NR AEYA
AU Guentchev,M.; Groschup,M.H.; Kordek,R.; Liberski,P.P.; Budka,H.
TI Severe, early and selective loss of a subpopulation of GABAergic inhibitory neurons in experimental transmissible spongiform encephalopathies
QU Brain Pathology 1998 Oct; 8(4): 615-23
PT journal article
AB Little is known about the pathogenetic basis of characteristic symptoms in transmissible spongiform encephalopathies (TSEs) such as myoclonus and characteristic EEG hyperactivity. We investigated the GABAergic system and its subpopulations in mice inoculated with experimental scrapie (ME7, RML, 22A strains) and Creutzfeldt-Jakob disease (CJD; Fujisaki strain), to study damage to inhibitory neurons. Since recent studies have shown electrophysiological changes in prion protein (PrP) knockout mice, we also studied mice lacking or overexpressing the PrP gene. Antibodies against glutamic acid decarboxylase (GAD), parvalbumin (PV), calbindin (CB), and calretinin (CR) were used to stain GABAergic neurons, and isolectin-B4 to stain perineuronal nets around PV+ neurons. In scrapie infected mice, cortical PV+ neurons were severely reduced while CB+ and CR+ neurons were well preserved. In CJD inoculated mice, loss of PV+ neurons was severe and occurred very early after inoculation. PrP-/- and tg20 mice showed normal appearance of PV, CB, CR, GAD+ neurons and their neuropil, and of isolectin-B4+ perineuronal nets. The early, severe and selective loss of cortical PV+ neurons in experimental scrapie and CJD suggest selective loss of PV+ GABAergic neurons as important event during disease development, possibly as one basis of excitatory symptoms in TSEs.
IN Das Prionprotein nicht, normal, oder übermäßig exprimierende Mäuse wurden mit den Scrapie-Stämmen ME7, RML und 22A bzw. dem Fujisaki-Creutzfeldt-Jakob-Erreger infiziert. Bei das Prionprotein normal exprimierenden Mäusen wurden spezifisch die inhibierenden, GABAergen, cortikalen Neuronen reduziert, welche Parvalbumin exprimieren. Die Zahl der ebenfalls GABAergen, jedoch Calbindin oder Calretin exprimierenden Neuronen blieb dagegen unverändert. Bei den das Prionprotein nicht oder übermäßig exprimierenden Mäusen blieb die Expression von Paralbumin, Calbindin, Calretin, Glutamatdecarboxylase in Neuronen, sowie die Isolectin-B-Expression perineuronaler Zellen konstant.
ZR 37
MH Animal; Brain/pathology; Brain Chemistry; Disease Progression; Histocytochemistry; Mice; Mice, Inbred C57BL; Neurons/*pathology/physiology; Prion Diseases/metabolism/*pathology; Prions/metabolism; Scrapie/pathology; Support, Non-U.S. Gov't; gamma-Aminobutyric Acid/*physiology
AD Austrian Reference Center for Human Prion Diseases and Institute of Neurology, University of Vienna.
SP englisch
PO Schweiz