Maternal Immune Activation Alters Adult Behavior, Gut Microbiome and Juvenile Brain Oscillations in Ferrets

Abstract

Maternal immune activation (MIA) has been identified as a causal factor in psychiatric disorders by epidemiological studies in humans and mechanistic studies in rodent models. Addressing this gap in species between mice and human will accelerate the understanding of the role of MIA in the etiology of psychiatric disorders. Here, we provide the first study of MIA in the ferret ( Mustela putorius furo), an animal model with a rich history of developmental investigations due to the similarities in developmental programs and cortical organization with primates. We found that after MIA by injection of PolyIC in the pregnant mother animal, the adult offspring exhibited reduced social behavior, less eye contact with humans, decreased recognition memory, a sex-specific increase in amphetamine-induced hyperlocomotion, and altered gut microbiome. We also studied the neurophysiological properties of the MIA ferrets in development by in-vivo recordings of the local field potential (LFP) from visual cortex in five- to six-week-old animals, and found that the spontaneous and sensory-evoked LFP had decreased power, especially in the gamma frequency band. Overall, our results provide the first evidence for the detrimental effect of MIA in ferrets and support the use of the ferret as an intermediate model species for the study of disorders with neurodevelopmental origin.