MATERNAL REGULATION OF INFANT PHYSIOLOGY AND BEHAVIOR

婴儿生理和行为的母亲调节

基本信息

批准号：
2246317
负责人：
SEYMOUR LEVINE
金额：
$ 24.7万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-05-01 至 1999-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2246317
关键词：
adrenocorticotropic hormone animal developmental psychology biological models central nervous system child behavior corticosteroid receptors corticotropin releasing factor developmental neurobiology glucocorticoids laboratory rat mother deprivation neuroendocrine system neurogenesis newborn animals pituitary adrenal axis

项目摘要

Glucocorticoids (GCs) have been shown to affect the development and differentiation of a number of tissues. High perinatal GCs act on the developing central nervous system to permanently alter behavior, homeostatic control mechanisms, and the morphology and physiology of the brain. However, most studies in this area have been pharmacological in nature. In the rat, elevating endogenous GC levels during the perinatal period has been difficult, as there are mechanisms during this period, whereby GC levels are maintained at low and constant levels. Between days 4 and 14, pups do not show a GC response to stressors which, in the adult, normally lead to large GC elevations. This period is known as the "stress hyporesponsive period" (SHRP). However, we have recently observed that following 24 hr of maternal deprivation, rat pups show a marked increase in their GC response to stress (novelty) and ACTH administration at ages at which nondeprived pups show none. Using the maternal deprivation paradigm, we can now elevate endogenous GCs during critical periods of development, and thus, study the neuroendocrine and behavioral consequences of these elevated GCs. Stress during pregnancy in the human has been reported to have deleterious effects on the physiological and psychological development of the child. Many neural systems which develop prenatally in the human do so postnatally in the rat. Thus, the neonatal rat may constitute a good animal model in which to study the effects of GCs on these developmental processes. The proposal has four specific aims: 1) To examine which components of the hypothalamic-pituitary-adrenal system (HPA) are modified by maternal deprivation. GCs, ACTH, CRF, and glucocorticoid receptors will be studied during the 24 hr period of maternal deprivation. 2) To examine which aspect of maternal behavior is responsible for inhibiting the HPA system in the rat pup. 3) To examine whether perinatal maternal deprivation influences the subsequent activity of the HPA system and behavior during the pre- and postweaning period. 4) To examine whether perinatal maternal deprivation alters neuroendocrine activity and behavior in adulthood.

糖皮质激素（GC）已被证明会影响发育以及许多组织的分化。高围产期 GC 作用于发育中的中枢神经系统，永久改变行为、稳态控制机制以及形态和大脑的生理学。然而，该领域的大多数研究都具有药理学性质。在大鼠中，提高内源性围产期的 GC 水平一直很困难，因为是在此期间维持 GC 水平的机制处于较低且恒定的水平。在第 4 天到第 14 天之间，幼犬不会显示 GC 对压力源的反应，在成人中，通常会导致到大的 GC 高度。这个时期被称为“压力时期” 低反应期”（SHRP）。然而，我们最近观察到，产妇 24 小时后剥夺后，幼鼠的 GC 反应显着增强压力（新奇）和 ACTH 给药年龄没有被剥夺的幼崽则没有表现出任何迹象。利用母性剥夺范式，我们现在可以在关键时期提高内源性 GC 发育，从而研究神经内分泌和行为这些升高的 GC 的后果。怀孕期间的压力据报道，对人类有有害影响孩子的生理和心理发展。许多人类在出生前发育的神经系统是这样做的大鼠出生后。因此，新生大鼠可能构成良好的动物模型，可用于研究 GC 对这些因素的影响发展过程。该提案有四个具体目标： 1) 审查哪些下丘脑-垂体-肾上腺系统（HPA）的组成部分是因母亲的剥夺而改变。 GC、ACTH、CRF 和将在 24 小时内研究糖皮质激素受体母亲的剥夺。 2）检查母亲的哪些方面行为是抑制大鼠 HPA 系统的原因小狗。 3）检查围产期母亲是否剥夺影响HPA系统的后续活动和行为在断奶前和断奶后期间。 4）检查是否围产期母亲剥夺会改变神经内分泌活动成年后的行为。