Parkinson’s disease (PD) is characterized by slow progression with a long prodromal stage and the gradual evolution of both neuropsychological symptoms and subtle motor changes, preceding motor dysfunction. Thus, in order for animal models of PD to be valid, they should reproduce these characteristics of the disease. One of such models, in which neuropathology is induced by chronic injections of low doses of mitochondrial toxin rotenone, is well established in rats. However, data on this model adapted to mice remain controversial. We have designed the study to describe the timecourse of motor and non-motor symptoms during chronic subcutaneous administration of rotenone (4 mg/kg daily for 35 days) in C57BL/6 mice. We characterize the underlying neuropathological processes (dopaminergic neuron degeneration, regional brain metabolism, monoamine neurotransmitter and lipid peroxidation changes) at different timepoints: 1 day, 2 weeks and 5 weeks of daily rotenone exposure. Based on the behavioral data, we can describe three stages of pathology: cognitive changes from week 2 of rotenone exposure, subtle motor changes in week 3–4 and motor dysfunction starting roughly from week 4. Neuropathological changes in this model include a general decrease in COX activity in different areas of the brain (acute effect of rotenone) and a more specific decrease in midbrain (chronic effect), followed by significant neurodegeneration in SNpc but not VTA by the 5th week of rotenone exposure. However, we were unable to find changes in the level of monoamine neurotransmitters neither in the striatum nor in the cortex, nor in the level of lipid peroxidation in the brainstem. Thus, the gradual progression of pathology in this model is linked with metabolic changes, rather than with oxidative stress or tonic neurotransmitter release levels. Overall, this study supports the idea that a low-dose rotenone mouse model can also reproduce different stages of PD as well as rats.

Oxidative stress, accompanied by mitochondrial dysfunction, is a key mechanism involved in the pathogenesis of Parkinson’s disease (PD). Both carnosine and lipoic acid are potent antioxidants, the applicability of which in therapy is hindered by their limited bioavailability. This study aimed to evaluate the neuroprotective properties of a nanomicellar complex of carnosine and lipoic acid (CLA) in a rotenone-induced rat model of PD. Parkinsonism was induced via the administration of 2 mg/kg rotenone over the course of 18 days. Two doses of intraperitoneal CLA (25 mg/kg and 50 mg/kg) were administered alongside rotenone to assess its neuroprotective effect. At 25 mg/kg CLA decreased muscle rigidity and partially restored locomotor activity in animals that received rotenone. Furthermore, it caused an overall increase in brain tissue antioxidant activity, accompanied by a 19% increase in neuron density in the substantia nigra and increased dopamine levels in the striatum relative to animals that only received rotenone. Based on the acquired results, it may be concluded that CLA have neuroprotective properties and could potentially be beneficial in PD treatment when used in conjunction with the base therapy.

Parkinson’s disease is the second most common neurodegenerative movement disorder caused by the death of dopaminergic neurons in the Substantia nigra. The motor symptoms of Parkinson’s disease only become apparent in the late stages, whereas non-motor impairments often manifest earlier. Therefore, devising adequate experimental models to study the pathogenesis of Parkinson’s disease is of fundamental scientific importance. In this study, we aimed to evaluate the behavioral and neurochemical characteristics in a model of the premotor stage of parkinsonism in mice induced by chronic administration of a low dose of methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP. Administering 3 mg/kg of the toxin for 35 days does not cause motor deficits, except in fine motor skills, and results in impaired spatial learning. In addition, this stage is characterized by the depletion of striatum and prefrontal cortex dopamine, decreased tyrosine hydroxylase in striatum and Substantia nigra, increased cytochrome oxidase and superoxide dismutase expression, and microglia activation. Concluding, the presented model made it possible to identify a complex of physiological and neurochemical disorders characteristic of the early stage of Parkinsonism.

The review relates to modern point of view on the role of cerebellar structures in eye movement control. The review dedicates todisorders of all types of eye movements involving participating cerebellum in oculomotor and vestibular systems which are supported by experimental results. Revealing the mechanisms of eye movement disorders, especially when gaze-holding and saccadic movements, opens possibilities for its therapy.