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We have previously reported that the developmental exposure of rats to altered gravity (1.65 g) from gestational day 8 to postnatal day 21 impacts motor functions and cerebellar structure. The present study examined whether the decrease in cerebellar mass accompanied by impaired performance on a rotorod in hypergravity-exposed rats was related to a decrease in Purkinje cell number. The total number of Purkinje cells was determined on postnatal day 21 using a stereological analysis applied to paraformaldehyde-fixed cerebellar samples subsequently embedded in celloidin. Total Purkinje cell number was decreased by 17.7-25.3%. These results imply that exposure to altered gravity during Purkinje cell birth may affect their proliferation, resulting in a decrease in Purkinje cell number, which, in turn, leads to motor impairment.

We previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that neonatal cerebellar structure and motor coordination may be particularly vulnerable to the effects of hypergravity during specific developmental stages. To test this hypothesis, we compared neurodevelopment, motor behavior and cerebellar structure in rat neonates exposed to 1.65 G on a 24-ft centrifuge during discrete periods of time: the 2 nd week of pregnancy [gestational day (G) 8 through G15; group A], the 3 rd week of pregnancy (G15 through birth on G22/G23; group B), the 1 st week of nursing [birth through postnatal day (P) 6; group C], the 2 nd and 3 rd weeks of nursing (P6 through P21; group D), the combined 2 nd and 3 rd weeks of pregnancy and nursing (G8 through P21; group E) and stationary control (SC) neonates (group F). Prenatal exposure to hypergravity resulted in intrauterine growth retardation as reflected by a decrease in the number of pups in a litter and lower average mass at birth. Exposure to hypergravity immediately after birth impaired the righting response on P3, while the startle response in both males and females was most affected by exposure during the 2 nd and 3 rd weeks after birth. Hypergravity exposure also impaired motor functions, as evidenced by poorer performance on a rotarod; while both males and females exposed to hypergravity during the 2 nd and 3 rd weeks after birth performed poorly on P21, male neonates were most dramatically affected by exposure to hypergravity during the second week of gestation, when the duration of their recorded stay on the rotarod was one half that of SC males. Cerebellar mass was most reduced by later postnatal exposure. Thus, for the developing rat cerebellum, the postnatal period that overlaps the brain growth spurt is the most vulnerable to hypergravity. However, male motor behavior is also affected by midpregnancy exposure to hypergravity, suggesting discrete and sexually dimorphic windows of vulnerability of the developing central nervous system to environmental perturbations.

No 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.