Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism.
Propionic acid (PPA) is a dietary short chain fatty acid and a metabolic end-product of enteric bacteria. Intracerebroventricular (ICV) injections of PPA can result in brain and behavioral abnormalities in rats similar to those seen in humans suffering from autism. To evaluate cognition and sensorimotor ability in the PPA model, male Long-Evans hooded rats received ICV injection of PPA or control compounds prior to behavioral testing in water maze and beam tasks. Compared to controls, PPA-treated rats were impaired in the water maze task as indicated by an unusual pattern of mild or no impairment during spatial acquisition training, but marked impairment during spatial reversal training. PPA-treated rats were also impaired on the beam task. Neuropathological analysis from PPA-treated rats revealed an innate neuroinflammatory response. These findings add to evidence that PPA can change the brain and behavior in the laboratory rat consistent with symptoms of human autism.
Shultz
Sandy R
SR
The Kilee Patchell-Evans Autism Research Group, Department of Psychology and Graduate Program in Neuroscience, University of Western Ontario, London, Canada. sshultz@uwo.ca
Macfabe
Derrick F
DF
Martin
Samantha
S
Jackson
Jordana
J
Taylor
Roy
R
Boon
Francis
F
Ossenkopp
Klaus-Peter
KP
Cain
Donald P
DP
D000433:1-Propanol / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced*; D004195:Disease Models, Animal; D020233:Gait Disorders, Neurologic / Q000139:chemically induced*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008840:Microfilament Proteins; D011422:Propionates / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects; D013550:Swimming; D000097382:CD68 Molecule
D000433:1-Propanol; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D011422:Propionates; C100745:Aif1 protein, rat; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C029658:propionic acid