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Title: 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 amore » 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.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
914383
Report Number(s):
BNL-78951-2007-JA
Journal ID: ISSN 0006-3002; BBACAQ; TRN: US200809%%214
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochim Biophys Acta; Journal Volume: 1758
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; DISEASES; LIGHT SOURCES; MOLECULAR STRUCTURE; NERVE CELLS; PROTEIN STRUCTURE; PROTEINS; GLYCOPROTEINS; national synchrotron light source

Citation Formats

Kretlow,A., Wang, Q., Kneipp, J., Lasch, P., Beekes, M., Miller, L., and Naumann, D.. FTIR-Microspectroscopy of Prion-Infected Nervous Tissue. United States: N. p., 2006. Web. doi:10.1016/j.bbamem.2006.05.026.
Kretlow,A., Wang, Q., Kneipp, J., Lasch, P., Beekes, M., Miller, L., & Naumann, D.. FTIR-Microspectroscopy of Prion-Infected Nervous Tissue. United States. doi:10.1016/j.bbamem.2006.05.026.
Kretlow,A., Wang, Q., Kneipp, J., Lasch, P., Beekes, M., Miller, L., and Naumann, D.. Sun . "FTIR-Microspectroscopy of Prion-Infected Nervous Tissue". United States. doi:10.1016/j.bbamem.2006.05.026.
@article{osti_914383,
title = {FTIR-Microspectroscopy of Prion-Infected Nervous Tissue},
author = {Kretlow,A. and Wang, Q. and Kneipp, J. and Lasch, P. and Beekes, M. and Miller, L. and Naumann, D.},
abstractNote = {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.},
doi = {10.1016/j.bbamem.2006.05.026},
journal = {Biochim Biophys Acta},
number = ,
volume = 1758,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}