The neurodegeneration sequence in prion diseases: evidence from functional, morphological and ultrastructural studies of the GABAergic system

Journal of Neuropathology and Experimental Neurology
Essia Bouzamondo-BernsteinStephen J DeArmond

Abstract

Loss of the GABAergic system of neurons has been reported to be the first detectable neuropathological change in prion diseases, which features the accumulation of an aberrant isoform of the prion protein (PrP(Sc)). To determine the timing of GABAergic system dysfunction and degeneration and its relationship to PrP(Sc) accumulation during the course of prion disease in Syrian hamsters, we applied 3 approaches: i) quantifying GABA-immunopositive neurons and their processes by light and electron microscopy to test for selective loss; ii) measuring evoked [3H]-GABA release from synaptosomes to test for functional abnormalities; and iii) determining the kinetics of PrP(Sc) accumulation in subcellular fractions to correlate it with GABAergic dysfunction. At the terminal stages of disease, we found a significant increase in the number of GABA-positive and -negative presynaptic boutons with abnormally aggregated synaptic vesicles. At the same stage, we also found an equal degree of GABA-immunopositive and -immunonegative presynaptic bouton loss. In contrast, GABA-positive neocortical cell bodies increased, based on stereologic estimates in the terminal stage of scrapie. In the context of these abnormalities, evoked release of [3H]-GAB...Continue Reading

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Citations

Sep 3, 2017·Journal of Neuropathology and Experimental Neurology·Stephen J DeArmond
Dec 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Roberto ChiesaDavid A Harris
Mar 3, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jiri G SafarStanley B Prusiner
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Mar 29, 2008·Acta Neuropathologica·Jean-Guy FournierJean-Philippe Deslys
Jan 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Nako IshikuraStephen J DeArmond
Jul 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Patricia SpilmanStephen J Dearmond
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