Instant and Lasting Down-Regulation of NR1 Expression in the Hippocampus is Associated Temporally with Antidepressant Activity After Acute Yueju
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- 作者：Baomei Xia ; Hailou Zhang ; Wenda Xue ; Weiwei Tao…
- 刊名：Cellular and Molecular Neurobiology
- 出版年：2016
- 出版时间：October 2016
- 年：2016
- 卷：36
- 期：7
- 页码：1189-1196
- 全文大小：771 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Neurosciences
Animal Anatomy, Morphology and Histology - 出版者：Springer Netherlands
- ISSN：1573-6830
- 卷排序：36
文摘
Accumulating evidence indicated that N-methyl-d-aspartate (NMDA) receptors are involved in the pathophysiology of depression and implicated in therapeutic targets. NMDA antagonists, such as ketamine, displayed fast-onset and long-lasting antidepressant activity in preclinical and clinical studies. Previous studies showed that Yueju pill exerts antidepressant effects similar to ketamine. Here, we focused on investigating the association of acute and lasting antidepressant responses of Yueju with time course changes of NMDA receptor subunits NR1, NR2A, and NR2B expressions in the hippocampus, a key region regulating depression response. As a result, Yueju reduced immobility time in the forced swimming test from 30 min to 5 days post a single administration. Yueju acutely decreased NR1 and NR2B protein expression in the hippocampus, with NR2A expression unaltered. NR1 expression remained down-regulated 5 days post Yueju administration, whereas NR2B returned to normal level in 24 h. Yueju and ketamine similarly ameliorated the depression-like symptoms at least for 72 h in learned helplessness test. They both reversed the up-regulated expression of NR1 in the learned helpless mice 1 or 3 days post administration. Different from ketamine, the antidepressant effects of Yueju were not influenced by blockade of amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor. These findings served as preclinical evidence that Yueju may confer acute and long-lasting antidepressant effects by favorably modulating NMDA function in the hippocampus.KeywordsNMDA receptorNR1GluA1Yueju pillKetamineLearned helplessness