Poster abstracts

Poster number 72 submitted by Michaela Breach

Prenatal allergic inflammation in rats programs the developmental trajectory of dendritic spine patterning in brain regions associated with cognitive and social behavior

Michaela R. Breach (NGP), Courtney N. Dye (NGP), Anabel Galan (Dept. of Psychology, Ohio State University), Brooke J. Schatz (Dept. of Psychology, Ohio State University), Kathryn M. Lenz, PhD (Dept. of Psychology, Dept. of Neuroscience, Ohio State University)

Abstract:
Maternal inflammation during pregnancy increases the risk for neurodevelopmental disorders in offspring (1,2) Neurodevelopmental disorders are associated with immune dysregulation and neuroglial abnormalities (3). Rodent models of maternal immune activation (MIA) are useful for understanding potential mechanisms underlying neurodevelopmental disorders and their symptoms. We previously found that allergic MIA in rats alters microglia and mast cell number in the brain and produces abnormal social behavior, hyperlocomotion, and cognitive inflexibility in offspring (4). Given that synaptic changes often accompany such behavioral phenotypes and given that immune cells regulate developmental synaptic patterning, we hypothesized that dendritic spine density may be altered in allergic MIA offspring. Here, we employed our model of prenatal allergic inflammation and examined dendritic spine density throughout development. Adult female rats were sensitized to ovalbumin (OVA) with Alum adjuvant prior to breeding. On gestational day 15, pregnant dams were challenged with intranasal administration of OVA to elicit allergic inflammation. Controls were administered saline under the same regimen. Brain tissue was collected from male and female offspring on postnatal days (P)5, 15, 30 and in adulthood and processed for Golgi-Cox staining. Multiple brain regions that govern cognition and social behavior were examined: the medial prefrontal cortex (mPFC), striatum, septum, nucleus accumbens (NAc), and amygdala. Allergic MIA reduced spine density throughout development in the mPFC, and this reduction was normalized by adulthood. MIA-induced reductions in spine density were also found in the NAc (shell and core) and medial amygdala at P30, while a sex-specific effects were found in the septum. Additionally, MIA reduced spine density in the medial and basolateral amygdala of adult offspring. These dendritic spine reductions across brain regions involved in cognitive and social function provide a basis for future intervention studies targeted at rescuing spine deficits via immunomodulatory treatment.

References:
1: Instanes, J. T., Halmøy, A., Engeland, A., Haavik, J., Furu, K., & Klungsøyr, K. (2017). Attention-Deficit/Hyperactivity Disorder in Offspring of Mothers With Inflammatory and Immune System Diseases. Biological Psychiatry, 81(5), 452–459.

2: Brown, A. S. (2012). Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism. Developmental Neurobiology, 72(10), 1272–1276.

3: Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Annals of Neurology, 57(1), 67–81.

4: Breach et al., (accepted) Maternal allergic inflammation in rats impacts the offspring perinatal neuroimmune milieu and the development of social play, locomotor behavior, and cognitive flexibility. Brain Behavior and Immunity.

Keywords: dendritic spines, maternal inflammation, microglia