Neurotoxicity Research

, Volume 35, Issue 4, pp 823–837 | Cite as

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

  • Jennifer R. Mepham
  • Francis H. Boon
  • Kelly A. Foley
  • Donald P. Cain
  • Derrick F. MacFabe
  • Klaus-Peter OssenkoppEmail author
Original Article


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 (0.26 M, pH 7.4, 4 μl/infusion) or phosphate-buffered saline (PBS, 0.1 M) twice a day for 7 days. The rats were then tested in the Morris water maze (MWM) for acquisition of spatial learning. After a recovery period of 1 week 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 1 week of no treatment, these animals exhibited normal spatial reversal learning indicating that the behavioral cognitive deficits caused by PPA seem to be reversible.


Autism spectrum disorders Animal model Spatial cognition Perseveration Short chain fatty acid Rat 



We would also like to express our utmost thanks to David Patchell-Evans, for his tireless devotion to persons with autism, and his daughter, Kilee Patchell-Evans.

Funding Information

This research was supported by contributions from the GoodLife Children’s Charities and Autism Research Institute to Derrick MacFabe. It was also supported by the Natural Sciences and Engineering Research Council of Canada Discovery Grants, and Research Tools and Instruments Grants, awarded to Klaus-Peter Ossenkopp and Donald P. Cain. Jennifer Mepham was supported by an Ontario Graduate Scholarship.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Graduate Program in NeuroscienceWestern UniversityLondonCanada
  2. 2.The Kilee Patchell-Evans Autism Research Group, Department of PsychologyWestern UniversityLondonCanada
  3. 3.Department of PsychologyWestern UniversityLondonCanada

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