Metabolic Demand Stimulates CREB Signaling in the Limbic Cortex: Implication for the Induction of Hippocampal Synaptic Plasticity by Intrinsic Stimulus for Survival.
Metabolic Demand Stimulates CREB Signaling in the Limbic Cortex: Implication for the Induction of Hippocampal Synaptic Plasticity by Intrinsic Stimulus for Survival.
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DOI：
10.3389/neuro.06.005.2009
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发表时间：
2009
影响因子：
3
通讯作者：
Isokawa M
中科院分区：
文献类型：
--
作者：
Estrada NM;Isokawa M
通过禁食限制热量被认为有助于促进突触可塑性和促进上下文学习。然而，细胞和分子机制的基础上禁食记忆巩固的影响还没有完全理解。我们推测，禁食诱导的突触可塑性增强是由CREB（cAMP反应元件结合蛋白）介导的信号传导增加介导的，CREB是一种重要的核蛋白，也是参与海马记忆巩固的转录因子。在禁食18 h的大鼠体内模型中，使用抗磷酸化CREB（Ser 133）在心脏灌注和冷冻切片的大鼠脑标本中检测磷酸化CREB（pCREB）的表达。当与对照动物相比，海马表现出高达两倍的增加，在禁食动物的pCREB表达。梨状皮质、内嗅皮质和皮质-杏仁核过渡区对pCREB的免疫反应也显著增加。相比之下，杏仁核没有表现出任何变化的pCREB表达的幅度响应于禁食。弓状核在内侧下丘脑，这是以前报道上调CREB磷酸化在禁食长达48小时，也是强烈的免疫反应，并提供了一个阳性对照在本研究中。我们的研究结果表明，代谢需求不仅刺激下丘脑中的cAMP依赖性信号级联，而且还通过激活CREB信号机制向包括海马在内的各个边缘脑区域发出信号。海马体是学习和记忆的主要大脑结构。它接受直接来自穹窿的下丘脑和弓形投射。海马体也位于中央，通过建立相互突触连接与其他边缘皮层进行功能性相互作用。我们认为，海马神经元和周围的边缘皮质密切参与代谢依赖的可塑性，这可能是必要的和必要的成功实现适应性食欲行为。
Caloric restriction by fasting has been implicated to facilitate synaptic plasticity and promote contextual learning. However, cellular and molecular mechanisms underlying the effect of fasting on memory consolidation are not completely understood. We hypothesized that fasting-induced enhancement of synaptic plasticity was mediated by the increased signaling mediated by CREB (cAMP response element binding protein), an important nuclear protein and the transcription factor that is involved in the consolidation of memories in the hippocampus. In the in vivo rat model of 18 h fasting, the expression of phosphorylated CREB (pCREB) was examined using anti-phospho-CREB (Ser133) in cardially-perfused and cryo-sectioned rat brain specimens. When compared with control animals, the hippocampus exhibited up to a twofold of increase in pCREB expression in fasted animals. The piriform cortex, the entorhinal cortex, and the cortico-amygdala transitional zone also significantly increased immunoreactivities to pCREB. In contrast, the amygdala did not show any change in the magnitude of pCREB expression in response to fasting. The arcuate nucleus in the medial hypothalamus, which was previously reported to up-regulate CREB phosphorylation during fasting of up to 48 h, was also strongly immunoreactive and provided a positive control in the present study. Our findings demonstrate a metabolic demand not only stimulates cAMP-dependent signaling cascades in the hypothalamus, but also signals to various limbic brain regions including the hippocampus by activating the CREB signaling mechanism. The hippocampus is a primary brain structure for learning and memory. It receives hypothalamic and arcuate projections directly from the fornix. The hippocampus is also situated centrally for functional interactions with other limbic cortexes by establishing reciprocal synaptic connections. We suggest that hippocampal neurons and those in the surrounding limbic cortexes are intimately involved in the metabolism-dependent plasticity, which may be essential and necessary for successful achievement of adaptive appetitive behavior.