Maternal Immune Activation during Pregnancy Induces Gender-Specific Behavioral Effects in Offspring

Background:  Autism spectrum disorders are neurodevelopmental disorders that are characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors.  Epidemiological and biochemical evidence suggests that a subpopulation of autism may be linked to immune perturbations that occur during fetal development.  These findings have given rise to the maternal immune activation (MIA) model of neurodevelopmental disorders in which the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied.  

Objectives:  The objectives were to (a) compare the induction of MIA using lipopolysaccharide (LPS) with that of polyinosinic:polycytidylic acid (Poly IC) in terms of behavioral effects on offspring, and (b) to examine gender effects of these treatments.

Methods:  C57BL/6 mouse dams were treated with either LPS or Poly IC during mid-gestation to mimic a bacterial or viral infection respectively.  Autism-associated behaviors were assessed in the adult offspring using motor activity tests to evaluate locomotion and exploration in a novel environment, two versions of the three-chamber testing paradigm to test sociability, and the marble burying test and self-grooming analyses to investigate repetitive behavior.  

Results:  We found that prenatal LPS treatment caused female-specific increases in thigmotaxis behavior as well as modest decreases in sociability and self-grooming during habituation.   In contrast, Poly IC treatment caused a male-specific reduction in motor activity concomitant with increased repetitive behaviors.  

Conclusions:  We conclude that autism-related behaviors observed in the mouse model of maternal immune activation are dependent on the type of immune stimulus given to the mother, and the gender of the offspring.