Leptin prevents cognitive impairment in a rat model of postnatal growth restriction (137.4)

Abstract

PGR is associated with impaired neurodevelopment, and lower serum leptin in preterm infants. We have demonstrated the same in a rodent model. As leptin is important in CNS myelination, we hypothesized that leptin is causally related to poorer neurodevelopment in PGR. Using our previous model, newborn rats were randomized to litters of 10/dam (N, Normal, n=70) or 18/dam (PGR, n=108) until weaning (d21). Between d8‐14, half the pups in each litter were randomized to 3 ug/kg/d rat leptin s.c., half to PBS. After weaning, a high‐fat rodent chow was fed ad libitum to d75. All rats had glucose tolerance and insulin stimulation tests, as well as cognition (spontaneous alternation in a T‐maze) assessed. PGR rats were 30% smaller than N rats from d5‐21 (p<0.0001). Female PGR rats caught‐up with N rats by d75, but male PGR rats remained 15% smaller. Leptin administration increased serum leptin levels but did not affect growth. In PBS‐treated rats, neurodevelopment was worse in PGR (5.5 ±1.2) than N rats (7.0 ±0.8, p<0.0001). Leptin improved neurodevelopment in PGR (7.0 ±1.0, p<0.0001) but not N rats (7.2 ±1.2, p=NS). PGR rats had improved glucose tolerance (p=0.015) and insulin sensitivity (p=0.0001), but leptin had no effect. Leptin reversed cognitive impairment in rats with PGR, without adverse effects on growth, insulin sensitivity, or glucose tolerance. This model and findings merit further investigation in preterm infants.