Comparison of Neurobehavioral Changes in Mice Treated with Mitochondrial Toxins—Rotenone and MPTP

• Published in: Human physiology 2021-12, Vol.47 (8), p.821-830
• Main Authors: Berezhnoy, D. S., Troshev, D. V., Kulikova, O. I., Abaimov, D. A., Muzychuk, O. A., Stvolinsky, S. L., Fedorova, T. N.
• Format: Article
• Language: English
• Subjects: Antioxidants; Basal ganglia; Biomedical and Life Sciences; Biomedicine; Central nervous system diseases; Cytochrome c; Dopamine receptors; Electron transport chain; Human Physiology; Life Sciences; Mitochondria; Movement disorders; MPTP; Neostriatum; Neurodegeneration; Neurotoxins; Rotenone; Serotonin; Toxins
• ISSN: 0362-1197; 1608-3164
• DOI: 10.1134/S036211972108003X

In this study, the effects of chronic administration of low doses of the mitochondrial neurotoxins MPTP (4 mg/kg for 23 days) and rotenone (4 mg/kg for 7 days) in CD-1 mice were compared. A comparative assessment of neurochemical and behavioral changes at the pre-symptomatic stage of parkinsonism is given in these two different models side-by-side. We identified distinct motor and postural disorders in mice on the 23rd day of experiments when the animals received a total MPTP dose of 92 mg/kg. In animals treated with rotenone, similar motor disorders developed more rapidly, manifesting themselves by the 7th day of the experiment, when the cumulative administered dose was 28 mg/kg. The present study focused on the dynamics of neurochemical changes which precede the onset of motor symptoms: in MPTP-treated mice up to the 23rd day and in rotenone-treated mice up to the 7th day. We showed the similar dynamics of neurodegeneration in the SNpc—the rapid decrease in the number of neurons during the first 7 days in MPTP-treated mice (by 36%) and rotenone-treated mice (by 43%). However, Rotenone, unlike MPTP, did not cause a decrease in striatal dopamine levels by the time of motor impairments. This reveals a key difference in the effects of these toxins on the dopaminergic system. A transient increase in the serotonin content in the striatum of mice at the early stages of rotenone administration was noted. A significant decrease in endogenous antioxidant activity was observed as a side effect of both toxins, in line with the duration of toxin administration. Histochemical analysis revealed the different time dynamics of cytochrome-c-oxidase activity decrease, with more early and pronounced effects in the MPTP-treated mice. Based on the acquired results it can be concluded that MPTP, used at low doses, is a more reliable neurotoxin when compared to rotenone in inducing progressive nigrostriatal lesion and pre-symptomatic parkinsonism. Despite them both targeting the electron transport chain, the mechanisms behind their systemic action differ.