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

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 behavioural 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 behavioural, 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.