Role of nuclear calcium signaling in the control of activity-dependent modulation of BDNF gene expression in hippocampal neurons

核钙信号传导在海马神经元 BDNF 基因表达活性依赖性调节中的作用

• 批准号: 5426359
• 负责人: Professor Dr. Hilmar Bading
• 金额: --
• 依托单位: Interdisziplinäres Zentrum für Neurowissenschaften (IZN)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5426359?language=en
• 关键词: Role; nuclear; calcium; signaling; control

The neurotrophin brain-derived neurotrophic factor (BDNF) has many roles in the developing nervous system and is also a key player in neuronal plasticity and learning-related events. BDNF can induce and help to maintain long term potentiation (LTP), a persistent increase in synaptic efficacy that is thought to underlie learning and memory. BDNF harbors the potential to be used in therapies to improve deficits in cognitive functions associated with, for example, neurodegenerative diseases. An attractive alternative to the treatment with exogenous BDNF is the modulation of expression of the endogenous BDNF. BDNF gene expression is not constant but subject to regulation by electrical activity and the activation of intracellular calcium signaling pathways. An important regulator of BDNF transcription is the N-Methyl-D-Aspartate (NMDA) receptor; this calciumpermeable glutamate receptor can, depending on the localization of the receptor activated (synaptic or extrasynaptic), increase or shut-down BDNF transcription. Several transcription factors, most notably the CREB/CBP complex, regulate BDNF transcription. CREB/CBP-dependent transcription requires increases in the nuclear calcium concentration, raising the possibility that nuclear calcium transients regulate BDNF expression. Aim of this project is to investigate the role of nuclear calcium in BDNF gene expression. We plan to develop technologies to generate or interfere with nuclear calcium signaling. New mechanistic insight into the control of BDNF gene transcription may lead to novel strategies to modulate BDNF expression in vivo.

神经营养蛋白脑源性神经营养因子 (BDNF) 在神经系统发育中发挥多种作用，也是神经元可塑性和学习相关事件的关键参与者。 BDNF 可以诱导并帮助维持长期增强 (LTP)，即突触功效的持续增强，被认为是学习和记忆的基础。 BDNF 具有用于改善与神经退行性疾病等相关的认知功能缺陷的疗法的潜力。外源性 BDNF 治疗的一个有吸引力的替代方案是调节内源性 BDNF 的表达。 BDNF 基因表达不是恒定的，而是受到电活动和细胞内钙信号通路激活的调节。 BDNF 转录的一个重要调节因子是 N-甲基-D-天冬氨酸 (NMDA) 受体；这种钙渗透性谷氨酸受体可以根据激活的受体的定位（突触或突触外）增加或关闭 BDNF 转录。多种转录因子，尤其是 CREB/CBP 复合物，调节 BDNF 转录。 CREB/CBP依赖性转录需要增加核钙浓度，这增加了核钙瞬变调节BDNF表达的可能性。该项目的目的是研究核钙在 BDNF 基因表达中的作用。我们计划开发产生或干扰核钙信号传导的技术。对 BDNF 基因转录控制的新机制认识可能会导致体内调节 BDNF 表达的新策略。