The Impact of Formic Acid Treatment on Brain Tissues for Prion Inactivation

There are significant risks in clinical, diagnostic, and research settings to those who investigate prion diseases, due to the difficult nature of inactivating prion proteins with standard decontamination methods. Formic acid treatment has been shown to be effective for decontaminating infectious prions and commonly used in biosafety practice to prevent occupational exposure. However, the impact of formic acid protocols on the morphology of tissue samples has not been adequately documented. The goal of this study is to examine morphologic effects of formic acid treatment on central nervous system tissue, using mouse model brain hemisphere tissues that exhibit varying degrees of neurodegeneration as a model. This study included normal, non-diseased wild-type tissues and a 5xFAD model, which recapitulates aspects of Alzheimer's Disease (AD). A model exhibiting Chronic Wasting Disease (CWD), a prion disease of deer and elk, was also used to analyze the effects of formic acid on tissues with spongiform changes. Tissues from both formic acid and untreated control treatment groups were embedded in paraffin, sectioned, stained, and imaged microscopically. Anatomical regions were analyzed and evaluated quantitatively to determine the width, area, and structural integrity of the tissue between treatment groups. Our findings demonstrated that while formic acid has been previously reported to effectively inactivate prions, it compromised the morphology of mouse brain tissues. Furthermore, the effects of formic acid were not distributed equally between regions of the brain. Age did not play a role in the morphologic changes seen in the formic acid treatment group. Interestingly, the presence of neurodegeneration in the tissues did not appear to exacerbate the effects of morphological changes post-formic acid treatment. These results emphasize the need to explore alternative prion inactivation methods that ensure the safety and reliability of handling prion-infected tissues without compromising the integrity of tissues.