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NEURONAL PLASTICITY IN PARAVENTRICULAR NEURONS

室旁神经元的神经可塑性

基本信息

批准号：
2263452
负责人：
DIANE T PIEKUT
金额：
$ 29.58万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-03-01 至 1999-06-30
项目状态：
已结题

项目摘要

The paraventricular nucleus (PVN) of hypothalamus has emerged as an integration and coordination center in hypothalamus for neuroendocrine and autonomic visceral responses and implicates the importance of this nucleus in maintenance of homeostasis. Organisms are often subject to stressors which disrupt the body's homeostasis. Such alterations generate a set of endocrine and neural adaptations that form a stress response with resultant increased levels of pituitary ACTH. The paraventricular nucleus - particularly the CRF-containing neurons - plays a significant role in the neural response to stressful stimuli. The CRF neuron is the nidus and dominant component in the regulation of pituitary ACTH. ACTH regulates the adrenal glucocorticoids and they in turn exert a negative feedback effect on hypothalamus. We propose to elucidate subgroups of CRF-immunoreactive neurons in PVN as identified by their coexpression of a second peptide neurotransmitter. Identification and characterization of these subgroups will provide an anatomical substrate to investigate subsets of neurons that may be differentially and specifically regulated by hormonal feedback and neural inputs, and activated in response to different stress paradigms. Different experimental paradigms of stress have been used to examine neuronal plasticity in the central nervous system. We propose the use of the rat kindling model of epileptic seizure elicitation as a reliable and powerful experimental paradigm to study neuronal plasticity in PVN. Significant advantages of using this model over other paradigms of stress include the unique opportunity to monitor neuronal events in activated PV neurons at well defined stages in the development of kindling. The immunocytochemical detection of c-fos will be used as a tool to identify activated neurons. It is hypothesized that the progressive nature of kindling is accompanied by fundamental anatomical and neurochemical changes. Peptides of particular interest in adaptive responses to stress activation include CRF, vasopressin, oxytocin, enkephalin (ENK) and cholecystokinin (CCK). The expression of these peptides in activated PV neurons at defined stages in kindling development will be analyzed in the proposed experiments. Immunocytochemistry at the light and EM levels and in situ hybridization methodology will be used in these studies. The clinical significance of these studies is also recognized and they will provide new insights on the effects of epileptic seizures on central control of the pituitary- adrenal axis.

下丘脑室旁核（PVN）已成为一个重要的核团，下丘脑神经内分泌整合协调中心和自主内脏反应，并暗示了这一点的重要性，维持内环境稳定。生物体经常受到破坏人体内环境稳定的压力源这样的改变产生一系列内分泌和神经适应，反应，导致垂体ACTH水平升高。的室旁核--尤其是CRF神经元-- 在神经对压力刺激的反应中起着重要作用。 CRF神经元是调节神经元活动的核心和主导成分，垂体ACTH。 ACTH调节肾上腺糖皮质激素，对下丘脑产生负反馈作用。我们建议阐明PVN中CRF免疫反应神经元的亚群，通过共同表达第二种肽类神经递质。这些亚组的识别和表征将提供解剖基板，以研究神经元的子集，可能是差异和具体调节激素反馈和神经输入，并激活响应不同的压力范例。不同的实验范式的压力已被用来检查中枢神经系统的神经可塑性。我们建议使用大鼠点燃模型的癫痫发作的诱发作为一个可靠的和强大的实验范式，研究神经可塑性的PVN。使用这种模式比其他模式的显着优势，压力包括监测神经元事件的独特机会，在发育的明确阶段激活PV神经元引火柴 c-fos的免疫细胞化学检测将作为一种新的检测手段。识别激活的神经元的工具。据推测，点燃的渐进性本质伴随着基本的解剖学特征，和神经化学变化。特别感兴趣的适应性肽对应激激活的反应包括CRF，加压素，催产素，脑啡肽（ENK）和胆囊收缩素（CCK）。表达这些在点燃的确定阶段激活的PV神经元中的肽将在拟议的实验中分析发展情况。光、电镜免疫细胞化学及原位杂交在这些研究中将使用的方法。的临床意义这些研究也得到了认可，它们将提供新的见解，癫痫发作对脑垂体中枢控制的影响- 肾上腺轴