Metabolic imaging of the murine brain

Abstract

Alzheimer's disease is the sixth leading cause of death in the United States. While the pathology of the disease is not fully understood, it is becoming increasingly apparent that it involves a complex homeostatic system involving multiple metals, including zinc, copper, and iron. There is also growing evidence that demonstrates developmental lead exposure may also have a role in the pathogenesis of the disease. Understanding the role of these elements in Alzheimer's disease and other metal dyshomeostasis related maladies is key in the development of treatments and possible cures. The development of metallomic imaging using systems like Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) shows great promise in tracking the distribution of individual elements in physiological tissues. However, the process is both time- and resource-consuming. In an effort to alleviate these issues, we developed a method for creating calibration standards for both LA-ICP-MS and LA-ICP-OES (Laser Ablation Inductively Coupled Plasma Optical Emission Spectrometry) and a method for creating 60µm sections for laser ablation. In addition, we also explored the capabilities and sensitivity of a LA-ICP-OES system for metallomic imaging using murine brains. While imaging of the 60µm sections will require additional calibration and fine-tuning, we were able to successfully image and identify physiological areas of interest in the murine brain by elemental distribution. Continued development of this technology will lead to better optical emission spectrometry image resolution, while freeing up the LAICP-MS for ultra-trace elemental and isotopic analysis.