Tracing propionic acid infused to rat brain via deuterium tagging-further development of a novel rodent model of autism spectrum disorders

• Published in: Surface and interface analysis 2011-01, Vol.43 (1-2), p.358-362
• Main Authors: Nie, H.-Y., Taylor, A.R., Francis, J. T., Walzak, M. J., Lau, W. M., MacFabe, D. F.
• Format: Article
• Language: English
• Subjects: Atomic, molecular, and ion beam impact and interactions with surfaces; autism spectrum disorders; Bacteria; Brain; Condensed matter: electronic structure, electrical, magnetic, and optical properties; deuterated sodium propionate; Deuterium; Disorders; Electron and ion emission by liquids and solids; impact phenomena; Exact sciences and technology; Imaging; Impact phenomena (including electron spectra and sputtering); Infusion; ion image; neuroinflammation; oxidative stress; Physics; PPA; PPA infusion; Propionic acid; rat brain; ToF-SIMS
• ISSN: 0142-2421; 1096-9918; 1096-9918
• DOI: 10.1002/sia.3536

MacFabe et al. have proposed a novel rat model of autism spectrum disorders (ASDs) with intraventricular infusions of propionic acid (PPA), a gut bacterial metabolic end product and common food preservative, which produces reversible behavioral and electrographic effects coupled with increased oxidative stress and innate neuroinflammatory changes consistent with findings in ASD patients. PPA appears to be a potential environmental trigger linking the disparate behavioral, dietary, gut, metabolic and immune factors implicated in ASD. These previous studies used traditional immunohistochemical and biochemical techniques to examine increased oxidative stress and visualize neurons, reactive astrocytes, and activated microglia in hippocampus and adjacent external capsule white matter from coronally sectioned rat brain. As PPA is also an important metabolic intermediate of fatty acid beta oxidation, we have repeated the experiments with deuterium‐tagged PPA (DPPA) and employed ToF‐SIMS to trace the deuterium decoration of comparable brain regions ipsilateral to the DPPA infusion. In the present case of revealing DPPA‐induced changes in brain regions, ToF‐SIMS imaging of deuterium confirms the effectiveness of the methodology and the imaging results support the PPA‐triggered ASD rodent model. Copyright © 2010 John Wiley & Sons, Ltd.