Perinatal exposure to polychlorinated biphenyls differentially affects cerebellar development and motor functions in male and female rat neonates

Abstract

Perinatal exposure to polychlorinated biphenyls (PCBs) interacts with genetics and impacts the course of the central nervous system (CNS) development in both humans and animals. To test the hypothesis that the neurobehavioral impairments, and specifically motor dysfunctions following perinatal PCB exposure in rats are associated with changes in a specific brain region, the cerebellum, we compared neurodevelopment, motor behavior, cerebellar structure, and protein expression in rat neonates exposed to the PCB mixture Aroclor 1254 (A1254, 10.0 mg/kg/day) from gestational day 11 until postnatal day (P) 21 with that of controls. Body mass of PCB-exposed pups was not affected at birth, but was significantly lower than that of controls between birth and weaning; by P21 the difference was greater in females than in males. A1254 exposure delayed ear unfolding and impaired performance on the following behavioral tests: (1) righting response on P3-P6; (2) negative geotaxis on P5-P7; (3) startle response on P10-P12; and (4) a rotorod on P12, with PCB-male pups more severely affected than female. Changes in the behavior of PCB pups were associated with changes in cerebellar structure and protein expression. Cerebellar mass was more reduced in PCB-male than PCB-female pups. Analysis of selected cerebellar proteins revealed an increase in GFAP expression, greater in male than in female, and a decrease in L1 expression in both sexes. These results suggest that PCB exposure affects behavior and cerebellar development differently in male and female rat neonates, with greater effects in males. Further studies of neonatal PCB exposure will establish whether the environmental pollutants can contribute to the sex-related preponderance of certain neuropsychiatric disorders.