Year: 2016
Type: dissertation
Study design: Observational Study
Abstract: Parkinson’s disease is characterized by selective degeneration of dopaminergic neurons in the substantia nigra, the presence of Lewy bodies and Lewy neurites containing alpha synuclein ag-gregates in such neurons, and neuroinflammation mediated by the activation of microglia and astrocytes. These pathological changes collectively contribute to the cardinal motor symptoms of Parkinson’s disease such as resting tremor, bradykinesia, rigidity, and postural instability. In ad-dition, dysfunction of non-dopaminergic neurons such as serotonergic, noradrenergic, and cho-linergic neurons, the Lewy pathology, and neuroinflammation outside of the nigro-striatal re-gions are thought to play a major role in non-motor symptoms of Parkinson’s disease such as psychiat¬ric problems, cognitive dysfunction including dementia, autonomic symptoms, and rap-id-eye movement sleep disorder. Therefore, Parkinson’s disease is a multisystem disease, affect-ing diffuse area of brain and producing various symptoms. Current trends toward use of data driven analytic methods can facilitate to expand our knowledge about Parkinson’s disease be-yond the classic basal ganglia motor model and DA dysfunction. The general aim of this thesis is to investigate a whole brain in vivo to further understand the complex neural substrates of the disease using multimodal neuroimaging tools and techniques. This thesis has shed light on the cortical and subcortical structural and functional brain changes underpinning for the clinical manifestations in Parkinson’s disease. Changes in gray and white matter as well as functional changes were evident using magnetic resonance imaging (MRI). Gray matter and functional changes occurred in the frontal cortex while white matter changes occurred more diffuse area of the brain including bilateral frontal and temporal regions and left parietal and occipital regions as well as subcortical white matter tracts. These changes were also associated with motor and cog-nitive dysfunction, suggesting that structural MRI and diffusion tensor imaging as well as resting functional MRI may be promising as in vivo biomarkers for Parkinson’s disease. Our investiga-tion of neuroinflammation using Positron Emission Tomography and an improved second gener-ation radioligand did not find any changes in the striatum of patients with Parkinson’s disease. However, demonstrated gray matter, white matter, and functional changes warrant further inves-tigations of neuroinflammation in extra-striatal and white matter regions.
Source: TSpace (University of Toronto)
Author: Yuko Koshimori
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2617522572