Showing papers on "Neurodegeneration published in 1988"
TL;DR: The data suggest the presence of a generalized defect that may affect the neurotransmitter and metabolic pool of glutamate in amyotrophic lateral sclerosis and the possibility that distribution of glutamate between the intracellular and extracellular pool may be altered in ALS and may mediate the neurodegeneration.
Abstract: Because recent studies showed a systemic defect in glutamate metabolism in amyotrophic lateral sclerosis (ALS), we measured the levels of free amino acids in frontal and cerebellar cortex and two areas of spinal cord obtained at autopsy from 22 patients who died of this disease. Glutamate levels were significantly decreased (by 21 to 40% of control values) in all areas investigated; cervical and lumbar spinal cord showed the greatest change. Aspartate levels were also significantly reduced (by 32 to 35%) in the spinal cord only. A positive correlation was shown between the changes of glutamate and aspartate as well as a significant alteration in the glutamate to glutamine ratio in the spinal cord of patients with ALS. Although we cannot exclude the possibility that these abnormalities may partly result from neuronal cell loss, the data suggest the presence of a generalized defect that may affect the neurotransmitter and metabolic pool of glutamate. The defect may be expressed more severely in the spinal cord than in other central nervous system areas. These results, taken together with the previously shown systemic abnormality, raise the possibility that distribution of glutamate between the intracellular and extracellular pool may be altered in ALS and may mediate the neurodegeneration.
217 citations
Journal Article•
TL;DR: Indirect mechanisms such as the physical or biochemical disruption of endothelial cell basement membranes or the production of toxic cytokines by virus infected cells may play a role in the development of retrovirus induced neurodegeneration.
13 citations
TL;DR: Although the neurodegeneration induced by MPTP is less widespread than that which occurs in PD, primate models based on systemic administration of this substance should be useful in assessing the efficacies of antiparkinsonism drugs and might also provide information about the etiology of PD.
Abstract: In humans, ingestion of the meperidine-analogue 1 -methyl-4-phenyl-1,2,3,6-tetrahy- dropyridine (MPTP) is known to cause parkinsonian symptoms and degeneration of the substantia nigra, effects that resemble the behavioral and pathological changes that characterize idiopathic Parkinson's disease (PD). Studies of the effects that this substance produces in animal models are reviewed and analyzed herein. Although the neurodegeneration induced by MPTP is less widespread than that which occurs in PD, primate models based on systemic administration of this substance should be useful in assessing the efficacies of antiparkinsonism drugs and might also provide information about the etiology of PD. Some limitations of the MPTP model might be overcome by using aged primates. In further defining the central mechanism of action of MPTP, it seems essential to determine which cell populations (e.g., nondopaminergic neurones, glia, vascular endothelial cells) contain the monoamine oxidase-B that catalyzes its conversion to the neurotoxic metabolite 1 -methy-4-phenylpyridiniumion. Continued study along these lines could lead to the development of effective methods for controlling PD.
10 citations