Impaired Spatial Cognition in Adult Rats Treated with Multiple Intracerebroventricular (ICV) Infusions of the Enteric Bacterial Metabolite, Propionic Acid, and Return to Baseline After 1Week of No Treatment: Contribution to a Rodent Model of ASD.

Abstract

Propionic acid (PPA) is a dietary short chain fatty acid and an enteric bacterial metabolite. Intracerebroventricular (ICV) infusions of PPA in rodents have been shown to produce behavioral changes similar to those seen in autism spectrum disorders (ASD), including perseveration. The effects of ICV infusions of PPA on spatial cognition were examined by giving rats infusions of either PPA (0.26M, pH 7.4, 4μl/infusion) or phosphate-buffered saline (PBS, 0.1M) twice a day for 7days. The rats were then tested in the Morris water maze (MWM) for acquisition of spatial learning. After a recovery period of 1week of no treatment, the rats were then tested for reversal of spatial learning in the MWM. PPA-treated rats showed impaired spatial learning in the maze, relative to controls, as demonstrated by increased search latencies, fewer direct and circle swims, and more time spent in the periphery of the maze than PBS controls. After a recovery period of 1week of no treatment, these animals exhibited normal spatial reversal learning indicating that the behavioral cognitive deficits caused by PPA seem to be reversible.