新生儿缺氧可能会干扰大鼠的生长和长期代谢稳态。为了便于代谢评估,受试者通常被单独安置。然而,与个体居住条件相关的社会隔离改变了动物行为,这可能会影响实验结果。这项研究调查了社会隔离对新生儿缺氧引起的生长和能量代谢变化的影响。雄性和雌性Wistar大鼠暴露在外,出生后第2天(P2),25分钟的缺氧或对照治疗。从P27开始,每组的一部分受试者被隔离在标准笼子里,其余受试者分组。在P34或P95时,受试者禁食18小时,补料1小时,然后灌注30分钟后。血糖,瘦素,胰岛素,在两个年龄段都评估了胰腺的形态。对于以P95灌注的受试者,记录体重和食物摄入量直至P90,并收集大脑进行Fos和NeuN免疫组织化学。结果表明,尽管食物摄入量没有变化,但暴露于新生儿缺氧和社会隔离的雄性大鼠的体重增加增加。此外,社会隔离(1)减少禁食后体重减轻和禁食后食物摄入和(2)增加血糖,胰岛素,以及暴露于缺氧和对照治疗的雄性和雌性大鼠的瘦素水平,在P35和P95。此外,尽管在P35时,缺氧会增加男性的胰岛素水平,它减少了女性胰腺中β阳性细胞的面积。在P95时,缺氧会增加男性餐后体重减轻,禁食后的食物摄入,胰岛素,和瘦素,男性和女性弓状核(ARC)中的Fos表达降低。饮食过度与可能的瘦素和胰岛素抵抗有关,怀疑这些激素的高循环水平和ARC的神经元激活不良。这项研究表明,与断奶的持续社会隔离会改变,以差异化的方式,暴露于新生儿缺氧甚至对照治疗的雄性和雌性Wistar大鼠的长期能量代谢和生长。因此,社会隔离应被视为对实验结果和新生儿损伤结局产生负面影响的因素。这些结果也应考虑到临床程序,因为使用的模型模拟早产儿的条件和一些治疗方法需要隔离。
Neonatal oxygen deficiency in rats may disturb growth and long-term metabolic homeostasis. In order to facilitate metabolic evaluation, the subjects are usually housed individually. However, social isolation associated with individually housed conditions alters animal behavior, which may influence the experimental results. This study investigated the effects of social isolation on neonatal
anoxia-induced changes in growth and energy metabolism. Male and female Wistar rats were exposed, on postnatal day 2 (P2), to either 25-min of
anoxia or control treatment. From P27 onward, part of the subjects of each group was isolated in standard cages, and the remaining subjects were housed in groups. At P34 or P95, the subjects were fasted for 18 h, refeed for 1 h, and then perfused 30 min later. Glycemia, leptin, insulin, and morphology of the pancreas were evaluated at both ages. For subjects perfused at P95, body weight and food intake were recorded up to P90, and the brain was collected for Fos and NeuN immunohistochemistry. Results showed that male rats exposed to neonatal
anoxia and social isolation exhibited increased body weight gain despite the lack of changes in food intake. In addition, social isolation (1) decreased post-fasting weight loss and post-fasting food intake and (2) increased glycemia, insulin, and leptin levels of male and female rats exposed to anoxia and control treatments, both at P35 and P95. Furthermore, although at P35,
anoxia increased insulin levels of males, it decreased the area of the β-positive cells in the pancreas of females. At P95,
anoxia increased post-prandial weight loss of males, post-fasting food intake, insulin, and leptin, and decreased Fos expression in the arcuate nucleus (ARC) of males and females. Hyperphagia was associated with possible resistance to leptin and insulin, suspected by the high circulating levels of these hormones and poor neuronal activation of ARC. This study demonstrated that continuous social isolation from weaning modifies, in a differentiated way, the long-term energy metabolism and growth of male and female Wistar rats exposed to neonatal anoxia or even control treatments. Therefore, social isolation should be considered as a factor that negatively influences experimental results and the outcomes of the neonatal injury. These results should also be taken into account in clinical procedures, since the used model simulates the preterm babies\' conditions and some therapeutic approaches require isolation.