Brain microglia were activated in sporadic CJD but almost unchanged in fatal familial insomnia and G114V genetic CJD

Qi Shi,Wu-Ling Xie,Cao Chen,Ke Ren,Jin Zhang,Xiao-Mei Zhang,Xiao-Ping Dong,Yin Xu,Baoyun Zhang,Li-Na Chen,Ke Wang

doi:10.1186/1743-422x-10-216

Abstract

BackgroundMicroglial activations have been described in different subtypes of human prion diseases such as sporadic Creutzfeldt-Jakob disease (CJD), variant CJD, Kuru and Gerstmann-Sträussler-Scheinker disease (GSS). However, the situation of microglia in other genetic prion diseases such as fatal familial insomnia (FFI) and familial CJD remains less understood. The brain microglia was evaluated comparatively between the FFI, G114V and sCJD cases in the study.MethodsSpecific Western blots, immunohistochemical and immunofluorescent assays were used to detect the changes of microglia and ELISA tests were used for levels of inflammatory cytokines.ResultsWestern blots, immunohistochemical and immunofluorescent assays illustrated almost unchanged microglia in the temporal lobes of FFI and G114V gCJD, but obviously increased in those of sCJD. The Iba1-levels maintained comparable in six different brain regions of FFI and G114V cases, including thalamus, cingulate gyrus, frontal cortex, parietal cortex, occipital cortex and temporal cortex. ELISA tests for inflammatory cytokines revealed significantly up-regulated IL-1β, IL-6 and TNF-α in the brain homogenates from sCJD, but not in those from FFI and G114V gCJD.ConclusionData here demonstrates silent brain microglia in FFI and G114V gCJD but obviously increased in sCJD, which reflects various pathogenesis of different human prion diseases subtypes.

Highlights

Human prion diseases or human transmissible encephalopathies (TSEs) are fatal neurodegenerative disorders including Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Str äussler-Scheinker disease (GSS) and fatal familial insomnia (FFI)
The temporal lobes of seven human prion diseases were enrolled into the assays for PrPSc, among them, one was biopsy specimen and the rest were postmortem ones
The levels of several cytokines, including IL-1β, IL-6 and TNF-α, in the brains of sporadic CJD (sCJD) show significantly increased, possibly reflecting an activated situation of microglia, while those in the brains of FFI cases and G114V genetic CJD (gCJD) case maintain comparable as normal control

Summary

Introduction

Human prion diseases or human transmissible encephalopathies (TSEs) are fatal neurodegenerative disorders including Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Str äussler-Scheinker disease (GSS) and fatal familial insomnia (FFI). They can be sporadic, e.g. sporadic CJD (sCJD), inherited, e.g. genetic CJD (gCJD), GSS and FFI, or acquired by infection, e.g. Kuru, iatrogenic CJD (iCJD). Microglial cells possess an extremely plastic chameleon-like phenotype, which respond sensitively to pathological challenges [2]. Upon activation, they transform into phagocytes and release a range of substances, such as cytokines/chemokines, nitric oxide, free radicals and neurotrophic molecules. The brain microglia was evaluated comparatively between the FFI, G114V and sCJD cases in the study

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Conclusion