Ferrets as a model for investigating the impact of chemical agents on cerebral cortical sulcogyrogenesis.

Gyrencephalic features of the cerebral cortex have been documented in many mammals, exhibiting unique species-related patterns, and are disturbed in individuals with neurodevelopmental and/or psychiatric disorders, including autism spectrum disorder. This mini-review article provides an overview of a series of studies that have investigated sulcogyral developmental alteration as the outcome of two chemical agents with the potential to cause autism spectrum disorder, valproic acid (VPA) and lipopolysaccharide (LPS), using ferrets, which are gyrencephalic animals. Ferret pups received an injection of VPA (200 μg/g body weight) or LPS (500 μg/g of body weight) at 6 and 7 days of postnatal ages. VPA acts on the subventricular zone progenitors, including basal radial glia, to promote their differentiative division, resulting in shallow sulcal infolding in the rostrovental and medial cortices, while enhancing sulcal infolding in the dorsolateral cortex. In contrast, the apoptosis of cortical neurons derived from postproliferative subventricular zone progenitors in neonatally LPS-exposed ferrets may be involved in an anterior shift of the primary sulci located on the medial and dorsolateral cortices. These two agents affect subventricular zone progenitors differently, leading to distinct gyrification abnormality patterns. These findings suggest that the ferret is an advantageous animal model for elucidating the pathogenesis of neurodevelopmental and/or psychiatric disorders in terms of gyrification abnormalities raised by chemical agents.