Environmental impacts on the developing CNS: CD15, NCAM-L1, and GFAP expression in rat neonates exposed to hypergravity

Advances in Space Research

2006

Self Cite

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.

Section: Introductionmentioning

confidence: 70%

“…The neonatal brains were then rapidly removed and the cerebella were dissected out (Nguon et al, 2004;Sulkowski et al, 2004). The cerebella were weighed by two independent investigators and rapidly frozen for further analysis.…”

Section: Tissue Collectionmentioning

confidence: 99%

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

Nguon

Ladd

Advances in Space Research

2006

Self Cite

“…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).…”

Section: Gravireaction Of the Mature Cnsmentioning

confidence: 99%

“…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.…”

Section: Gravireaction Of Cns Developing Under Altered Gravitymentioning

confidence: 99%

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

2008

Cerebellum

As man embarks on space exploration and contemplates space habitation, there is a critical need for basic understanding of the impact of the environmental factors of space, and in particular gravity, on human survival, health, reproduction and development. This review summarizes our present knowledge on the effect of altered gravity on the developing CNS with respect to the response of the developing CNS to altered gravity (gravireaction), the physiological changes associated with altered gravity that could contribute to this effect (gravitransduction), and the possible mechanisms involved in the detection of altered gravity (graviperception). Some of these findings transcend gravitational research and are relevant to our understanding of the impact of environmental factors on CNS development on Earth.

“…Their brains were then rapidly removed and the cerebella were dissected from the brain stem, weighed, frozen in methyl butane (Nguon et al, 2004;Sulkowski et al, 2004), and stored at −80°C for further analysis.…”

Section: Animals and Treatmentmentioning

confidence: 99%

Potential role of oxidative stress in mediating the effect of altered gravity on the developing rat cerebellum

Advances in Space Research

Nguon

Sulkowski

et al. 2007

We have 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 exposure to hypergravity results in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. To test this hypothesis we compared cerebellar oxidative stress marker 3-nitrotyrosine (3-NT; an index of oxidative protein modification) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG; an index of oxidative DNA damage) between stationary control (SC) and rat neonates exposed to 1.65 G (HG) on a 24-ft centrifuge from gestational day (G) 8 to P21. The levels of 3-NT and 8-OH-dG were determined by specific ELISAs. We also compared the Purkinje cell number (stereorologically) and rotarod performance between the two groups. The levels of 3-NT were increased only in HG females on P6 and on P12 in the cerebellum, and only in HG females on P12 in the extracellabellar tissue. Limited cerebellar data suggests an increase in the levels of 8-OH-dG on P12 only in HG females. In extracerebellar tissue the increase in 8-OH-dG levels was observed in both HG males and HG females except on P6 when it was only observed in HG males. While preliminary, these data suggest that the effect of hypergravity on the developing brain is sexdependent and may involve oxidative stress. Oxidative stress may, in turn, contribute to the decrease Purkinje cell number and impaired motor behavior observed in hypergravity-exposed rats.