References for this Review were identified through searches of PubMed using the search terms “exercise” linked to “Parkinson's”, “neuroplasticity”, “environmental enrichment”, “dopamine”, “glutamate”, “synaptogenesis”, “striatum and physiology”, “basal ganglia”, and “physical activity”. We mainly selected papers published between Jan 1, 1998, and Dec 31, 2013, in English, but we did not exclude commonly referenced and highly regarded older publications. We also searched the reference list
ReviewExercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease
Introduction
Parkinson's disease is a progressive neurodegenerative disorder that is characterised by the loss of dopamine caused by degeneration of substantia nigra pars compacta dopaminergic neurons. Characteristic features of Parkinson's disease include motor impairment (bradykinesia, rigidity, tremor, gait dysfunction, and postural instability), cognitive impairment (frontal lobe executive dysfunction), and mood disorders. In healthy individuals, motor performance depends on the interaction between automatic (unconscious) and volitional (cognitive) control of movement.1, 2 Conversely, in Parkinson's disease, the early and preferential loss of dopamine in the caudal regions of the basal ganglia (dorsal regions in rodents) leads to diminished automatic and increased cognitive control of movements that include frontal lobe circuitry. Consequently, individuals with Parkinson's disease need to handle and sustain a larger cognitive load to execute either motor or cognitive (eg, working memory) tasks.2, 3 Dopamine replacement therapy alleviates some motor features of Parkinson's disease, but with less beneficial effects observed on cognitive function.4 In the past decade, mounting evidence has accumulated for the role of exercise in the improvement of motor performance, which might include facilitation of both the cognitive and automatic control of movement.
Epidemiological studies have supported a link between strenuous exercise and reduced risk for Parkinson's disease.5, 6 Additionally, many studies and published reviews on exercise in normal ageing and in Parkinson's disease provide the background that supports the benefits of exercise, physical activity, and environmental enrichment.7, 8, 9 Although research into exercise and Parkinson's disease is continuing, the overall purpose of this Review is to draw attention to published studies in human beings and animal models of Parkinson's disease that might support the beneficial effects of exercise through neuroplastic mechanisms. First, we introduce the notion that exercise, through goal-based and aerobic training, might enhance neuroplasticity, which is important for driving motor and cognitive behavioural improvement in Parkinson's disease. Second, we report findings from studies of animals that show the neuroprotective and neurorestorative capacity of intensive exercise. Finally, we present data on the potential role of exercise in overall brain health that might influence the structural (connectivity) and physiological properties of brain function.
Neuroplasticity is a process by which the brain encodes experiences and learns new behaviours and is defined as the modification of existing neural networks by addition or modification of synapses in response to changes in behaviour or environment, which can encompass exercise.10 Neuroplasticity includes a wide range of structural and physiological mechanisms including synaptogenesis, neurogenesis, neuronal sprouting, and potentiation of synaptic strength, all of which can lead to the strengthening, repair, or formation of neuronal circuitry.11 Importantly, exercise-induced benefits on brain health (ie, blood flow, trophic factors, and the immune system) might help to create the optimum milieu needed for neuroplasticity to happen in the injured brain. We highlight exercise approaches used to drive behavioural improvement in individuals with Parkinson's disease and findings in animal studies that support the potential for targeting neuroplasticity.
Section snippets
Goal-based exercise
Exercise is the general term for physical activity that is planned, structured, and repetitive for the purpose of conditioning any part of the body. In the past decade, an important direction in the specialty of neurorehabilitation and exercise research in Parkinson's disease has been the application of exercise that incorporates goal-based motor training for the improvement or recovery of impaired or lost motor function. This exercise approach can be termed goal based because it shares
Effects of exercise on cognition
The loss of dopamine in the basal ganglia not only affects automaticity but also impairs cognitive (executive) functions,59, 60 especially mental flexibility and set shifting related to alterations in frontostriatal connectivity.61, 62, 63 Cognition is affected early and progresses with disease severity and affects many neurotransmitter systems including dopaminergic, serotoninergic, noradrenergic, and cholinergic systems.64, 65 In addition to improvement of motor performance, aerobic exercise
Exercise studies in animal models of Parkinson's disease
Animal models provide an important method to investigate the mechanisms by which exercise induces neuroplasticity in the mammalian brain. Two commonly used models of dopamine depletion are the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model and the 6-hydroxydopamine (6-OHDA)-lesioned rat model.75 Both toxins lead to the destruction of nigrostriatal dopamine neurons and the subsequent depletion of dopamine in the dorsal striatum. Exercise improves motor performance,
Effects of exercise on brain health
Although exercise might have very targeted effects on specific basal ganglia circuits (eg, in corticostriatal neurotransmission through glutamate and its modulation by dopamine), exercise can also have more global effects on factors that influence general brain health. These include blood flow through vascularisation and angiogenesis, activation of beneficial effects of the immune system, induction of neurotrophic factors, and neurogenesis.99
Conclusions
In the past decade, a main focus of neurorehabilitation has been to alleviate the motor deficits of Parkinson's disease through exercise.10, 131 The general idea is that exercise that incorporates goal-based motor skill learning improves motor skill performance in Parkinson's disease and that this might be enhanced through cognitive engagement. Importantly, exercise that combines goal-based with aerobic training might work synergistically to promote automatic and volitional components of motor
Search strategy and selection criteria
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