Rezaie, P.; Male, D. K.; Collinge, J. and Lantos, P. L.
|DOI (Digital Object Identifier) Link:||http://dx.doi.org/10.1046/j.0305-1846.2000.02000.x|
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Introduction: The group of infectious neurodegenerative disorders collectively termed prion diseases or `transmissible spongiform encephalopathies' [TSEs] are widely regarded as lacking an overt inflammatory response within the CNS. However, recent evidence from animal models, culture studies and experiments in vivo demonstrate that TSEs induce `unconventional' immune reactions within the CNS [Betmouni et al. Neuropath Appl Neurobiol 1999; 25 : 20, Peyrin et al. Neuroreport 1999; 10 : 723]. Expression of chemotactic cytokines (chemokines) is recognized as necessary for specific recruitment of leukocyte subsets and microglia to inflammatory foci within the CNS. The aim of this investigation was to determine whether chemokines play a role in the pathogenesis of CJD. Materials and Methods: Human cases diagnosed with CJD (15 sporadic, 5 familial and 3 new variant) and transgenic Tg152 mice (Hu PrP+/+Prnp o/o) intracerebrally inoculated with CJD homogenates were screened for expression of prion protein (PrP), microglial markers (PGM-1, F4/80, Iba-1), astrocytes (GFAP), MHC class II, apoptotic markers (p53, caspase-3, AnnexinV, TUNEL), and chemokines MCP-1, RANTES, IP-10 and Fractalkine. Results: The chemokines Fractalkine (neurons), IP-10 (blood vessels) and MCP-1 (blood vessels and neurons) display inoculum-specific upregulation that precedes PrP deposition, microglial activation and detection of markers associated with apoptosis in the transgenic model of CJD, up to 2 months postinoculation. In contrast human cases of CJD show minimal reactivity within the CNS at postmortem. Conclusion: We propose that neuronal and vascular expression of chemokines provide early signals for a localized `neuro-immune' response and the recruitment of microglia in CJD.
|Item Type:||Conference Item|
|Extra Information:||Conference programme and abstracts published in Neuropathology and Applied Neurobiology 27 (2)|
|Academic Unit/Department:||Science > Life, Health and Chemical Sciences
|Interdisciplinary Research Centre:||Biomedical Research Network (BRN)|
|Depositing User:||Payam Rezaie|
|Date Deposited:||17 Oct 2007|
|Last Modified:||14 Jan 2016 16:47|
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