Preterm birth is associated with impairment to the inhibitory GABAergic system, affecting inhibitory/excitatory balance, increasing vulnerability to neurobehavioral conditions (ADHD and anxiety). We hypothesize that a premature loss of in-utero exposure to inhibitory neurosteroids provided by the placenta, is responsible for GABAergic impairment. This study aims to determine changes in GABA/glutamate balance in the cerebellum following preterm birth.
Time-mated Dunkin Hartley guinea pigs were delivered either preterm (induced at GA62) or term (spontaneous at ~GA69) and allocated to neonatal or juvenile collection. Preterm born neonates were maintained until term equivalent age (TEA) whilst cerebellums of term born neonates were collected 24hrs post-delivery. Tissues from term born juveniles were collected 40 days post-delivery and preterm born juveniles were collected at corrected 40 days post-delivery (TEA+40 days). RT-PCR analysis of cerebellums was performed using the JUNO and BIOMARK instruments to quantify changes in the expression of GABAergic and Glutamatergic pathway components.
Expression of the GABAA receptor α6 subunit (GABRA6) was lower in preterm neonates than preterm juveniles (males p=0.0018) (females p=0.0062) but this difference was not observed in term cohorts. Preterm juvenile females had higher expression of excitatory glutamate receptors (GRIA4, GRM5, GRIA1) than term born (p=0.0004, p=0.0422, and p=0.0199 respectively).
Preterm birth induces changes in receptors involved in excitatory/inhibitory balance in the cerebellum with changes differing between sexes and continuing to the equivalent of childhood. As the cerebellum has important roles in cognitive processes, the ongoing alterations in GABA/glutamate pathways may increase the risk of developing ADHD-like and anxiety disorders in these infants and represent targets for treatment options to improve outcomes.