Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment

Guma, Elisa; Bordeleau, Maude; Snook, Emily; Desrosiers-Grégoire, Gabriel; González Ibáñez, Fernando; Picard, Katherine; Spring, Shoshana; Lerch, Jason P.; Nieman, Brian J.; Devenyi, Gabriel A.; Tremblay, Marie-Eve; Chakravarty, M. Mallar

Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental and psychiatric disorders. MIA-induced deficits in adolescent and adult offspring have been well characterized, however, less is known about the effects of MIA-exposure on embryo development. To address this gap, we performed high-resolution ex vivo magnetic resonance imaging (MRI) to investigate the effects of early (gestational day [GD]9) and late (GD17) MIA-exposure on embryo (GD18) brain structure. We identify striking neuroanatomical changes in the embryo brain, particularly in the late exposed offspring. We further examined hippocampal neuroanatomy using electron microscopy and identified differential effects due to MIA-timing. An increase in apoptotic cell density was observed in the GD9 exposed offspring, while an increase in the density of dark neurons and glia, putative markers for increased neuroinflammation and oxidative stress, was observed in GD17 exposed offspring, particularly in females. Overall, our findings integrate imaging techniques across different scales to identify differential impact of MIA-timing on the earliest stages of neurodevelopment.