FTIR-microspectroscopy of prion-infected nervous tissue

Abstract

The family of transmissible spongiform encephalopathies (TSE), also termed prion diseases, is a group of fatal, neurodegenerative diseases characterized by the accumulation of a misfolded protein, the disease-associated prion protein PrPSc. This glycoprotein differs in secondary structure from its normal, cellular isoform PrPC, which is physiologically expressed mostly by neurons. Scrapie is a prion disease first described in the 18th century in sheep and goats, and has been established as a model in rodents to study the pathogenesis and pathology of prion diseases. Assuming a multitude of molecular parameters change in the tissue in the course of the disease, FTIR microspectroscopy has been proposed as a valuable new method to study and identify prion-affected tissues due to its ability to detect a variety of changes in molecular structure and composition simultaneously. This paper reviews and discusses results from previous FTIR microspectroscopic studies on nervous tissue of scrapie-infected hamsters in the context of histological and molecular alterations known from conventional pathogenesis studies. In particular, data from studies reporting on disease-specific changes of protein structure characteristics, and also results of a recent study on hamster dorsal root ganglia (DRG) are discussed. These data include an illustration on how the application of a brilliant IR synchrotron light source enables the in situ investigation of localized changes in protein structure and composition in nervous cells or tissue due to PrPSc deposition, and a demonstration on how the IR spectral information can be correlated with results of complementary studies using immunohistochemistry and x-ray fluorescence techniques. Using IR microspectroscopy, some neurons exhibited a high accumulation of disease-associated prion protein evidenced by an increased amount of beta-sheet at narrow regions in or around the infected nervous cells. However, not all neurons from terminally diseased hamsters showed PrPSc deposition. Generally, the average spectral differences between all control and diseased DRG spectra are small but consistent as demonstrated by independent experiments. Along with studies on the purified misfolded prion protein, these data suggest that synchrotron FTIR microspectroscopy is capable of detecting the misfolded prion protein in situ without the necessity of immunostaining or purification procedures.

FTIR Imaging of Tissues: Techniques and Methods of Analysis

“…FtIR microspectroscopy studies have been focused on scrapie-infected hamsters only and they have evidenced protein changes in neurons by the observation of an IR band in the region of β-sheet conformation [142][143][144]. Worth mentioning is the fact that no relevant spectral differences in the amide I position were found in IR spectra recorded with the use of a globar source and single element detectors, but only utilizing synchrotron IR radiation revealed changes in protein conformation [144]. this was explained by the higher spatial resolution of synchrotron-based measurements that enabled detection of small-size PrP Sc deposits.…”

Biological Water Dynamics and Entropy: A Biophysical Origin of Cancer and Other Diseases

“…Infectious agents are, evidently, only taking advantage of the damage to the biological milieu wrought by EIWS. This EIWS-induced damage can include protein misfolding and/or aggregation such as that manifested in prion diseases [324,325], as well as facilitation of the membrane fusion process by which pathogenic bacteria, viruses, or even prions (pathologically misfolded proteins) invade host cells. Both of these types of pathological changes that decrease resistance to infection are considered in more detail below.…”

Disease recognition by infrared and Raman spectroscopy

“…FTIR microspectroscopy of prion diseases has been recently reviewed [65,66]. This method was proposed to identify prion-affected nervous cells or tissues due to its ability to detect localized changes in structure and composition of disease-associated prion protein PrP sc .…”