Signal Transduction Mechanisms in Neuroendocrine Neurons

神经内分泌神经元的信号转导机制

• 批准号: 6792844
• 负责人: ARSHAD M. KHAN
• 金额: $ 4.73万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 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/6792844
• 关键词: adrenergic receptor; afferent nerve; biological signal transduction; cAMP response element binding protein; confocal scanning microscopy; corticotropin releasing factor; deoxyglucose; hormone regulation /control mechanism; immunoconjugates; immunocytochemistry; in situ hybridization; laboratory rat; mitogen activated protein kinase; neural information processing; neural transmission; neuroendocrine system; neurotransmitter antagonist; paraventricular nucleus; postdoctoral investigator; stressor

DESCRIPTION (provided by applicant): Corticotropin-releasing hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus (PVH) are critical for adaptive responses to stress, disruptions of which may be linked to stress-related pathologies. The long-term objective of this training proposal is to begin establishing the precise relationships among stimuli that evoke stress responses, the neural pathways conveying that information to the PVH, and the coordinated response of PVH neurons to such information. Specific aims all center around how the hindbrain-originating catecholaminergic (CA) afferents help trigger gene expression in CRH neuroendocrine neurons of the rodent PVH in response to the metabolic stressor, 2-deoxyglucose (2-DG). Proposed training includes: (1) immunohistochemistry and in situ hybridization to track cellular markers of CRH neuronal activity (e.g., MAP kinase, CREB, crh hnRNA), (2) intravenous 2-DG or PVH injection of a retrograde immunotoxin to selectively stimulate or lesion, respectively, the CA afferent system, and (3) PVH microinjections of receptor antagonists or enzyme inhibitors to probe the signaling machinery of CRH neurons. This training will further my career goal of studying cellular signaling using an in vivo approach.

描述（由申请人提供）：下丘脑室旁核（PVH）的含有促肾上腺皮质激素释放激素（CRH）的神经元对于应激的适应性反应至关重要，其破坏可能与应激相关的病理有关。该训练计划的长期目标是开始建立引起应激反应的刺激、将该信息传递到 PVH 的神经通路以及 PVH 神经元对此类信息的协调反应之间的精确关系。具体目标都集中在后脑起源的儿茶酚胺能 (CA) 传入神经如何帮助触发啮齿动物 PVH 的 CRH 神经内分泌神经元中的基因表达，以响应代谢应激源 2-脱氧葡萄糖 (2-DG)。拟议的培训包括：(1) 免疫组织化学和原位杂交，以追踪 CRH 神经元活性的细胞标记（例如 MAP 激酶、CREB、crh hnRNA），(2) 静脉注射 2-DG 或 PVH 逆行免疫毒素，分别选择性刺激或损伤 CA 传入系统，以及 (3) PVH 显微注射 受体拮抗剂或酶抑制剂来探测 CRH 神经元的信号传导机制。这次培训将进一步推进我使用体内方法研究细胞信号传导的职业目标。