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General Information | ||||||||||||
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Brain Bank Bulletin |
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1. So Many QuestionsThe Tissue Bank have recently sent out two questionnaires to our prospective donors. The first concerns the medical history, including all drug treatments, acute and chronic conditions and further details relating to dietary, occupational and family background. The second questionnaire, which is to be sent out at regular intervals to those enrolled in our donorship scheme, contains 100 questions which address symptoms that can arise while living with a diagnosis of Parkinson’s. You might wish to know why we are putting more post through your door!
The Biography of the Brain
The Devil is in the Detail! Leaping from genes to the environment, we know that certain occupations with chemical exposure and rural living carry a slightly higher risk for Parkinson’s later in life. Smoking seems to be protective (but is not recommended for many other health reasons!) and there may be further risks associated with high blood pressure, diabetes, elevated cholesterol, head injuries a history of depression or anxiety and other factors. Simple facts such as caffeine intake, fruit and vegetable consumption can all prove helpful information for the research scientist. Since Parkinson’s affects many parts of the nervous system seemingly unrelated health facts can be of great value. For example sleep disorders, smell and taste function and bowel habit (with lifelong constipation implying a higher risk) are all pieces of information that point to involvement of specific areas of the peripheral and central nervous system in Parkinson's. These ‘non-motor’ features of the illness that exist alongside tremor, slowness and stiffness are finally receiving the attention that they deserve for arriving at better treatments and promoting more wide-ranging research that will address what are often very serious and troubling symptoms. The pathologist and scientist also both need to know about complications of treatment because when these occur they may indicate changes in the brain secondary to the treatment or making the individual more vulnerable to develop complications. For example, confusion and hallucinations, dyskinesias or involuntary movements, freezing and on/off episodes may all have significance for specific brain regions and chemical activities and without detailed information the researcher cannot address these problems while studying the brain. Thus, if we lose the information about these problems during treatment we also lose the opportunity to understand them better when looking at brain tissue itself.
The Changing Story Therefore, the 100 questions will be sent out to our donors on a regular basis so that we can learn about facts as diverse as bowel and bladder function, drooling and poor speech, memory and concentration, dizzy spells related to low blood pressure, sleep and dreams and many other things including drug treatments for Parkinson's and other illnesses. With these facts describing all symptoms and side effects the Tissue Bank will be able to provide researchers with sufficient knowledge to ensure that each brain donation is made as valuable as possible. Dr Ronald Pearce, Clinical Neurologist |
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2. Research Project Report: Studies on the pathological basis of dementia and visual hallucinations in PDParkinson's disease (PD) has been characterised as a movement disorder with the main clinical features of resting tremor, bradykinesia, rigidity and abnormalities of gait, balance and posture. This underestimates the complexity of what is a multi-system disorder with many important non-motor features. Among the most prominent non-motor complications of the disease are dementia and visual hallucinations The prevalence of dementia in PD has been reported to be between 12 and 41% with PD patients having a six-fold risk for dementia over age-matched controls. Prevalence figures for visual hallucinations are in the range of 6-60%. Pathologically, PD is characterised by loss of cells in the substantia nigra pars compacta. However, it is now apparent that there is a widespread pathology in PD that greatly exceeds the classical brainstem 'locus classicus' of the substantia nigra pars compacta. Abnormal accumulation of a protein called alpha synuclein is a histopathological marker of the disease with Lewy Bodies and Lewy Neurites containing alpha synuclein. Nonetheless, other abnormally deposited proteins can also be found such as hyperphosphorylated tau and beta-amyloid that are characteristic neuropathological hallmarks of Alzheimer's disease. These abnormal proteins can be found in areas other than the substania nigra and we wanted to investigate how the location of these abnormal proteins correlate with the prevalence of dementia and hallunciations. This will help us understand how we may stave off the progress of PDD and prevent hallucinations. We designed a study selecting PD cases to isolate clinical features of interest and study the underlying anatomical and pathological basis. The medical histories of 81 cases from the UK Parkinson’s Disease Society Tissue Bank were retrospectively examined and a severity score for dementia and visual hallucinations attributed without prior knowledge of the neuropathological diagnosis. Subsequently, cases with neuropathologically and clinically confirmed PD were grouped on the basis of clinical phenotype representing the extremes of a spectrum for dementia and visual hallucinations. Hence, we investigated the type of pathology and areas in which it was present in the following groups:
Immunostaining was used to assess the extent of alpha-synuclein, tau and beta-amyloid deposition in eight brain regions affected in PD and known to subserve cognitive function. In our study we have found a clinical relevance of the abnormally deposited protein alpha-synuclein in the limbic system with respect to the occurrence of both dementia and hallucinations in PD. This system is a complex set of structures involved in emotions (e.g. fear, aggression), motivation, formation of memory and cognitive and attentional processing. In addition, it is highly interconnected with other brain structures that are also involved in cognitive functions (e.g. nucleus accumbens and prefrontal cortex). There is also evidence that the limbic system provides a custodial function for the maintenance of a healthy conscious state of mind. An improved understanding of the anatomical and pathological basis of cognitive and psychiatric symptoms in PD may ultimately contribute towards the evolution of better treatment strategies for these aspects of the illness. By studying the relationship between centres in the brain that control behaviour in Parkinson’s disease state, one will by inference add to a greater understanding of brain function in normal individuals. Mr Michail Kalaitzakis, PhD Student 3. Research Project Report: Parkinson’s disease post-mortem brain tissue for RNA quality analysis
Introduction: Human post-mortem brain tissue is one of the most valuable resources available for research into human neurological disorders. The success of experiments and reliability of data obtained from a molecular analysis of the tissue will depend on the quality of genetic material (RNA) obtained from this post-mortem tissue. RNA will be analysed using different variables to see if any of the factors affect the quality of the RNA. This will give us information on how best to obtain and store tissue i.e. with time delays etc... |
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Experiment:
This experiment was carried out to determine which of these ante and post-mortem variables affect the quality of RNA. A total of 149 snap frozen tissue samples were used in this analysis which included 70 samples from the UK MS and 32 samples from the UK PD tissue banks and 47 snap frozen tissue samples from Brain Net Europe participants. These 47 samples were provided by Barcelona (8 samples), Edinburgh (5 samples), Institutes of Psychiatry London (8 samples), Wuerzburg (8 samples), Paris (8 samples) and Munich (10 samples). RNA was extracted from all the samples using a special kit, utilising methods previously optimised for the network. RNA quantity and quality was assessed using a piece of specialised equipment, the Agilent Bioanalyser. The data obtained was analysed against predetermined variables. As the information supplied by a majority of the participants was limited to:
These were used as the main factors against which the quality of RNA was analysed. The statistical analysis of the data was carried out with advice and support from the Imperial College Statistical Advisory Service.
Results:
Future Research: Dr Francisca S Fernando Research Associate 4. Contact Information
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