Developmental regulation of gene expression and astrocytic processes may explain selective hippocampal vulnerability

The hippocampus plays a central role in the brain network that is essential for memory function. Paradoxically, the hippocampus is also the brain structure that is most sensitive to hypoxic-ischemic episodes. Here, we show that the expression of genes associated with glycolysis and glutamate metabolism in astrocytes and the coverage of excitatory synapses by astrocytic processes undergo significant decreases in the CA1 field of the monkey hippocampus during postnatal development. Given the established role of astrocytes in the regulation of glutamate concentration in the synaptic cleft, our findings suggest that a developmental decrease in astrocytic processes could underlie the selective vulnerability of CA1 during hypoxic-ischemic episodes in adulthood, its decreased susceptibility to febrile seizures with age, as well as contribute to the emergence of selective, adultlike memory function.