Our long-term goal is to understand the specific changes in brain of patients with dominantly a inherited olivopontocerebellar atrophy [OPCA) responsible for the neurobehavioural disturbances and the etiology of this condition. This will be achieved through an intensive multidisciplinary approach involving annual neurological and neuropsychological assessment of 30 U.s. OPCA patients and, at autopsy follow-up, postmortem brain neurochemical and neuropathological analyses.
Our specific aims are to: 1) define the role of brain cholinergic system dysfunction in the cognitive deficits of OPCA; 2) determine the biochemical factors which might cause OPCA through examination in postmortem brain of phospholipid and energy metabolic processes, and programmed cell death mechanisms; 3) establish OPCA as a model of early nigrostriatal dopamine neurone degeneration and 4) improve the life of the OPCA patient through dvsohaaia intervention. We expect that these studies will identify processes involved in the brain degeneration of OPCA as well as the brain structures responsible for the cognitive impairment of this disorder which, in some patients, is an important clinical management issue. The obtained results are also likely to be relevant to brain pathophysiological processes in other spino cerebellar ataxia disorders and in more common human brain conditions [Alzheimer's disease, Parkinson's disease, normal aging) which share with OPCA certain biochemical features.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS026034-08
Application #
2265775
Study Section
Neurology A Study Section (NEUA)
Project Start
1988-06-01
Project End
1997-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
8
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Centre for Addiction and Mental Health
Department
Type
DUNS #
City
Toronto
State
ON
Country
Canada
Zip Code
M5S2S-1
Haycock, John W; Becker, Laurence; Ang, Lee et al. (2003) Marked disparity between age-related changes in dopamine and other presynaptic dopaminergic markers in human striatum. J Neurochem 87:574-85
Morrison, L D; Cao, X C; Kish, S J (1998) Ornithine decarboxylase in human brain: influence of aging, regional distribution, and Alzheimer's disease. J Neurochem 71:288-94
Montermini, L; Kish, S J; Jiralerspong, S et al. (1997) Somatic mosaicism for Friedreich's ataxia GAA triplet repeat expansions in the central nervous system. Neurology 49:606-10
Mastrogiacoma, F; Lindsay, J G; Bettendorff, L et al. (1996) Brain protein and alpha-ketoglutarate dehydrogenase complex activity in Alzheimer's disease. Ann Neurol 39:592-8
Bettendorff, L; Mastrogiacomo, F; LaMarche, J et al. (1996) Brain levels of thiamine and its phosphate esters in Friedreich's ataxia and spinocerebellar ataxia type 1. Mov Disord 11:437-9
Morrison, L D; Smith, D D; Kish, S J (1996) Brain S-adenosylmethionine levels are severely decreased in Alzheimer's disease. J Neurochem 67:1328-31
Mastrogiacomo, F; LaMarche, J; Dozic, S et al. (1996) Immunoreactive levels of alpha-ketoglutarate dehydrogenase subunits in Friedreich's ataxia and spinocerebellar ataxia type 1. Neurodegeneration 5:27-33
Mastrogiacoma, F; Bettendorff, L; Grisar, T et al. (1996) Brain thiamine, its phosphate esters, and its metabolizing enzymes in Alzheimer's disease. Ann Neurol 39:585-91
Ross, B M; Kim, D K; Bonventre, J V et al. (1995) Characterization of a novel phospholipase A2 activity in human brain. J Neurochem 64:2213-21
Kish, S J; Zhong, X H; Hornykiewicz, O et al. (1995) Striatal 3,4-dihydroxyphenylalanine decarboxylase in aging: disparity between postmortem and positron emission tomography studies? Ann Neurol 38:260-4

Showing the most recent 10 out of 31 publications