Preterm Birth Alters the Maturation of the GABAergic System in the Human Prefrontal Cortex

Developmental changes in GABAergic and glutamatergic systems during frontal lobe development have been hypothesized to play a key role in neurodevelopmental disorders seen in children born very preterm or at/with low birth weight, but the associated cellular changes have not yet been identified. Here we studied the molecular development of the GABAergic system specifically in the dorsolateral prefrontal cortex, a region that has been implicated in neurodevelopmental and psychiatric disorders. The maturation state of the GABAergic system in this region was assessed in human post-mortem brain samples, from term infants ranging in age from 0 to 8 months (n = 17 male, 9 female). Gene expression was measured for 47 GABAergic genes and used to calculate a maturation index. This maturation index was significantly more dynamic in male than female infants. To evaluate the impact of premature birth on the GABAergic system development, samples from 1-month-old term (n = 9 male, 4 female) and 1-month corrected-age very preterm (n = 8 male, 6 female) infants, were compared using the same gene list and methodology. The maturation index for the GABAergic system was significantly lower (-50%, p < 0.05) in male preterm infants, with major alterations in genes linked to GABAergic function in astrocytes, suggesting astrocytic GABAergic developmental changes as a new cellular mechanism underlying preterm brain injury.

Automated summary

Developmental changes in the GABAergic and glutamatergic systems in the frontal lobe are believed to be important in neurodevelopmental disorders seen in very preterm or low birth weight children. This study focused on the molecular development of the GABAergic system in the dorsolateral prefrontal cortex, finding that the maturation state of this system was more dynamic in male infants. Premature birth was also found to have a significant impact on the GABAergic system development, particularly in male infants, suggesting a new cellular mechanism underlying preterm brain injury.