1. Institute of Biomedical Chemistry, Moscow, Russia; Zakusov Institute of Pharmacology, Moscow, Russia 2. Institute of Biomedical Chemistry, Moscow, Russia
The neurotoxins rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (МPTP) are used for modeling Parkinson's disease in animals (PD). They induce the mitochondrial respiratory chain dysfunction, which leads to the dopaminergic (DA) neuron degeneration. The advantage of the rotenone model consists in ability of rotenone to cause neurodegeneration showing symptoms and molecular biological characteristics similar to those of PD. Isatin (indoldione-2,3) is an endogenous regulator found in tissues and biological fluids of humans and animals. It exhibits a broad range of biological activity mediated by numerous isatin-binding proteins. In this work we have investigated behavioral reactions and profiles of brain isatin-binding proteins of rats with Parkinson's syndrome (PS) in comparison with the corresponding parameters of MPTP-induced Parkinsonism in mice. Systemic injection of rotenone caused severe PS comparable with the effect of MPTP injection. It was accompanied by significant body weight loss, death, oligokinesia, muscular rigidity, and postural instability of animals. In spite of the same pathogenic basis of PS caused by rotenone and MPTP, the molecular mechanisms of their action differ. In the case of rotenone-induced PS, the pool of isatin-binding proteins common of the control rats and the rats with PS (146) significantly exceeded the pool of the common proteins of control mice and mice with PS induced by MPTP, whether right after neurotoxin injection (27), or (all the more) in a week after the MPTP injection (14). The comparison of isatin-binding proteins specific of the animals with MPTP-induced PS and with the rotenone-induced PS (as compared with the control animals) revealed total absence of proteins common of these two models of PD. It is to be noted that both neurotoxins particularly affected the proteins participating in the signal transmission and enzyme activity regulation. The changes of the profile of isatin-binding proteins in response to the injection of rotenone suggest that the neuroprotector isatin could also influence positively in the case of the rotenone model of PD.
Kapitsa I.G., Kazieva L.Sh., Vavilov N.E., Zgoda V.G., Kopylov A.T., Medvedev A.E., Buneeva O.A. (2023) Characteristics of behavioral reactions and the profile of brain isatin-binding proteins of rats with the rotenone-induced experimental parkinsonism. Biomeditsinskaya Khimiya, 69(1), 46-54.
Kapitsa I.G. et al. Characteristics of behavioral reactions and the profile of brain isatin-binding proteins of rats with the rotenone-induced experimental parkinsonism // Biomeditsinskaya Khimiya. - 2023. - V. 69. -N 1. - P. 46-54.
Kapitsa I.G. et al., "Characteristics of behavioral reactions and the profile of brain isatin-binding proteins of rats with the rotenone-induced experimental parkinsonism." Biomeditsinskaya Khimiya 69.1 (2023): 46-54.
Kapitsa, I. G., Kazieva, L. Sh., Vavilov, N. E., Zgoda, V. G., Kopylov, A. T., Medvedev, A. E., Buneeva, O. A. (2023). Characteristics of behavioral reactions and the profile of brain isatin-binding proteins of rats with the rotenone-induced experimental parkinsonism. Biomeditsinskaya Khimiya, 69(1), 46-54.
