NR APAA
AU Vidal,C.; Herzog,C.; Lefebvre-Roque,M.; Meric,P.; Beloeil,J.C.; Dormont,D.; Lasmezas,C.I.
TI Functional analysis of the serotoninergic system in murine models of prion diseases
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-26
PT Konferenz-Poster
AB
Although structural and molecular studies have provided much insight into prion diseases, the pathophysiological mechanisms are still largely unknown. In the CNS, the role of the neuronal phenotype, neurotransmitters and receptors in the susceptibility to infection remains to be elucidated. Several lines of evidence suggest that the serotoninergic system might be a candidate target for prion infection. The aim of the present work was to study the development of the pathophysiology in mice using non-invasive methods i.e. brain imaging (MRI, 7 tesla) and in vivo spectroscopy together with behavioural tests designed to evaluate serotoninergic functions : light/dark boxes (anxiety), hot plate test (pain), activity boxes (circadian rhythm).
Mice infected intracerebrally with a scrapie (C506M3) or ESB strain (6BP1) showed behavioral abnormalities i.e. anxiolytic-like behavior and hyperalgesia preceding clinical signs by 15/20 days. Changes in circadian activity (increased activity during the nocturnal phase) were observed concomitantly with clinical motor symptoms. Direct inoculation into the Raphe nuclei reduced the incubation period and survival time. MRI images and spectral analysis showed early signal abnormalities especially in brainstem regions.
These results suggest that the serotoninergic system may play an important role in the propagation and accumulation of the prion agents in the CNS.
Supported by GIS Prion 2002, France.
AD Catherine Vidal, Institut Pasteur, France; C. Herzog, M. Lefebvre-Roque, D. Dormont, C. Lasmézas, CEA, France; P. Méric, J.C. Beloeil, CNRS, France
SP englisch
PO Deutschland