Sexually dimorphic effects of prenatal exposure to lipopolysaccharide, and prenatal and postnatal exposure to propionic acid, on acoustic startle response and prepulse inhibition in adolescent rats: relevance to autism spectrum disorders

Kelly A Foley; Derrick F MacFabe; Martin Kavaliers; Klaus-Peter Ossenkopp

doi:10.1016/j.bbr.2014.09.032

Sexually dimorphic effects of prenatal exposure to lipopolysaccharide, and prenatal and postnatal exposure to propionic acid, on acoustic startle response and prepulse inhibition in adolescent rats: relevance to autism spectrum disorders

Behav Brain Res. 2015 Feb 1:278:244-56. doi: 10.1016/j.bbr.2014.09.032. Epub 2014 Oct 7.

Authors

Kelly A Foley¹, Derrick F MacFabe², Martin Kavaliers¹, Klaus-Peter Ossenkopp³

Affiliations

¹ Graduate Program in Neuroscience, Department of Psychology, University of Western Ontario, London, ON, Canada; The Kilee Patchell-Evans Autism Research Group, Department of Psychology, University of Western Ontario, London, ON, Canada.
² The Kilee Patchell-Evans Autism Research Group, Department of Psychology and Psychiatry, Division of Developmental Disabilities, University of Western Ontario, London, ON, Canada.
³ Graduate Program in Neuroscience, Department of Psychology, University of Western Ontario, London, ON, Canada; The Kilee Patchell-Evans Autism Research Group, Department of Psychology, University of Western Ontario, London, ON, Canada. Electronic address: ossenkop@uwo.ca.

PMID: 25300465
DOI: 10.1016/j.bbr.2014.09.032

Abstract

Potential environmental risk factors for autism spectrum disorders (ASD) include viral/bacterial infection and an altered microbiome composition. The present study investigated whether administration of immune and gastrointestinal factors during gestation and early life altered startle response and prepulse inhibition in adolescent offspring using lipopolysaccharide (LPS), a bacterial mimetic, and propionic acid (PPA), a short chain fatty acid and metabolic product of antibiotic resistant enteric bacteria. Pregnant Long-Evans rats were injected once a day with PPA (500 mg/kg SC) on G12-16, LPS (50 μg/kg SC) on G15 and G16, or vehicle control on G12-16 or G15-16. Male and female offspring were injected with PPA (500 mg/kg SC) or vehicle twice a day, every second day from postnatal days 10-18. Acoustic startle and prepulse inhibition was measured on postnatal days 45, 47, 49, and 51. Prenatal and postnatal treatments altered startle behavior in a sex-specific manner. Prenatal LPS treatment produced hyper-sensitivity to acoustic startle in males, but not females and did not alter prepulse inhibition. Subtle alterations in startle responses that disappeared with repeated trials occurred with prenatal PPA and postnatal PPA treatment in both male and female offspring. Prenatal PPA treatment decreased prepulse inhibition in females, but not males. Lastly, females receiving a double hit of PPA, prenatal and postnatal, showed sensitization to acoustic startle, providing evidence for the double hit hypothesis. The current study supports the hypotheses that immune activation and metabolic products of enteric bacteria may alter development and behavior in ways that resemble sensory abnormalities observed in ASD.

Keywords: Maternal immune activation; Neurodevelopmental disorders; Pre-pulse inhibition; Sex differences; Short chain fatty acid; Startle response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
Auditory Perception / drug effects
Child Development Disorders, Pervasive / chemically induced
Child Development Disorders, Pervasive / psychology*
Female
Lipopolysaccharides / administration & dosage
Lipopolysaccharides / pharmacology*
Male
Pregnancy
Prenatal Exposure Delayed Effects / psychology*
Prepulse Inhibition / drug effects*
Propionates / administration & dosage
Propionates / pharmacology*
Rats
Rats, Long-Evans
Reflex, Startle / drug effects*
Risk Factors
Sex Factors
Time Factors

Substances

Lipopolysaccharides
Propionates
propionic acid