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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

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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 (0.26 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.

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Acknowledgments

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

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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Authors and Affiliations

  1. Graduate Program in Neuroscience, Western University, London, Ontario, Canada

    Jennifer R. Mepham, Kelly A. Foley, Donald P. Cain & Klaus-Peter Ossenkopp

  2. The Kilee Patchell-Evans Autism Research Group, Department of Psychology, Western University, London, Ontario, Canada

    Jennifer R. Mepham, Francis H. Boon, Kelly A. Foley, Donald P. Cain, Derrick F. MacFabe & Klaus-Peter Ossenkopp

  3. Department of Psychology, Western University, London, Ontario, N6A 5C2, Canada

    Francis H. Boon, Donald P. Cain, Derrick F. MacFabe & Klaus-Peter Ossenkopp

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  1. Jennifer R. Mepham
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  2. Francis H. Boon
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Correspondence to Klaus-Peter Ossenkopp.

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Mepham, J.R., Boon, F.H., Foley, K.A. et al. 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. Neurotox Res 35, 823–837 (2019). https://doi.org/10.1007/s12640-019-0002-z

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