PS-69
Title: A Rat Model of Maternal Immune Activation
Authors: Katherine Ku, Milo Careaga, Carolyn Chang, Alex Chiang, Robert F. Berman, Melissa Bauman
Introduction: Infection during pregnancy increases the probability of offspring later being diagnosed with a neurodevelopmental disorder such as autism or schizophrenia. However, not all women exposed to infection during pregnancy have a child with altered neurodevelopment. The intensity and timing of the maternal immune response, combined with genetic susceptibility and postnatal risk factors, may be informative for linking prenatal environment with abnormalities of postnatal brain development and behavior. Our present study focuses on how different forms of polyriboinosinic-polyribocytidylic acid (PolyIC) can affect the intensity of the maternal immune response by comparing high (HMW) and low (LMW) molecular weights of the viral mimic.
Methods: Pregnant rats received tail vein injections on gestational day 15 with PolyIC-HMW, PolyIC-LMW, or saline. Cytokine levels were measured by taking blood draws at 3, 4.5, and 6 hour time points following injections. Blood sera were analyzed for
Il-1β, Il-6, Il-10, and TNF-α. Sickness behaviors were assessed in the pregnant rats during the 24-hour period following injection, using the Columbus Instruments Comprehensive Lab Animal Monitoring System (CLAMS). The male offspring were assessed at juvenile, young adult and adult time points (PND26-110) for the following behaviors: anxiety, sociability, locomotion, pre-pulse inhibition, and reciprocal social interactions. Following behavior testing, cell density and paravalbumin expression were assessed in the CA-1 and CA-3 regions of the hippocampus.
Results: Our preliminary results indicate that different forms of PolyIC can yield dramatically different cytokine responses and sickness behaviors. The behavioral and histological impact of these two forms of PolyIC on the offspring is currently being investigated.
Discussion: These novel findings are critical to understanding the mechanism underlying the MIA model and may explain variability in previous studies.