Depression in Parkinson\u27s disease: Perspectives from an Australian cohort

Introduction: Depression is often an under-recognised feature of Parkinson\u27s disease (PD). It is detrimental to physical and interpersonal functioning, negatively impacting a patient\u27s clinical management, quality of life and well-being. We aimed to identify clinical predictors and management implications of depression in Australian PD patients. Methods: 103 PD and 81 Healthy Control (HC) subjects were evaluated using the Beck Depression Inventory (BDI) and other validated PD motor and non-motor symptom (NMS) tools. Results: Nearly twice as many PD patients were depressed, (38.9% vs 20.1%, p = 0.009), with a corresponding increase in depression severity on the BDI (11.9; standard deviation (SD) 8.8 vs 5.2; SD 5.5, p\u3c0.001), and an odds ratio of 2.4 (95% confidence interval 1.2 - 4.7). Employment appeared to be a relative protective factor for depression, whilst patients requiring support services seemed to be more vulnerable to depression. Rapid Eye Movement Sleep Behaviour Disorder, dyskinesias, impulse control disorder, higher daily levodopa equivalent dose, increased motor severity, as well as catechol-O-methyltransferase inhibitor and amantadine use, all showed associations with depression (p\u3c0.05). Chronic pain, decreased physical activity, constipation and upper gastrointestinal dysfunction presented with an apparent increase in risk for developing depression and increased depression severity. Other NMS were also found to be associated with PD-related depression. Limitations: Potential selection bias of self-reporting data collection from specialist PD clinics in a single metropolitan area. Conclusion: Our findings provide novel insight into the prevalence of depression in PD, possible contributory factors and future treatment strategies targeting depression in PD

Gastrointestinal dysfunction in Parkinson\u27s disease

Background: Gastrointestinal (GI) dysfunction is prevalent in Parkinson’s disease (PD). Symptoms are evident throughout the disease course, affect the length of the GI tract and impact on patient quality of life and management. We clarify real-life differences in the frequency and severity of GI symptoms in a cohort of PD and healthy control (HC) subjects. Methods: 103 PD patients were compared to 81 HC subjects. Outcome measures collected from validated questionnaires included constipation severity, upper and lower GI symptoms and physical activity. Results: PD patients were three-times more likely to experience constipation than HC subjects, (78.6% vs 28.4%), exhibited a fourfold increase in constipation severity and formed harder stools. PD patients also reported increased symptoms of indigestion, nausea, excessive fullness and bloating, compared to the HCs. A higher mean Leeds Dyspepsia Questionnaire score for PD patients (8.3 (standard deviation (SD) 7.7) vs 4.6 (SD 6.1), p=0.001)) indicated increased symptom severity. Chronic pain was more frequently reported and correlated with constipation and upper GI dysfunction, being more prevalent and severe in women. Physical activity was notably decreased in the PD cohort (1823.6 (±1693.6) vs 2942.4 (±2620.9) metabolic equivalent-minutes/week, p=0.001) and correlated with constipation severity. PD therapies were associated with increased fullness and bloating and harder stools. Conclusions: PD patients report more prevalent and severe GI dysfunction, although our cohort comprised of many later stage participants. Earlier recognition of GI dysfunction in PD provides the opportunity to direct treatment for chronic pain and constipation, promote physical activity and rationalise PD therapies for optimal patient care

Reduced acetylated α-tubulin in SPAST hereditary spastic paraplegia patient PBMCs

