The Treadmill Exercise Protects against Dopaminergic Neuron Loss and Brain Oxidative Stress in Parkinsonian Rats

Abstract

Parkinson's disease (PD), a progressive neurological pathology, presents motor and nonmotor impairments. The objectives were to support data on exercise benefits to PD. Male Wistar rats were distributed into sham-operated (SO) and 6-OHDA-lesioned, both groups without and with exercise. The animals were subjected to treadmill exercises (14 days), 24 h after the stereotaxic surgery and striatal 6-OHDA injection. Those from no-exercise groups stayed on the treadmill for the same period and, afterwards, were subjected to behavioral tests and euthanized for neurochemical and immunohistochemical assays. The data, analyzed by ANOVA and Tukey post hoc test, were considered significant for p < 0.05. The results showed behavioral change improvements in the 6-OHDA group, after the treadmill exercise, evaluated by apomorphine rotational behavior, open field, and rota rod tests. The exercise reduced striatal dopaminergic neuronal loss and decreased the oxidative stress. In addition, significant increases in BDNF contents and in immunoreactive cells to TH and DAT were also observed, in striata of the 6-OHDA group with exercise, relatively to those with no exercise. We conclude that exercise improves behavior and dopaminergic neurotransmission in 6-OHDA-lesioned animals. The increased oxidative stress and decreased BDNF contents were also reversed, emphasizing the importance of exercise for the PD management.

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

“…Moreover, in MPTP mice with 18 weeks of pretraining, Lau et al [126] showed protection of mitochondrial integrity and respiratory function in ST as compared to sedentary MPTP mice. In addition, da Costa group [133] also observed the drop in oxidative stress, which was measured as nitrite content and lipid peroxidation level.…”

“…Moreover, physical exercise increased spontaneous locomotor activity and subthreshold L-DOPA-induced activity [133] and decreased depressive-like behavior, measured as immobility, in open field test [131]. Furthermore, physical training decreased contralateral bias in cylinder test [127] and ipsilateral rotations in amphetamine-induced rotational test [127,134] and reduced rotational asymmetry in apomorphine-induced rotational test [128,131,133]. Additionally, the use of BDNF receptor inhibitor K252a reversed the protective effect of exercise on rotational bias [128].…”

“…BDNF production was shown to be stimulated by both voluntary [75] and forced physical activity [125][126][127][128][129][130][131][132][133]. BDNF upregulation was observed in midbrain [125], SN [126,128,129], ST [127,129,131,133], hippocampus [133], and cortex [132,133]. Tuon et al [131] reported an attenuated decline of proBDNF content in 6-OHDA-induced PD rats trained for 60 days before lesion.…”

“…In animal models of PD, exercise was able to increase the number of TH-ir neurons in SN [125][126][127][128][129][130]134], the TH protein level in SN [126,128] and ST [128,134], and TH-ir fiber intensity in ST [127,128]. Physical activity also led to a normalization of the DA content in SN and/or ST [75,126,129,130,132,133] and of 3,4-dihydroxyphenylacetic acid (DOPAC) level in ST [129,133], to a slight increase in the homovanillic acid (HVA) content in ST [133] and an elevation in the DAT level in ST [126,133]. HVA and DOPAC are DA metabolites, whereas DAT is responsible for DA reuptake from synapses.…”

“…In addition, it was shown that, in animal models of PD, training is able to improve motor performance, namely movement and balance on a balance beam [126] and motor memory in rotarod test [129,133]. Moreover, physical exercise increased spontaneous locomotor activity and subthreshold L-DOPA-induced activity [133] and decreased depressive-like behavior, measured as immobility, in open field test [131]. Furthermore, physical training decreased contralateral bias in cylinder test [127] and ipsilateral rotations in amphetamine-induced rotational test [127,134] and reduced rotational asymmetry in apomorphine-induced rotational test [128,131,133].…”