No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23757号 / 医博第4803号 / 新制||医||1056(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 井上 治久, 教授 岩田 想, 教授 上杉 志成 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Movement problems related to Parkinson’s disease (PD) have been shown to have a profound effect on functional independence and reported quality of life. Within the constellation of movement signs of PD (tremor, muscle rigidity, bradykinesia/hypokinesia, and postural instability), impaired arm swing is often the earliest-recognized symptom. It is also a strong independent predictor of greater fall risk and morbidity/mortality risk. Early treatment for movement problems such as impaired arm swing is associated with the greatest improvement in these impairments. However, movement problems often coincide with impaired processing of sensory information, leaving many people with PD with inadequate awareness of their posture and limb position. Thus, PD-related gait deficits are difficult for people to correct by themselves. External cueing techniques (such as visual cues in the environment or auditory cues for pacing and rhythm) have shown promise in improving parameters such as gait speed, s / Kinesiology

The purposes of this study were: (1) to determine whether there was a correlation between a quantitative assessment of postural sway , and a clinical assessment of postural stability, in patients diagnosed with idiopathic Parkinson's disease (PD); (2) to plot individual diurnal changes in postural sway characteristics of PD patients over an eight-hour time period; (3) to plot day to day changes in individual postural sway characteristics of PD patients: (4) to determine whether there was a difference in the postural sway characteristics of parkinsonians, with and without vision; (5) to determine whether there was a difference in the postural sway characteristics of the same individuals when using either Sinemet or Oeprenyl. Three male PD patients were recruited into this study. Each subject stood on a stable force platform (AMT1 OR6-5-1). Measurements included the standard deviations of the coordinates of the centre of pressure (COP) in the anterior-posterior (a-p) and lateral (lat) directions, the mean velocity of sway, and area of sway. These dependent measures were evaluated in a "quiet standing" condition, once with the eyes open (EO) and once with the eyes closed (EC). These procedures were carried out ten times over the course of an eight hour day. Each subject was tested two days while taking eight hour day. Each subject was tested two days while taking Sinemet, and two days while on the Deprenyl regimen. Secondly, at two periods of each test day, each patient was evaluated using the postural assessment section of the Sears Parkinson's Assessment Form (SPAF). The results were: (1) group analyses and individual analyses established the evidence of significant correlations between both the quantitative measures of postural sway (force platform) and the qualitative assessment tool (SPAF): (2) significant variability was evident in the analysis of individual data plots: (3) no statistically significant differences were observed tor any subject when measured from day to day; (4) generally, vision was a stabilizing factor in postural control, however, this was quite variable for each subject; (5) significant improvements in postural stability were observed with the introduction of Deprenyl for one out of three subjects. These findings are discussed in terms of their clinical and behavioral importance, with specific reference to Physiotherapy. / Thesis / Master of Science (MS)

Disorders of the central nervous system (CNS) continuously pose problems for current therapeutics. In part, this is due to the uncertainty of underlying pathophysiological changes that give rise to specific disorders. Parkinson’s disease (PD) specifically is a neurodegenerative CNS disorder with unknown origins of dopaminergic degeneration in the substantia nigra. Current therapies are reactive in nature and no existing neuroprotective therapies are available. Two hypotheses have been proposed to contribute to dopaminergic degeneration in PD: endoplasmic reticulum (ER) stress and oxidative stress. This thesis investigates molecular targets involved in each of these responses (mesencephalic astrocyte-derived neurotrophic factor (MANF) and cyclin-dependent 5 (CDK5)/p25 respectively) to support a multi-hit hypothesis in PD neural degeneration. Using behavioural and biochemical analysis, a reduction in MANF was found to participate in the ER stress hypothesis and CDK5/p25 hyperactivation is a viable neuroprotective target related to the oxidative stress hypothesis. Both pathways are evidenced in PD pathology and this thesis proposes specific targets for both pathways in the development of necessary neuroprotective therapies. Subsequently, included in this thesis is a chapter about the unmet pharmacological alleviation of negative and cognitive symptom domains in another CNS disorder of unknown pathophysiology: schizophrenia (SZ). These untreated symptoms are thought to be caused by irregularities in the signalling of multiple neurotransmitter systems. This chapter investigates the role of synapsin II, a protein involved in regulating signalling of multiple neurotransmitters, in manifesting negative and cognitive SZ symptoms and analyzes brain glucose metabolism. Reduced synapsin II levels were consistently implicated in the underlying physiology, and therefore synapsin II is proposed as a potential pharmacological target for these unmedicated symptomologies. Overall this thesis uses interrelated studies to propose novel molecular targets to address unmet therapeutic needs based on evidence of their involvement in the pathophysiology of PD and SZ. / Thesis / Doctor of Philosophy (PhD) / Brain diseases like Parkinson’s disease (PD) and Schizophrenia (SZ) are difficult to treat because their cause has not been discovered. PD shows degeneration of cells in the brain but the cause for degeneration is unknown. This makes developing treatments to protect cells from dying difficult. Two pathways are suggested to cause cell death in PD. This thesis proposes that both pathways are responsible for degeneration through a combined effort. Here, both pathways are shown to lead to cell death resembling PD and specific molecules are suggested as targets for developing protective treatments. Like PD, SZ has symptoms that cannot be treated because the cause is unclear. A protein was investigated for producing SZ-like symptoms and found to have potential for treatment design. This thesis aims to understand molecular changes in the brain leading to PD, with a look at SZ and how they can be used for better treatment design.