Abnormal development of the inferior temporal region in fetuses with Down syndrome

Several studies have shown that fewer interneurons are present in the cortex of individuals with Down syndrome than in controls, suggesting that reduced generation of interneurons contributes to the overall reduced neurogenesis in Down syndrome.

“Several studies have shown that fewer interneurons are present in the cortex of individuals with DS44,46,84 than in that of controls, suggesting that reduced generation of interneurons contributes to the overall reduced neurogenesis in DS.”

An increased number of astrocytes has been observed in the frontal lobe, fusiform gyrus, and inferior temporal gyrus of developing fetuses with Down syndrome compared to those without (17-21 weeks).

“An increased number of astrocytes has been observed in the frontal lobe (Zdaniuk et al., 2011), fusiform gyrus, and inferior temporal gyrus (Guidi et al., 2018) of developing fetuses with DS compared to those without (17–21 weeks).”

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.”

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.”

Increased numbers of astrocytes have been reported in the fetal brain in individuals with Down syndrome.

“Increased numbers of astrocytes have been reported in the fetal brain in individuals with DS42,44,99 (Fig. 1).”

The fetal cortex, cerebellum and hippocampus have all been shown to contain fewer neurons in individuals with Down syndrome than in controls, albeit based on small sample sizes.

“The fetal cortex, cerebellum and hippocampus have all been shown to contain fewer neurons in individuals with DS than in controls40–48, albeit based on small sample sizes17.”

The finding of increased calretinin positive interneuron proportion without increases in interneuron number was repeated in the entorhinal cortex and hippocampus in Down syndrome.

“This finding of increased calretinin positive interneuron proportion without increases in interneuron number, was repeated in the entorhinal cortex and hippocampus (Guidi et al., 2018).”

In the cortical plate in the developing fusiform gyrus and inferior temple gyrus (17-21 weeks gestation), there was no significant difference in the number of calretinin positive interneurons between fetuses with Down syndrome and those without, but due to a decrease in number of calretinin negative cells, the proportion of calretinin positive interneurons to the total number of neurons was higher

“There was no significant difference in the number of calretinin positive interneurons between fetuses with DS and those without, but due to a decrease in number of calretinin negative cells, the proportion of calretinin positive interneurons to the total number of neurons was higher in the samples from individuals with DS (Guidi et al., 2018).”