Run in the Light: Exploring Exercise and Photobiomodulation in Parkinson's Disease

Description

Parkinson's disease is a neurological disorder with cardinal motor signs of resting tremor, bradykinesia and lead-pipe rigidity. In addition, many patients display non-motor symptoms, including a diminished sensation of smell, gastrointestinal problems, various disorders of sleep and some cognitive impairment. These clinical features - particularly the motor signs - manifest after a progressive death of many dopaminergic neurones in the brain. Although currently available, conventional therapies can reduce the signs of the disease, the progression of this neuronal death has proved difficult to slow or stop, and the condition is relentlessly progressive. Hence, there is a real need to develop a treatment that is neuroprotective, one that slows the pathology of the disease effectively. At present, there are several neuroprotective therapies in the experimental pipeline, but these are for the patients of tomorrow. This book focuses on two therapies that are readily available for the patients of today. They involve the use of exercise and light (i.e. photobiomodulation, the use of red to infrared light therapy (λ=600-1070nm) on body tissues). The two therapies are tied together in several ways. First, in animal models of Parkinson's disease, they each have been shown to offer the key feature of neuroprotection, stimulating a series of built-in protective mechanisms within the neurones, that helps their survival, to self-protect and/or self-repair. There are also some promising indications of neuroprotection and many beneficial outcomes in parkinsonian patients. Further, both exercise and light therapies are similar in that they are non-invasive and safe to use, with no known adverse side-effects, making their combination with the conventional therapies, such as dopamine replacement drug therapy and deep brain stimulation, all the more feasible. Given the heterogeneity of Parkinson's disease in humans, tackling the condition from a range of different angles - with a number of different therapies - would only serve to enhance the positive outcomes. This book considers the use of exercise and light therapies, proposing that they have the potential to make a powerful "dynamic duo", offering a most effective neuroprotective treatment option to patients. PRELIMS.pdf Preface Acknowledgements Author biography John Mitrofanis Abbreviations CH001.pdf Chapter 1 Parkinson’s disease 1.1 General 1.2 Signs and symptoms 1.3 The basal ganglia 1.3.1 Basic structure, neurochemistry and connections 1.3.2 Overall functions of basal ganglia 1.3.3 The loops 1.3.4 The direct and indirect pathways 1.3.5 Summary 1.4 Pathophysiology 1.4.1 Zones of neuronal pathology 1.4.2 Lewy bodies and α-synuclein 1.4.3 Gliosis 1.4.4 Growth factors 1.4.5 Other pathological changes 1.4.6 Mechanisms of neuronal death 1.4.7 Neural circuits behind the signs and symptoms 1.4.8 Predictive tests 1.5 Risk factors 1.5.1 Age 1.5.2 Environmental toxin 1.5.3 Vascular 1.5.4 Head injury 1.5.5 Gender and race 1.5.6 Genetics 1.5.7 Summary 1.6 Animal models 1.6.1 Toxin-induced models 1.6.2 Transgenic models 1.6.3 Summary 1.7 Current treatments 1.7.1 Dopamine replacement drug therapy 1.7.2 Surgical treatment: deep brain stimulation at high frequency 1.8 Neuroprotection and future treatments 1.8.1 Neuroprotection basics 1.8.2 Neuroprotective versus symptomatic treatments? 1.8.3 Why no neuroprotective treatment for patients? 1.8.4 Future treatments 1.8.5 Summary References CH002.pdf Chapter 2 The run is exercise 2.1 General 2.2 Why should exercise work? 2.3 How much exercise do you need? 2.4 Methods of exercise: how do you do it? 2.5 Exercise-induced neuroprotection: a matter of survival 2.5.1 Evidence for exercise-induced neuroprotection in animal models of Parkinson’s disease 2.5.2 Is there exercise-induced neuroprotection in Parkinson’s disease patients? 2.5.3 How does exercise neuroprotect: the mechanisms 2.6 Exercise-induced symptomatic effects: a matter of function 2.6.1 Evidence for exercise-induced changes in function in the brain 2.6.2 How does exercise influence neuronal function? 2.7 Exercise-induced functional and behavioural improvements 2.7.1 Evidence for functional and behavioural changes in animal models of Parkinson’s disease 2.7.2 Evidence for clinical effects in Parkinson’s disease patients 2.7.3 Factors that generate exercise-induced functional and behavioural changes: neuroprotective or symptomatic? 2.8 Summary and a working hypothesis for a ‘trigger’ 2.8.1 What is the trigger? References CH003.pdf Chapter 3 The light is photobiomodulation 3.1 General: what is light? 3.1.1 The light (photobiomodulation) and its history 3.1.2 Neural applications of light 3.1.3 Light sources, wavelengths, powers and modes 3.1.4 How far does light travel? 3.1.5 Is light safe? 3.1.6 Other light wavelengths 3.2 Light-induced neuroprotection: a matter of survival 3.2.1 Evidence for light-induced neuroprotection in animal models of Parkinson’s disease 3.2.2 How does light neuroprotect: the mechanisms 3.3 Light-induced symptomatic effects: a matter of function 3.3.1 Evidence for light-induced changes in brain function 3.3.2 How does light influence neuronal function? 3.4 Light-induced functional and behavioural improvements in animal models of Parkinson’s disease 3.4.1 Evidence for functional and behavioural changes in animal models of Parkinson’s disease 3.4.2 Factors that generate light-induced functional and behavioural changes: neuroprotective or symptomatic? 3.5 How will light work in humans? 3.6 Light-induced changes in Parkinson’s disease patients 3.6.1 Light application in other diseases and systems 3.7 The road to a therapeutic option for light treatment in patients 3.8 Why should light work? 3.9 Summary References CH004.pdf Chapter 4 The run and the light: the dynamic duo 4.1 They are so similar 4.1.1 Animal models 4.1.2 Patients 4.1.3 Do exercise and light use common mechanisms for two outcomes? 4.2 Potential benefits of a combined therapy: a cocktail 4.3 Is there a precedent? 4.3.1 Exercise plus light therapy in animal studies 4.3.2 Exercise plus light therapy in humans 4.3.3 Summary 4.4 A combined therapy protocol for Parkinson’s disease patients? 4.4.1 Light wavelength, dosage and application site 4.4.2 Exercise programme 4.4.3 Timing of light application in relation to exercise 4.4.4 What about eating more vegetables? 4.4.5 Summary 4.5 Conclusions References