HSP-SPAST is the most common form of hereditary spastic paraplegia (HSP), a neurodegenerative disease causing lower limb spasticity. Previous studies using HSP-SPAST patient-derived induced pluripotent stem cell cortical neurons have shown that patient neurons have reduced levels of acetylated α-tubulin, a form of stabilized microtubules, leading to a chain of downstream effects eventuating in increased vulnerability to axonal degeneration. Noscapine treatment rescued these downstream effects by restoring the levels of acetylated α-tubulin in patient neurons. Here we show that HSP-SPAST patient non-neuronal cells, peripheral blood mononuclear cells (PBMCs), also have the disease-associated effect of reduced levels of acetylated α-tubulin. Evaluation of multiple PBMC subtypes showed that patient T cell lymphocytes had reduced levels of acetylated α-tubulin. T cells make up to 80% of all PBMCs and likely contributed to the effect of reduced acetylated α-tubulin levels seen in overall PBMCs. We further showed that mouse administered orally with increasing concentrations of noscapine exhibited a dose-dependent increase of noscapine levels and acetylated α-tubulin in the brain. A similar effect of noscapine treatment is anticipated in HSP-SPAST patients. To measure acetylated α-tubulin levels, we used a homogeneous time resolved fluorescence technology-based assay. This assay was sensitive to noscapine-induced changes in acetylated α-tubulin levels in multiple sample types. The assay is high throughput and uses nano-molar protein concentrations, making it an ideal assay for evaluation of noscapine-induced changes in acetylated α-tubulin levels. This study shows that HSP-SPAST patient PBMCs exhibit disease-associated effects. This finding can help expedite the drug discovery and testing process

New insights into the complex role of mitochondria in Parkinson's disease

New discoveries providing insights into mitochondrial bioenergetics, their dynamic interactions as well as their role in cellular homeostasis have dramatically advanced our understanding of the neurodegenerative process of Parkinson's disease (PD). Respiratory chain impairment is a key feature in sporadic PD patients and there is growing evidence that links proteins encoded by PD-associated genes to disturbances in mitochondrial function. Against the backdrop of latest advances in the development of PD treatments that target mitochondria, we aim to give an overview of the literature published in the last three decades on the significance of mitochondria in the pathogenesis of PD. We describe the contribution of mitochondrial genome alterations and PD-associated genes to mitochondrial maintenance. We highlight mitophagy as a key mechanism in neurodegeneration. Moreover, we focus on the reciprocal interaction between alpha-synuclein aggregation and mitochondrial dysfunction. We discuss a novel trafficking pathway involving mitochondrial-derived vesicles within the context of PD and provide a synopsis of the most recently emerging topics in PD research with respect to mitochondria. This includes the relationship between mitochondria and cell-mediated immunity, the ER-mitochondria axis, sirtuin-mediated mitochondrial stress response and the role of micro RNAs in the aetiology of PD. In addition, recent studies have challenged the neuro-centric view of PD pathology, moving microglia and astrocytes into the research spotlight. Greater insights into these mechanisms may hold the key for the development of novel targeted therapies, addressing the need for a disease-modifying treatment, which has remained elusive to date

Parkinson\u27s disease and the gastrointestinal microbiome

Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and Parkinson’s disease (PD) and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of α-synuclein aggregates from the enteric nervous system to the brain. Here, we review evidence linking GM changes with PD, highlighting mechanisms supportive of pathological α-synuclein spread and intestinal inflammation in PD. We summarise existing patterns and correlations seen in clinical studies of the GM in PD, together with the impacts of non-motor symptoms, medications, lifestyle, diet and ageing on the GM. Roles of GM modulating therapies including probiotics and faecal microbiota transplantation are discussed. Encouragingly, alterations in the GM have repeatedly been observed in PD, supporting a biological link and highlighting it as a potential therapeutic target

Conflicts and configurations in a liminal space: SoTL scholars’ identity development

Although academic identity has received attention in the literature, there have been few attempts to understand the influence on identity from engagement with the Scholarship of Teaching and Learning (SoTL). In this aper, we (a group of eight scholars from five different countries) describe how our interactions with SoTL have impacted the shaping of our academic identities. We have struggled to define the value, purpose, outcomes, and meanings of being a disciplined SoTL scholar, sometimes in addition to and sometimes in opposition to being a disciplinary scholar. Through analysis of our own 100-word reflective narratives, we identify common conflicts and configurations around our experiences of developing a SoTL identity. We describe how navigating among conflicting identities can lead us into a troublesome but deeply reflective liminal space, prompting profound realizations and the reconstruction of academic identity. Drawing on this notion of liminality helps us to understand our journeys as moving through a necessary and important transformational landscape, and allows us to suggest ways to support those engaging with SoTL to develop an integrative SoTL identity

