Sex-dependent effects of rat maternal immune activation on motor function in offspring of poly I:C treated rats.

Abstract

A majority of people with schizophrenia will experience motor symptoms such as impairments to coordination, balance and motor sequencing. These neurological soft signs are associated with negative social and functional outcomes, and poor disease prognosis. They occur prior to medication exposure, suggesting they are an intrinsic feature of schizophrenia. Despite the need to better understand this dysfunction, relatively few studies have provided a detailed focus on motor capability in animal models of schizophrenia. Here we investigate motor coordination in a rat maternal immune activation (MIA) model of schizophrenia risk. The female and male offspring of Polyinosinic:polycytidylic acid (Poly I:C), and vehicle-treated, pregnant dams were tested in a horizontal ladder rung task using regular and irregular rung configurations. We extracted information about limb positions from video, and measured faults and gait coordination in the task. We found that adult male MIA rats were more likely to slip from the ladder rungs than control animals, and they were more likely to have multiple limbs slip simultaneously. MIA rats also exhibited more variability in stride length, a result that correlated with slips and mirrored disease-related changes in human gait. In contrast, female MIA rats displayed minimal alterations in motor performance. Our findings show that the ladder task uncovers sex-dependent effects on motor coordination in MIA rats and highlights the potential usefulness of the MIA model for investigating motor dysfunction in an animal model of schizophrenia risk.