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

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          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.

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          Most cited references47

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          Malondialdehyde determination as index of lipid peroxidation.

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            Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis.

            Parkinson disease (PD) is associated with progressive loss of dopaminergic neurons in the substantia nigra, as well as with more-widespread neuronal changes that cause complex and variable motor and nonmotor symptoms. Recent rapid advances in PD genetics have revealed a prominent role for mitochondrial dysfunction in the pathogenesis of the disease, and the products of several PD-associated genes, including SNCA, Parkin, PINK1, DJ-1, LRRK2 and HTR2A, show a degree of localization to the mitochondria under certain conditions. Impaired mitochondrial function is likely to increase oxidative stress and might render cells more vulnerable to this and other related processes, including excitotoxicity. The mitochondria, therefore, represent a highly promising target for the development of disease biomarkers by use of genetic, biochemical and bioimaging approaches. Novel therapeutic interventions that modify mitochondrial function are currently under development, and a large phase III clinical trial is underway to examine whether high-dose oral coenzyme Q10 will slow disease progression. In this Review, we examine evidence for the roles of mitochondrial dysfunction and increased oxidative stress in the neuronal loss that leads to PD and discuss how this knowledge might further improve patient management and aid in the development of 'mitochondrial therapy' for PD.
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              Does vigorous exercise have a neuroprotective effect in Parkinson disease?

              J. Ahlskog (2011)
              Parkinson disease (PD) is progressive, with dementia and medication-refractory motor problems common reasons for late-stage nursing-home placement. Increasing evidence suggests that ongoing vigorous exercise/physical fitness may favorably influence this progression. Parkinsonian animal models reveal exercise-related protection from dopaminergic neurotoxins, apparently mediated by brain neurotrophic factors and neuroplasticity (predicted from in vitro studies). Similarly, exercise consistently improves cognition in animals, also linked to enhanced neuroplasticity and increased neurotrophic factor expression. In these animal models, immobilization has the opposite effect. Brain-derived neurotrophic factor (BDNF) may mediate at least some of this exercise benefit. In humans, exercise increases serum BDNF, and this is known to cross the blood-brain barrier. PD risk in humans is significantly reduced by midlife exercise, documented in large prospective studies. No studies have addressed whether exercise influences dementia risk in PD, but exercised patients with PD improve cognitive scores. Among seniors in general, exercise or physical fitness has not only been associated with better cognitive scores, but midlife exercise significantly reduces the later risk of both dementia and mild cognitive impairment. Finally, numerous studies in seniors with and without dementia have reported increased cerebral gray matter volumes associated with physical fitness or exercise. These findings have several implications for PD clinicians. (1) Ongoing vigorous exercise and physical fitness should be highly encouraged. (2) PD physical therapy programs should include structured, graduated fitness instruction and guidance for deconditioned patients with PD. (3) Levodopa and other forms of dopamine replenishment therapy should be utilized to achieve the maximum capability and motivation for patients to maintain fitness.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2017
                21 June 2017
                : 2017
                : 2138169
                Affiliations
                1Faculty of Medicine of the Federal University of Ceará (UFC), Fortaleza, CE, Brazil
                2Faculty of Medicine Estácio of Juazeiro do Norte (Estácio/FMJ), Juazeiro do Norte, CE, Brazil
                Author notes
                *Glauce Socorro de Barros Viana: gbviana@ 123456live.com

                Academic Editor: Rodrigo Franco

                Author information
                http://orcid.org/0000-0002-2366-4024
                http://orcid.org/0000-0002-9996-9537
                Article
                10.1155/2017/2138169
                5497606
                28713483
                96c18d87-fc63-4247-bdd4-3dbc7c91b9d6
                Copyright © 2017 Roberta Oliveira da Costa et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 February 2017
                : 23 April 2017
                : 26 April 2017
                Funding
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico
                Funded by: Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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