GBMSDG Meeting Archives
June 11, 2009
Dr. Sabine Becker
Research Center Juelich
Bio-Imaging of Metals in Thin Tissue Sections
of Brain by Laser Ablation Inductively Coupled Plasma
Mass Spectrometry (LA-ICP-MS) Combined to Metallomics:
The New Challenge for Neuroscience
Boston University Medical School
In recent years, there has been a growing interest in studying elemental distribution in biological and especially in clinical tissues. Metal ions such as Cu, Zn, Fe, Mn, K, Na, Ca, Mg and others required for cell development, differentiation, function and survival play an important role in all biological processes. It is known that an excess of essential metals such as Fe, Cu, and Zn in the brain results in significant neurological diseases. In most neurodegenerative diseases, abnormal metal deposition has been observed within the brain [e.g. in Alzheimer's, Parkinson's or Wilson's diseases]. The quantitative imaging of metals is of increasing importance for a better understanding of the disease mechanisms underlying neurodegenerative disorders.
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) using double-focusing sector field and quadrupole-based mass spectrometers was developed to produce quantitative images of the detailed regionally specific metal distribution in 10- to 40-µm thin sections of different parts of human and rodent brain tissues. Thin biological tissue sections of brain were analyzed together with the synthetic laboratory standards under the same experimental conditions by LA-ICP-MS. This elemental analytical technique enables images to be produced of the distribution of essential metals, non-metals (like P, C, Cl or S) as well as toxic metals (e.g. Pb or U) in thin brain tissue sections with a spatial resolution in the µm range.
LA-ICP-MS images of metals and also of non-metals were obtained on thin sections of human, mouse and rat brain tissues to study, for example, aging, cancer growth, stroke, Alzheimer's or Parkinson's disease. Parkinson's disease is one of the most common disorders of the nervous system caused by loss of nerve cells (dopaminergic neurons) in the substantia nigra. Abnormal metal deposition has been observed within specific areas of the Parkinson mouse brain by LA-ICP-MS imaging compared to control samples.
In addition, LA-ICP-MS was applied to analyze metalloproteins in protein bands or spots separated by one- and two-dimensional gel electrophoresis. Metal imaging and metallomics in brain represent new analytical ways to study the disease mechanisms underlying neurodegenerative disorders.
In future studies, the possibility of nanometer scale analysis of elements on sample surfaces using near-field LA-ICP-MS (NF-LA-ICP-MS) will open up a challenging new path for future applications in the life sciences, biology and medicine.
Becker J.S., Inorganic Mass Spectrometry: Principles and Application; J. Wiley and Sons: Chichester, 2007.
Becker J.S. et al., Bioimaging of Metals by LA-ICP-MS, Mass Spectrom. Rev., published on-line, 2009.
Becker, J.S. Jakubowski, N. The Synergy of Elemental and Biomolecular Mass Spectrometry: New Analytical Strategies in Life Sciences, Chem. Soc. Rev., 2009, published on-line , DOI: 10.1039/B618635C.
Becker, J.S. et al., Anal. Chem., 2005, 77, 3208-3216; 77 (2005) 5851-5860; 79 (2007) 6074-6080.
Becker, J.S. et al. J. Anal. At. Spectrom. 19 (2004) 149; 20 (2005) 912; 22 (2007) 736; 23 (2008) 1275.
Dr. Becker with guest
Dr. Becker introduction
Presenters and sponsors