, 141–151. Feng, G., Zhang, Z., Bao, Q., Zhang, Z., Zhou, L., Jiang, J., and Li, S. (2014) Protective effect of chinonin in MPTP-induced C57BL/6 mouse model of Parkinson’s disease, Biol. Pharm. Bull., 37, 1301–1307. Nagarajan, S., Chellappan, D. R., Chinnaswamy, P., and Thulasingam, S. (2015) Ferulic acid pretreatment mitigates MPTP-induced motor impairment and histopathological alterations in C57BL/6 mice, Pharm. Biol., 53, 1591–1601. Zhu, Y., Zhang, J., and Zeng, Y. (2012) Overview of tyrosine hydroxylase in Parkinson’s disease, CNS Neurol. Disord. Drug Targets, 11, 350–358. Yang, W., Chen, Y. H., Liu, H., and Qu, H. D. (2015) Neuroprotective effects of piperine on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease mouse model, Int. J. Mol. Med., 36, 1369–1376. Sagi, Y., Mandel, S., Amit, T., and Youdim, M. B. (2007) Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism, Neurobiol. Dis., 25, 35–44.