Mutant Parkin Impairs Mitochondrial Function and Morphology in Human Fibroblasts

Background: Mutations in Parkin are the most common cause of autosomal recessive Parkinson disease (PD). The mitochondrially localized E3 ubiquitin-protein ligase Parkin has been reported to be involved in respiratory chain function and mitochondrial dynamics. More recent publications also described a link between Parkin and mitophagy.Methodology/Principal Findings: In this study, we investigated the impact of Parkin mutations on mitochondrial function and morphology in a human cellular model. Fibroblasts were obtained from three members of an Italian PD family with two mutations in Parkin (homozygous c.1072delT, homozygous delEx7, compound-heterozygous c.1072delT/delEx7), as well as from two relatives without mutations. Furthermore, three unrelated compound-heterozygous patients (delEx3-4/duplEx7-12, delEx4/c.924C>T and delEx1/c.924C>T) and three unrelated age-matched controls were included. Fibroblasts were cultured under basal or paraquat-induced oxidative stress conditions. ATP synthesis rates and cellular levels were detected luminometrically. Activities of complexes I-IV and citrate synthase were measured spectrophotometrically in mitochondrial preparations or cell lysates. The mitochondrial membrane potential was measured with 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide. Oxidative stress levels were investigated with the OxyBlot technique. The mitochondrial network was investigated immunocytochemically and the degree of branching was determined with image processing methods. We observed a decrease in the production and overall concentration of ATP coinciding with increased mitochondrial mass in Parkin-mutant fibroblasts. After an oxidative insult, the membrane potential decreased in patient cells but not in controls. We further determined higher levels of oxidized proteins in the mutants both under basal and stress conditions. The degree of mitochondrial network branching was comparable in mutants and controls under basal conditions and decreased to a similar extent under paraquat-induced stress.Conclusions: Our results indicate that Parkin mutations cause abnormal mitochondrial function and morphology in non-neuronal human cells

Seeing the way: visual sociology and the distance runner's perspective

Employing visual and autoethnographic data from a two‐year research project on distance runners, this article seeks to examine the activity of seeing in relation to the activity of distance running. One of its methodological aims is to develop the linkage between visual and autoethnographic data in combining an observation‐based narrative and sociological analysis with photographs. This combination aims to convey to the reader not only some of the specific subcultural knowledge and particular ways of seeing, but also something of the runner's embodied feelings and experience of momentum en route. Via the combination of narrative and photographs we seek a more effective way of communicating just how distance runners see and experience their training terrain. The importance of subjecting mundane everyday practices to detailed sociological analysis has been highlighted by many sociologists, including those of an ethnomethodological perspective. Indeed, without the competence of social actors in accomplishing these mundane, routine understandings and practices, it is argued, there would in fact be no social order

Sheep Updates 2006 - part 3

This session covers six papers from different authors: GRAZING 1. Making better use of clover, Karen Venning and Andrew Thompson, Department of Primary Industries, Victoria 2. Grazing systems demonstration to optimise pasture utilisation and stocking rate, Mike Hyder, Sue-Ellen Shaw, Kelly Hill and Ron McTaggart, Department of Agriculture and Food Western Australia. 3. Know your audience to increase their rate of practice change - Lifetime Wool as an example, Gus Rose, Department of Agriculture and Food Western Australia, Carolyn Kabore, Kazresearch REPRODUCTION 4. Lifetime Wool - Ewe Management Guidlines, Mandy Curnow, Department of Agriculture and Food Western Australia 5. Achieving the best reproductive performance from your hoggets, Kenyon PR, Morris ST, West DM, Perkins NR, Pinchbeck GL., Institute of Veterinary, Animal and Biomedical Sciences, Massey University, New Zealand. 6. Lifetime Wool: Twin futures, Dr Ralph Behrendt, Department of Primary Industries, Victori