Cellularity Defects Are Not Ubiquitous in the Brains of Fetuses With Down Syndrome

Down syndrome (DS) is a genetic pathology characterized by various developmental defects. Unlike other clinical problems, intellectual disability is an invariant clinical trait of DS. Impairment of neurogenesis accompanied by brain hypotrophy is a typical neurodevelopmental phenotype of DS, suggesting that a reduction in the number of cells forming the brain may be a key determinant of intellectual disability. Previous evidence showed that fetuses with DS exhibit widespread hypocellularity in brain regions belonging to the temporal lobe memory systems, which may account for the typical explicit memory impairment that characterizes DS. In the current study, we have examined the basal ganglia, the insular cortex (INS), and the cingulate cortex (CCX) of fetuses with DS and age-matched controls (18-22 weeks of gestation), to establish whether cellularity defects involve regions that are not primarily involved in explicit memory. We found that fetuses with DS exhibit a notable hypocellularity in the putamen (-30%) and globus pallidus (-35%). In contrast, no cellularity differences were found in the INS and CCX, indicating that hypocellularity is not ubiquitous in the DS brain. The hypocellularity found in the basal ganglia, which are critically implicated in the control of movement, suggests that such alterations may contribute to the motor abnormalities of DS. The normal cytoarchitecture of the INS and CCX suggests that the alterations exhibited by people with DS in functions in which these regions are involved are not attributable to neuron paucity.