References
Duty S., Jenner P. (2011) Animal models of Parkinson's disease: A source of novel treatments and clues to the cause of the disease. Br. J. Pharmacol., 164(4),1357-1391. CrossRef Scholar google search
Fleming S.M., Zhu C., Fernagut P.O., Mehta A., Dicarlo C.D., Seaman R.L., Chesselet M.F. (2004) Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone. Exp. Neurol., 187(2), 418-429. CrossRef Scholar google search
Fleming S.M., Salcedo J., Fernagut P.O., Rockenstein E., Masliah E., Levine M.S., Chesselet M.F. (2004) Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein. J. Neurosci. 24, 9434-9440. CrossRef Scholar google search
Cannon J.R., Tapias V.M., Na H.M., Honick A.S., Drolet R.E., Greenamyre J.T. (2009) A highly reproducible rotenone model of Parkinson's disease. Neurobiol. Dis., 34(2), 279-290. CrossRef Scholar google search
Meredith G.E., Rademacher D.J. (2011) MPTP mouse models of Parkinson's disease: An update. J. Parkinsons Dis., 1(1), 19-33. CrossRef Scholar google search
Medvedev A., Igosheva N., Crumeyrolle-Arias M., Glover V. (2005) Isatin: Role in stress and anxiety. Stress, 8, 175-183. CrossRef Scholar google search
Medvedev A., Buneeva O., Glover V. (2007) Biological targets for isatin and its analogues: implications for therapy. Biologics, 1, 151-162. Scholar google search
Crumeyrolle-Arias M., Buneeva O., Zgoda V., Kopylov A., Cardona A., Tournaire M.C., Pozdnev V., Glover V., Medvedev A. (2009) Isatin binding proteins in rat brain: In situ imaging, quantitative characterization of specific [3H]isatin binding, and proteomic profiling. J. Neurosci. Res., 87, 2763-2772. CrossRef Scholar google search
Buneeva O., Gnedenko O., Zgoda V., Kopylov A., Glover V., Ivanov A., Medvedev A., Archakov A. (2010) Isatin binding proteins of rat and mouse brain: proteomic identification and optical biosensor validation. Proteomics, 10, 23-37. CrossRef Scholar google search
Medvedev A., Buneeva O., Gnedenko O., Ershov P., Ivanov A. (2018) Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications. Biofactors, 44(2), 95-108. CrossRef Scholar google search
Medvedev A., Kopylov A., Buneeva O., Kurbatov L., Tikhonova O., Ivanov A., Zgoda V.A. (2020) Neuroprotective dose of isatin causes multilevel changes involving the brain proteome: prospects for further research. Int. J. Mol. Sci., 21(11), 4187. CrossRef Scholar google search
Medvedev A., Buneeva O. (2022) Tryptophan metabolites as mediators of microbiota-gut-brain communication: Focus on isatin. A mini review. Front. Behav. Neurosci., 16, 922274. CrossRef Scholar google search
Buneeva O.A., Kopylov A.T., Nerobkova L.N., Kapitsa I.G., Zgoda V.G., Medvedev A.E. (2017) The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins. Biomeditsinskaya Khimiya, 63(4), 316-320. CrossRef Scholar google search
Medvedev A.E., Goodwin D.L., Sandler M., Glover V. (1999) Efficacy of isatin analogues as antagonists of rat brain and heart atrial natriuretic peptide receptors coupled to particulate guanylate cyclase. Biochem. Pharmacol., 57, 913-915. CrossRef Scholar google search
Voronina T.A., Seredenin S.B., Yarkova M.A., Voronin M.V. (2012) Rukovodstvo po provedeniyu doklinicheskih issledovanij lekarstvennyh sredstv, chast' pervaya. A.N. Mironov (ed.), Grif i K, Moskva, 994 p. Scholar google search
Khaing Z.Z., Geissler S.A., Schallert T., Schmidt C.E. (2013) Assessing forelimb function after unilateral cervical SCI using novel tasks: Limb step-alternation, postural instability and pasta handling. J.Vis. Exp., 79, e50955. CrossRef Scholar google search
Tillerson J.L., Miller G.W. (2003) Grid performance test to measure behavioral impairment in the MPTP-treated-mouse model of parkinsonism. J. Neurosci. Methods, 123(2), 189-200. CrossRef Scholar google search
Walker J.M. (ed.) (2002) The Protein Protocol Handbook, Humana Press Inc., Totowa, N.Y. Scholar google search
Wiśniewski J.R., Zougman A., Nagaraj N., Mann M. (2009) Universal sample preparation method for proteome analysis. Nat. Methods, 6(5), 359-362. CrossRef Scholar google search
Kapp E.A., Schütz F., Connolly L.M., Chakel J.A., Meza J.E., Miller C.A., Fenyo D., Eng J.K., Adkins J.N., Omenn G.S., Simpson R.J. (2005) An evaluation, comparison, and accurate benchmarking of several publicly available MS/MS search algorithms: Sensitivity and specificity analysis. Proteomics, 5(13), 3475-3490. CrossRef Scholar google search
Medvedev A.E., Buneeva O.A., Kopylov A.T., Tikhonova O.V., Medvedeva M.V., Nerobkova L.N., Kapitsa I.G., Zgoda V.G. (2017) Brain mitochondrial subproteome of Rpn10-binding proteins and its changes induced by the neurotoxin MPTP and the neuroprotector isatin. Biochemistry (Moscow), 82(3), 330-339. CrossRef Scholar google search