Changes in HSP gene and protein expression in natural scrapie with brain damage

Carmen Serrano,Jorge H Calvo,Ane Marcos-Carcavilla,Cristina Acín,Luis Varona,Jaber Lyahyai,Inmaculada Martín-Burriel,Rosa Bolea,Hicham Filali,Juan J Badiola,Magdalena Serrano,Pilar Zaragoza

doi:10.1186/1297-9716-42-13

Abstract

Heat shock proteins (Hsp) perform cytoprotective functions such as apoptosis regulation and inflammatory response control. These proteins can also be secreted to the extracellular medium, acting as inflammatory mediators, and their chaperone activity permits correct folding of proteins and avoids the aggregation of anomalous isoforms. Several studies have proposed the implication of Hsp in prion diseases. We analysed the gene expression and protein distribution of different members of the Hsp27, Hsp70, and Hsp90 families in the central nervous system of sheep naturally infected with scrapie. Different expression profiles were observed in the areas analysed. Whereas changes in transcript levels were not observed in the cerebellum or medulla oblongata, a significant decrease in HSP27 and HSP90 was detected in the prefrontal cortex. In contrast, HSP73 was over-expressed in diencephalons of scrapie animals. Western blotting did not reveal significant differences in Hsp90 and Hsp70 protein expression between scrapie and control animals. Expression rates identified by real-time RT-PCR and western blotting were compared with the extent of classical scrapie lesions using stepwise regression. Changes in Hsp gene and protein expression were associated with prion protein deposition, gliosis and spongiosis rather than with apoptosis. Finally, immunohistochemistry revealed intense Hsp70 and Hsp90 immunolabelling in Purkinje cells of scrapie sheep. In contrast, controls displayed little or no staining in these cells. The observed differences in gene expression and protein distribution suggest that the heat shock proteins analysed play a role in the natural form of the disease.

Highlights

Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy in cattle, and several human neuropathies such as Creutzfeldt-Jakob disease or fatal familial insomnia
We present here the first gene expression analysis of four members of the HSP27 (HSPB1), HSP70, and HSP90 gene families, their protein expression profiles, and their distribution in the central nervous systems of sheep naturally infected with clinical-stage scrapie
The expression of the four HSP genes was analysed in four different areas of the central nervous system of scrapie-infected and control sheep

Summary

Introduction

Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy in cattle, and several human neuropathies such as Creutzfeldt-Jakob disease or fatal familial insomnia. These diseases are characterised by the accumulation in the central nervous system of an abnormally folded version (PrPSc) of a normal cellular protein, PrPC. Various mechanisms have been proposed to explain neuronal death in prion diseases, apoptosis and autophagy are the types of cell death considered most likely to be involved [6]. Other factors could be involved in the regulation of cell death in natural scrapie

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