Neuroanatomical alterations in higher-order thalamic nuclei of fetuses with Down syndrome

Analyses of fetal brain tissue indicate that there are fewer proliferating cells, as measured by expression of the cell cycle marker Ki67 and of cyclin proteins, in the germinal zones of the hippocampus and cortex in Down syndrome.

“Analyses of fetal brain tissue indicate that there are fewer proliferating cells, as measured by their expression of the cell cycle marker Ki67 and of cyclin proteins, in the germinal zones of the hippocampus and cortex in DS40,42–44,47,50,64.”

The presence of fewer cycling cells and the reduced number of progenitors both support the suggestion that neurogenesis is reduced during development in Down syndrome, although these data do not distinguish between slower progenitor proliferation or premature progenitor cell cycle exit.

“Together, the presence of fewer cycling cells and the reduced number of progenitors both support the suggestion that neurogenesis is reduced during development in DS, although these data do not distinguish between slower progenitor proliferation or premature progenitor cell cycle exit.”

A third study found no difference in the density of interneurons in thalamic nuclei of fetuses (17-21 weeks gestation) with Down syndrome compared to those without.

“A third study also found no difference in the density of interneurons in thalamic nuclei of fetuses (17–21 weeks gestation) with DS compared to those without (Stagni et al., 2020).”

Reductions in the number of proliferating neural progenitor cells in the dentate gyrus, germinal matrix of the lateral ventricle, and third ventricle have been observed in tissue derived from fetuses diagnosed with Down syndrome (17-21 weeks gestation) prior to the initial observations of volumetric changes.

“Reductions in the number of proliferating neural progenitor cells (NPCs) in the dentate gyrus, germinal matrix of the lateral ventricle, and third ventricle have all been observed in tissue derived from fetuses diagnosed with DS (17–21 weeks gestation) prior to the initial observations of volumetric changes (Contestabile et al., 2007; Stagni et al., 2020).”

During 17-21 weeks gestation, fewer neurons were found in the hippocampus, cerebellum, and multiple thalamic nuclei in fetuses with Down syndrome.

“During the same time period (17–21 weeks gestation) fewer neurons were found in the hippocampus (Guidi et al., 2008), cerebellum (Guidi et al., 2011), and multiple thalamic nuclei (Stagni et al., 2020).”

Human studies show decreased cerebral volume due in part to hypocellularity driven by decreased NPC proliferation.

“One of the best documented phenotypes observed from human studies is the decreased cerebral volume thought to be due in part to hypocellularity driven by a decrease in NPC proliferation (Contestabile et al., 2007; Stagni et al., 2020).”

In fetuses with Down syndrome, there was a significant decrease in density of excitatory neurons, and the proportion of interneurons to excitatory neurons was significantly increased.

“However, because this same study identified a significant decrease in density of excitatory neurons, the proportion of interneurons to excitatory neurons was significantly increased in fetuses with DS.”