Chronic Glucocorticoid Effects in Prefrontal Cortex

前额皮质的慢性糖皮质激素作用

基本信息

批准号：
6891832
负责人：
CARA L WELLMAN
金额：
$ 7.53万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-06-01 至 2007-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6891832
关键词：
behavioral /social science research tag behavioral extinction cell morphology corticosteroid inhibitor corticosteroid receptors dendrites fear glucocorticoids hormone regulation /control mechanism laboratory rat physiologic stressor prefrontal lobe /cortex psychological stressor pyramidal cells tissue /cell preparation

项目摘要

DESCRIPTION (provided by applicant): Chronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. For example, both stress and chronic administration of corticosterone produce dendritic atrophy in hippocampal neurons. Prefrontal cortex is also a target for glucocorticoids involved in the stress response shows neurochemical changes in response to stress and plays a role in many of the cognitive processes that undergo stress-induced alterations. Thus, changes in prefrontal cortex may mediate some stress- and glucocorticoid-induced cognitive deficits. To determine if glucocorticoid-induced morphological changes also occur in medial prefrontal cortex, I assessed the effects of chronic corticosterone administration on dendritic morphology in this corticolimbic structure. Previously, I demonstrated that chronic corticosterone administration resulted in a significant redistribution of apical dendrites of lamina II-III pyramidal neurons in medial prefrontal cortex of rats: amount of dendritic material proximal to the soma was increased, while distal dendritic material was decreased relative to controls. The experiments proposed here will lay the groundwork necessary to begin to assess the functional significance and mechanisms of this dendritic reorganization. To determine the minimum duration of chronic mild stress necessary to alter the structure of pyramidal neurons in medial prefrontal cortex, I will assess the effects of varying durations of chronic restraint stress on dendritic arborization of layer II-III pyramidal neurons in medial prefrontal cortex. To determine whether stress-induced changes in prefrontal cortex are mediated by corticosterone, I will assess whether administration of a corticosterone blocker prevents stress-induced changes in dendritic morphology of layer II-III pyramidal neurons in medial prefrontal cortex. Finally, to determine whether stress alters a prefrontally mediated behavior, I will assess the effect of chronic restraint stress on extinction of fear conditioning

描述（由申请人提供）：慢性应激会导致认知缺陷，并伴随着神经化学和形态的改变。例如，胁迫和慢性给药皮质酮在海马神经元中产生树突状萎缩。前额叶皮层也是涉及应力反应的糖皮质激素的靶标，显示了应激反应的神经化学变化，并且在许多经历压力引起的改变的认知过程中起作用。因此，前额叶皮层的变化可能介导一些应力和糖皮质激素引起的认知缺陷。为了确定糖皮质激素诱导的形态变化是否也发生在内侧前额叶皮层中，我评估了慢性皮质酮给药对这种皮质细胞结构中树突状形态的影响。以前，我证明，慢性皮质酮给药导致大鼠内侧前额叶皮层中层II-II-III-III锥体神经元的顶端树突的显着重新分布：与对照组相对，远端树突状材料的近端树突状材料量增加，而远端树突状材料则增加了。这里提出的实验将奠定必要的基础，以开始评估该树突重组的功能意义和机制。为了确定改变内侧前额叶皮层中锥体神经元结构所必需的慢性轻度应激持续时间，我将评估慢性约束应激的不同持续时间对内侧前额叶皮层中II-IIII III III层神经元的树突状树突的影响。为了确定压力诱导的前额叶皮层变化是否是由皮质酮介导的，我将评估施用皮质酮阻滞剂是否可以防止内侧前额叶皮质中的II-II-III层锥体神经元的树突形态变化。最后，为了确定压力是否改变了前额叶介导的行为，我将评估慢性约束应力对恐惧条件灭绝的影响