Exposure to altered gravity during specific developmental periods differentially affects growth, development, the cerebellum and motor functions in male and female rats

Abstract

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.

Cerebellum and Gravity: Altered Earth’s Gravity Perception Under Pathological Conditions and Response to Altered Gravity in Space

“…The effect was further exacerbated by an increase in gravity with latency of falling at 1.75 G, being one tenth of that of the stationary control pups (Nguon et al 2006a). The effect of hypergravity on motor behavior was also strongly dependent on the specific developmental stage at which the exposure occurred (Nguon et al 2006b), and was most dramatic following postnatal exposure, with males being most dramatically affected by exposure during the second week of gestation (Nguon et al 2006b) that corresponds to the time of Purkinje cell birth. Furthermore, hypergravity exposure resulted in decreased cerebellum mass that was exacerbated at higher G forces, and the effect was more dramatic in male neonates (Nguon et al 2006a).…”

“…Comparison of different gravity loadings and suggested that 1.65 G as the maximum practical gravity level for perinatal G8-P21 exposure (Ladd et al 2006). Further studies identified critical periods of gravity exposure (Nguon et al 2006b); hypergravity exposure during the critical period of brain development (birth-P6) had a most dramatic effect on neurotrophin expression with a decrease in BDNF and NGF expression (Sajdel-Sulkowska et al 2009). …”

Ground-Based Researches on the Effects of Altered Gravity on Mice Development

“…The vestibular nuclei of rats that developed in space showed a marked reduction in the size of neuronal cell bodies and a pronounced reduction in the growth and branching of their dendrites, with poor cerebellar projections in the various parts of the vestibular nuclei at the various stages of development (Raymond et al 2000). Cerebellar structures also seem to be altered in rats conceived and born in HG (Ladd et al 2006;Nguon et al 2006a, b). At the level of the spinal cord, HG induced strong perturbations and a delay in the development of monoaminergic projections (Gimenez y Ribotta et al 1998).…”

Brain development, environment and sex: what can we learn from studying graviperception, gravitransduction and the gravireaction of the developing CNS to altered gravity?

“…This is suggested by observations that prenatal exposure of rats to microgravity affects the righting response (15) and motor and equilibrium behavior that are associated with structural changes in the brain (16). Cerebellar abnormalities are frequently associated with deficits in motor functions (17) and cerebellar abnormalities have been observed both under microgravity and hypergravity (18)(19)(20)(21)(22)(23)(24)(25).…”

“…Another system employs hypergravity (27)(28), which can be generated on a centrifuge (29). In particular, the large-radius centrifuge at Ames Research Center provides an ideal system to perform large-scale and long-term developmental studies (19)(20)(21)(22)(23)(24)(25). Serova (30) compared the effects of microgravity and 2G hypergravity on various developmental phases of rats; she concluded that hypergravity is a good model to evaluate the potential effect of reduced gravity during space flights.…”