NURTIENT RESTRICTION: FETAL BABOON BRIAN DEVELOPMENT

营养限制：胎儿狒狒的发育

• 批准号: 8320794
• 负责人: THOMAS Joseph MCDONALD
• 金额: $ 11.53万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8320794
• 关键词: Affect; Animals; Apoptotic; Area; Auditory system; Blood Urea Nitrogen; Body Weight; Body Weight decreased; Brain; Cerebellum; Development; Diagnostic Procedure; Diet; Differentiation and Growth; Disadvantaged; Environment; Fetus; Future; Gestational Age; Glucose Transporter; Human; IGFBP1 gene; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Intervention; Investigation; Kidney; Knowledge; Laboratories; MEKs; Modeling; Mothers; Nervous system structure; Neuroglia; Neurons; Nutrient; Outcome; Papio; Pathway interactions; Perinatal Exposure; Peripheral; Phosphotransferases; Plasma; Pregnancy; Primates; Protein-Serine-Threonine Kinases; Proteins; Ras homolog enriched in brain; Ras/Raf; Rattus; Rice; Rodent; Rodent Model; Somatomedins; Synapses; System; Visual system structure; albino mouse; albino rat; caspase-9; design; detection of nutrient; feeding; fetal; fetal blood; frontal lobe; human FRAP1 protein; interest; mTOR protein; member; myelination; neurogenesis; response; synaptogenesis

Introduction The vast majority of brain insulin-like growth factor (IGF) studies have been done in rodent models. However, the fact that much of brain development that goes on during gestation (G) in primates occurs postnatally in laboratory rodents is a clear disadvantage in rodent models [1]. In addition, it is important to emphasize a point made by Rice and Barone that"... both the visual and auditory systems of albino animals of all species are abnormal; therefore, albino rats or mice are a poor choice for assessment when the nervous system is of interest." [2]. This very important caveat makes it imperative that observations made in rats be confirmed in a primate model prior to assuming applicability to humans. The present application looks at the effects of 30% maternal (M) nutrient restriction (NR) on fetal brain development in a primate model, the baboon. The paradigm does not produce weight loss in the fetus; however as will be shown, it does produce dramatic reductions in many parameters in the developing brain. In addition, our 30% MNR paradigm reduces fetal blood urea nitrogen thus suggesting fetal NR and demonstrating that body weight is a very poor indicator of fetal NR. We have chosen to look at the frontal cortex since it is an area of the brain that has been shown in rodent models to be adversely affected by even relatively mild (isocaloric, two thirds less protein) nutrient restriction [3] and we wish to determine if a similar result will be seen in a primate model. In addition, we believe that NR effects in this area will be mirrored by detriments in other areas such as the cerebellum and accordingly, we will retain other brain areas for future studies. Investigations of this type cannot ethically be done in humans; this fact makes studies in a model with a brain that is similar to humans such as the baboon, all the more urgent. Without knowledge in this area, diagnostic procedures and therapies for deficits cannot be designed and strategies for pro-active interventions cannot be planned.

引言 绝大多数脑胰岛素样生长因子(IGF)的研究都是在啮齿动物模型上进行的。 然而，事实上，灵长类动物在怀孕(G)期间进行的大部分大脑发育是在出生后发生的 在实验室中研究啮齿动物是啮齿动物模型的一个明显缺点[1]。此外，重要的是要 强调赖斯和巴龙提出的观点，即“……白化动物的视觉和听觉系统 在所有物种中都是不正常的；因此，当白化大鼠或小鼠出现 神经系统是有意义的。“[2]。这一非常重要的警告使得在 在假设适用于人类之前，大鼠在灵长类动物模型中得到确认。本申请 观察30%母体(M)营养限制(NR)对灵长类动物胎儿大脑发育的影响 模特儿，那只狒狒。这一范例不会在胎儿中产生体重减轻；然而，正如将会显示的那样，它 确实会使发育中的大脑中的许多参数急剧减少。另外，我们30%的MNR 范式降低胎儿血尿素氮，从而提示胎儿NR，并证明体重 对于胎儿NR来说，这是一个非常糟糕的指标。我们选择观察额叶皮质，因为它是大脑的一个区域 在啮齿动物模型中已经表明，即使是相对温和的(等卡路里，三分之二)也会对其产生不利影响 较少的蛋白质)营养限制[3]，我们希望确定是否也会在灵长类动物中看到类似的结果 模特。此外，我们认为，这一领域的NR影响将被其他领域的不利影响所反映，例如 作为小脑和相应的，我们将保留其他大脑区域用于未来的研究。对此进行的调查 从伦理上讲，人类不能进行类型化；这一事实使得在大脑类似于 人类如狒狒，更是迫在眉睫。如果没有这方面的知识，诊断程序和 无法设计赤字的治疗方法，也无法规划主动干预的战略。