Ingested D-Aspartate Facilitates the Functional Connectivity and Modifies Dendritic Spine Morphology in Rat Hippocampus
Ingested D-Aspartate Facilitates the Functional Connectivity and Modifies Dendritic Spine Morphology in Rat Hippocampus
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DOI：
10.1093/cercor/bhy120
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发表时间：
2019-06-01
期刊：
影响因子：
3.7
通讯作者：
Tsurugizawa, Tomokazu
中科院分区：
文献类型：
--
作者：
Kitamura, Akihiko;Hojo, Yasushi;Tsurugizawa, Tomokazu
d -天冬氨酸（D-Asp）是l -天冬氨酸的立体异构体，在啮齿类动物的记忆功能中起作用。然而，D-Asp的作用机制尚不完全清楚。在本研究中，我们假设摄取的D-Asp通过血液循环直接到达海马组织，并通过海马CA1神经元的脊髓发生改变海马与其他区域的功能连通性。采用大鼠急性海马切片研究D-Asp对脊髓发生的影响。施M D-Asp 21和100亩后CA1棘密度均有增加。非基因组脊柱增加途径涉及LIM激酶。与急性切片研究平行，在清醒大鼠灌胃5mm D-Asp后，使用功能MRI研究脑激活。D-Asp灌胃15 min后，大鼠血清和海马中D-Asp浓度显著升高。清醒大鼠fMRI功能连接显示，在D-Asp开始给药10-20分钟后，海马和其他区域（包括体感觉皮层、纹状体和伏隔核）的慢频同步增加。这些结果表明，摄入的D-Asp通过血液循环到达大脑，并通过调节脊柱调节海马神经网络。
D-Aspartate (D-Asp), the stereoisomer of L-aspartate, has a role in memory function in rodents. However, the mechanism of the effect of D-Asp has not been fully understood. In this study, we hypothesized that ingested D-Asp directly reaches the hippocampal tissues via the blood circulation and modifies the functional connectivity between hippocampus and other regions through spinogenesis in hippocampal CA1 neurons. The spinogenesis induced by the application of D-Asp was investigated using rat acute hippocampal slices. The density of CA1 spines was increased following 21 and 100 mu M D-Asp application. The nongenomic spine increase pathway involved LIM kinase. In parallel to the acute slice study, brain activation was investigated in awake rats using functional MRI following the intragastric administration of 5 mM D-Asp. Furthermore, the concentration of D-Asp in the blood serum and hippocampus was significantly increased 15 min after intragastric administration of D-Asp. A functional connectivity by awake rat fMRI demonstrated increased slow-frequency synchronization in the hippocampus and other regions, including the somatosensory cortex, striatum, and the nucleus accumbens, 10-20 min after the start of D-Asp administration. These results suggest that ingested D-Asp reaches the brain through the blood circulation and modulates hippocampal neural networks through the modulation of spines.