A marked disparity between the expression of prion protein and its message by neurones of the CNS

Expression of the normal cellular form of prion protein is both necessary and rate-limiting in the spread of prion disease, yet its cellular expression in vivo is poorly understood. To optimise immunohistochemical labelling of this protein in mouse brain, we have developed novel antibodies that recognise cellular prion protein in glutaraldehyde-fixed tissue. Expression was found to be predominantly neuronal. and to differ between different classes of neurone. Thus, neurones immunoreactive for GABA expressed very high levels of normal prion protein most projection neurones expressed much lower levels, particularly on their axons in the major fibre tracts, and some neurones (e.g. those positive for dopamine) displayed no detectable prion protein. In marked contrast, all neurones, even those that were immuno-negative, expressed high levels of message for prion protein. shown by non-radioactive in situ hybridisation. Glia expressed very low levels of message, and undetectable levels of prion protein, We conclude that the steady-state level of prion protein. which differs so markedly between different neuronal types, is primarily controlled post-transcriptionally possible by differences in protein trafficking or degradation. These marked differences in the way different neurones produce and/or degrade their normal cellular prion protein may influence the selective spread and neurotoxic targeting of prion diseases within the CNS. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.