Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy

Abstract

Maternal infection during prenatal life is a risk factor for neurodevelopmental disorders, including schizophrenia and autism, in the offspring. We and others have reported white mater microstructure abnormalities in prefrontal–striato-temporal networks in these disorders. In addition we have shown that early rather than late maternal immune challenge in the mouse model precipitates ventricular volume change and impairs sensorimotor gating similar to that found in schizophrenia. However, it is not known whether the timing of maternal infection has a differential impact upon white matter microstructural indices. Therefore this study directly tested the effect of early or late gestation maternal immune activation on post-natal white matter microstructure in the mouse. The viral mimic PolyI:C was administered on day 9 or day 17 of gestation. In-vivo diffusion tensor imaging (DTI) was carried out when the offspring reached adulthood. We describe a novel application of voxel-based analysis to evaluate fractional anisotrophy (FA). In addition we conducted a preliminary immunohistochemical exploration of the oligodendrocyte marker, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), to determine whether differences in myelination might contribute to any changes in FA observed. Our results provide experimental evidence that prenatal exposure to inflammation elicits widespread differences in FA throughout fronto-striatal–limbic circuits compared to control saline exposure. Moreover, FA changes were more extensive in the group exposed earliest in gestation.