NURTIENT RESTRICTION: FETAL BABOON BRIAN DEVELOPMENT

营养限制：胎儿狒狒的发育

• 批准号: 8129571
• 负责人: THOMAS Joseph MCDONALD
• 金额: $ 8.27万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8129571
• 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; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Intervention; Investigation; Knowledge; Laboratories; MEKs; Modeling; Mothers; Mus; Nervous system structure; Neuroglia; Neurons; Nutrient; 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; 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.

介绍 绝大多数脑胰岛素样生长因子（IGF）研究都是在啮齿动物模型中进行的。 然而，灵长类动物妊娠期间 (G) 的大部分大脑发育都是在出生后发生的 在实验室啮齿动物中，啮齿动物模型存在明显的缺点[1]。此外，重要的是 强调 Rice 和 Barone 提出的观点“……白化动物的视觉和听觉系统 所有物种均异常；因此，当出现白化病大鼠或小鼠的情况时，白化病大鼠或小鼠是一个糟糕的评估选择。 神经系统很有趣。”[2]。这一非常重要的警告使得在 在假设适用于人类之前，需要先在灵长类动物模型中对大鼠进行验证。本申请 研究 30% 母体 (M) 营养限制 (NR) 对灵长类动物胎儿大脑发育的影响 模型，狒狒。该范例不会导致胎儿体重减轻；然而正如将要展示的那样，它 确实会导致发育中的大脑的许多参数急剧下降。此外，我们的 30% MNR 范式降低胎儿血液尿素氮，从而表明胎儿 NR 并证明体重 胎儿 NR 的一个非常差的指标。我们选择观察额叶皮层，因为它是大脑的一个区域 在啮齿动物模型中已显示，即使相对温和（等热量，三分之二 较少的蛋白质）营养限制[3]，我们希望确定是否会在灵长类动物中看到类似的结果 模型。此外，我们认为该领域的自然资源保护效应将反映在其他领域的损害中，例如 作为小脑，因此，我们将保留其他大脑区域用于未来的研究。对此的调查 道德上不能在人类身上进行类型化；这一事实使得研究的大脑模型类似于 人类如狒狒，就更急了。如果没有该领域的知识，诊断程序和 无法设计治疗缺陷的疗法，也无法规划积极干预的策略。