Sajdel-Sulkowska E M, Li G H, Ronca A E, Baer L A, Sulkowski G M, Koibuchi N, Wade C E
Department of Psychiatry, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Exp Biol Med (Maywood). 2001 Sep;226(8):790-8. doi: 10.1177/153537020222600812.
The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.
本研究考察了超重暴露对发育中大脑的影响,并特别探讨了这些影响是否由甲状腺状态改变介导。34只处于特定孕期的斯普拉格-道利大鼠从妊娠第11天开始持续接受1.5 G(超重,HG)离心处理,直至三个关键发育时间点之一:出生后第(P)6天、P15天或P21天(每只母鼠10只幼崽:5只雄性/5只雌性)。在32天的离心处理期间,静止对照组(SC,n = 25只母鼠)与超重处理的动物饲养在同一房间。在每个时间点评估新生幼崽的体重、前脑和小脑质量以及新生幼崽和母鼠的甲状腺状态。在每个时间点,经离心处理的新生幼崽体重相对较低。在P6时,超重暴露的新生幼崽前脑质量和小脑质量分别最大减少了15.9%和25.6%。新生幼崽血浆分析表明存在短暂的甲状腺功能减退状态,如P6时促甲状腺激素(TSH)水平升高(38.6%)所示,而母鼠血浆TSH水平在P15时最高升高(38.9%)。新生幼崽和母鼠血浆甲状腺激素(TH)水平均未改变,表明存在中度甲状腺功能减退情况。因此,在胚胎期和新生期将发育中的大鼠持续暴露于超重环境对发育中的前脑和小脑以及新生幼崽甲状腺状态有高度显著影响(P < 0.05,经邦费罗尼校正)。这些数据与甲状腺激素在介导超重对发育中的中枢神经系统影响中的假设作用一致,并开始确定TH在发育中的生物体对重力改变的整体反应中的作用。