The Development of the External Granular Layer of the Cerebellum and Neurobehavioral Correlates in Neonatal Rats Following Intrauterine and Postnatal Exposure to Caffeine

Abstract

Background:

Caffeine is widely consumed in pregnancy and used therapeutically in preterm babies. Moderately high maternal consumption of caffeine is associated with detrimental neurological effects in the newborn, but there is insufficient information on its effects on the cerebellum in relationship to neurobehavior. We hypothesize that maternal consumption of caffeine will delay the structural and functional development of the cerebellum in offsprings. This study investigates the effect of perinatal maternal caffeine consumption in rats on neurobehavior and the structure of the external granular layer (EGL) in neonates.

Materials and Methods:

Pregnant rats received 50 or 100 mg/(kg/day) of caffeine (designated as CAF 50, CAF 100) by gavage throughout pregnancy and for 3 weeks during lactation. Controls received sterile water. The pups were tested for sensorimotor reflex development, motor coordination, and muscular strength. By serial sacrifice from days 19 to 21, cerebellar development was assessed by measuring the thickness of the EGL and the cellular density in the molecular layer.

Results:

Sensorimotor reflexes and motor coordination appeared earlier in CAF 50 rats than in CAF 100 and controls. Muscular strength was similar to controls in CAF 50, but reduced in CAF 100 rats. The EGL was consistently thicker and number of cells migrating through the molecular layer was higher in the CAF 100 group.

Conclusions:

High maternal caffeine consumption delayed the migration of EGL cells and thus retarded the development of the internal granular layer. We propose that the migration delay and neurobehavioral retardation are related.