Estrogen could promote brain cortical development in preterm infants

Premature birth alters the balance of interneurons in the cerebral cortex that can be restored with estrogen treatment, according to a study of human brain tissue and preterm rabbits published in J Neurosci.

Infants born prior to a full-term pregnancy are at increased risk of neurobehavioral disorders linked to defects in interneurons, which continue to develop through the end of the third trimester. Prematurity is also associated with a large reduction in levels of the hormone estrogen.

Studying the development of interneurons from brain samples of deceased, premature-born human infants, reearchers identified abnormalities in the distribution of interneuron subtypes. The researchers further show that exposure to estrogen corrected these imbalances in prematurely delivered rabbits.

The parvalbumin⁺ and calretinin⁺ neurons were abundant, whereas somatostatin⁺ and neuropeptide-Y⁺neurons were few in cortical layers of human infants. Premature birth of infants reduced the density of parvalbumin⁺ or GAD67⁺ neurons and increased somatostatin⁺ interneurons in the upper cortical layers.

Importantly, 17-β-estradiol treatment in preterm rabbits increased the number of parvalbumin⁺ neurons in the upper cortical layers relative to controls at postnatal days 14 and 21, and transiently reduced somatostatin population at day 14.

Moreover, protein and mRNA levels of Arx, a key regulator of cortical interneuron maturation and migration, were higher in estrogen-treated rabbits relative to controls.

This study suggests that mimicking the in utero environment, where the fetus would usually be exposed to maternal hormones, has the potential to improve developmental outcomes for preterm infants.