Category Archives: Lewy Bodies

Oxidative stress as a cause of nigral cell death in Parkinson’s disease and incidental lewy body disease

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The Lewy Bodies they describe below are due to oxidative stress. This can be improved. Generally due to low Glutathione levels there is damage that occurs in the SN. Glutathione is the bodies main anti-oxidant. See GlutaGenic.com for more on this and consider signing up for the free 7 secrets to raising glutathione.

 

Abstract

We examine the evidence for free radical involvement and oxidative stress in the pathological process underlying Parkinson’s disease, from postmortem brain tissue. The concept of free radical involvement is supported by enhanced basal lipid peroxidation in substantia nigra in patients with Parkinson’s disease, demonstrated by increased levels of malondialdehyde and lipid hydroperoxides. The activity of many of the protective mechanisms against oxidative stress does not seem to be significantly altered in the nigra in Parkinson’s disease. Thus, activities of catalase and glutathione peroxidase are more or less unchanged, as are concentrations of vitamin C and vitamin E. The activity of mitochondrial superoxide dismutase and the levels of the antioxidant ion zinc are, however, increased, which may reflect oxidative stress in substantia nigra. Levels of reduced glutathione are decreased in nigra in Parkinson’s disease; this decrease does not occur in other brain areas or in other neurodegenerative illnesses affecting this brain region (i.e., multiple system atrophy, progressive supranuclear palsy). Altered glutathione metabolism may prevent inactivation of hydrogen peroxide and enhance formation of toxic hydroxyl radicals. In brain material from patients with incidental Lewy body disease (presymptomatic Parkinson’s disease), there is no evidence for alterations in iron metabolism and no significant change in mitochondrial complex I function. The levels of reduced glutathione in substantia nigra, however, are reduced to the same extent as in advanced Parkinson’s disease. These data suggest that changes in glutathione function are an early component of the pathological process of Parkinson’s disease. The data presented suggest (1) there is oxidative stress in the substantia nigra at the time of death in advanced Parkinson’s disease that manifests in terms of increased lipid peroxidation, superoxide dismutase activity, and zinc levels; (2) there is a major impairment of the glutathione pathway in Parkinson’s disease; and (3) alterations in reduced glutathione levels may occur very early in the illness.

AGEING AND PARKINSON’S DISEASE: SUBSTANTIA NIGRA REGIONAL SELECTIVITY

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The following article is a bit technical. The Lewy Bodies they describe below are due to oxidative stress. This can be improved as the main culprits is poor circulation which is improved with better cranial function. SeeFunctionalCranialRelease.com for more on this. The other issue is generally due to Glutathione levels. Glutathione is the bodies main anti-oxidant. SeeGlutaGenic.com for more on this and consider signing up for the free 7 secrets to raising glutathione.

The micro-architecture of the substantia nigra was studied in control cases of varying age and patients with parkinsonism. A single 7μ section stained with haematoxylin and eosin was examined at a specific level within the caudal nigra using strict criteria. The pars compacta was divided into a ventral and a dorsaltier, and each tier was further subdivided into 3 regions. In 36 control cases there was a linear fallout of pigmented neurons with advancing age in the pars compacta of the caudal substantia nigra at a rate of 4.7% per decade. Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%). In 20 Parkinson’s disease (PD) cases of varying disease duration there was an exponential loss of pigmented neurons with a 45% loss in the first decade. Regionally, the pattern was opposite to ageing. Loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and the dorsal tier (56%). The presymptomatic phase of PD from the onset of neuronal loss was estimated to be about 5 yrs. This phase is represented by incidental Lewy body cases: individuals who die without clinical signs of PD or dementia, but who are found to have Lewy bodies at post-mortem. In 7 cases cell loss was confined to the lateral ventral tier (average loss 52%) congruent with the lateral ventral selectivity of symptomatic PD. It was calculated that at the onset of symptoms there was a 68% cell loss in the lateral ventral tier and a 48% loss in the caudal nigra as a whole. The regional selectivity of PD is relatively specific. In 15 cases of striatonigral degeneration the distribution of cell loss was similar, but the loss in the dorsal tier was greater than PD by 21%. In 14 cases of Steele-Richardson- Olszewski syndrome (SRO) there was no predilection for the lateral ventral tier, but a tendency to involve the medial nigra and spare the lateral. These findings suggest that agerelated of pigmented nigral cells is not an important factor in the pathogenesis of PD.