Effects of maternal immune activation with lipopolysaccharide on adult offspring behaviors and immune regulation

Researcher(s)

  • Baze Gianiodis, Neuroscience, University of Delaware

Faculty Mentor(s)

  • Jaclyn Schwarz, Psychological and Brain Sciences, University of Delaware

Abstract

Epidemiological studies suggest that there is an increased risk of experiencing symptoms of neurodevelopmental disorders – including ADHD, schizophrenia, autism spectrum disorder, and general learning disabilities – if one’s mother had some type of infection during gestation.

 

Lipopolysaccharide (LPS) results in maternal immune activation (MIA), which affects the expression of various cytokines and effector cells in the fetus, the rat dams, and even those offspring after they are born. MIA has also resulted in adverse behavioral outcomes in adult offspring – such as deficits in latent inhibition and novel object learning.

 

Pregnant Sprague-Dawley rat dams were injected with LPS (50ug/ml/kg, i.p.) or saline on embryonic day (E)15. After birth, the offspring were weaned and left undisturbed until adulthood. On postnatal day (P)90 to P93, male and female offspring were tested in a latent inhibition of auditory fear conditioning task. The other half of the offspring were tested in a novel object location and recognition task from P91 to P92. Following behavioral testing, to examine how MIA influences the immune response in adulthood, offspring were injected with LPS (50ug/ml/kg, i.p.) or saline and euthanized 4 hours later. Half brains were dissected to collect brain regions of interest, such as the amygdala. Polymerase-chain reaction (PCR) was then performed to examine the expression of cytokines and neurotrophic factors following the immune challenge.

 

The goal of this project is to expound upon how MIA, caused by LPS, impacts brain and behavioral processes in adult offspring. More specifically, we seek to determine the

effects of MIA by examining the adult neuroimmune response and potential learning deficits in auditory fear conditioning and novel object tasks.

 

These findings will provide us with a better understanding of  how early-life environmental factors, like MIA, affect later-in-life brain and behavioral processes in adult offspring that are associated with neurodevelopmental disorders.