Repetitive transcranial magnetic stimulation inhibits Sirt1/MAO-A signaling in the prefrontal cortex in a rat model of depression and cortex-derived astrocytes
Repetitive transcranial magnetic stimulation inhibits Sirt1/MAO-A signaling in the prefrontal cortex in a rat model of depression and cortex-derived astrocytes
复制标题
重复经颅磁刺激抑制抑郁症大鼠模型和皮质源性星形胶质细胞前额叶皮质中的 Sirt1/MAO-A 信号传导
DOI：
10.1007/s11010-017-3193-8
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发表时间：
2018
影响因子：
4.3
通讯作者：
Tan Qing rong
中科院分区：
文献类型：
--
作者：
Peng Zheng wu;Xue Fen;Zhou Cui hong;Zhang Rui guo;Wang Ying;Liu Ling;Sang Han fei;Wang Hua ning;Tan Qing rong
重复经颅磁刺激（rTMS）是一种有效的抑郁症单药治疗或难治性抑郁症的连续治疗。然而，不同参数的抗抑郁作用和潜在机制仍不清楚。在这里，我们的目的是评估不同参数的rTMS的效果（1/5/10 Hz，0.84/1.26 T）对抑郁样行为的影响，5-羟色胺（5-HT），5-HIAA（5-羟基吲哚乙酸）和DA和NE水平，以及单胺氧化酶A（MAO-A）活性，沿着sirtuin 1（Sirt 1）和MAO-A在新生大鼠前额叶皮质（PFC）和皮质源性星形胶质细胞中的表达。此外，在每天经颅注射Sirt 1抑制剂EX 527（1 mM）1周后监测抑郁样行为。结果发现，经颅磁刺激（5/10 Hz，0.84/1.26 T）可改善大鼠的抑郁样行为，增加PFC内5-HT、DA和NE水平，降低PFC内5-HIAA水平和Sirt 1、MAO-A表达，降低MAO-A活性。重要的是，rTMS（5/10 Hz，0.84/1.26 T）抑制星形胶质细胞中Sirt 1和MAO-A的表达，并且用短发夹RNA敲低Sirt 1降低星形胶质细胞中MAO-A的表达。这些结果表明，抑制Sirt 1/MAO-A在PFC星形胶质细胞的表达可能有助于不同参数的rTMS的抗抑郁作用的不同，也可能提供了一个新的见解抑郁症的机制。
Repetitive transcranial magnetic stimulation (rTMS) is a useful monotherapy for depression or adjunctive therapy for resistant depression. However, the anti-depressive effects of different parameters and the underlying mechanisms remain unclear. Here, we aimed to assess the effect of rTMS with different parameters (1/5/10 Hz, 0.84/1.26 T) on the depressive-like behaviors, 5-hydroxytryptamine (5-HT), 5-HIAA (5-hydroxyindoleacetic acid) and DA and NE levels, and monoamine oxidase A (MAO-A) activity in chronic unpredictable stress-treated rats, along with the expression of sirtuin 1 (Sirt1) and MAO-A in the prefrontal cortex (PFC) and cortex-derived astrocytes from new-born rats. Moreover, the depressive-like behaviors were monitored following the transcranial injection of the Sirt1 inhibitor EX527 (1 mM) daily for 1 week. We found that rTMS treatment (5/10 Hz, 0.84/1.26 T) ameliorated depressive-like behaviors, increased 5-HT, DA and NE levels, decreased the 5-HIAA level and Sirt1 and MAO-A expression, and reduced MAO-A activity in the PFC. The depressive-like behaviors were also ameliorated after the transcranial injection of EX527. Importantly, rTMS (5/10 Hz, 0.84/1.26 T) inhibited Sirt1 and MAO-A expressions in astrocytes and Sirt1 knockdown with short hairpin RNA decreased MAO-A expression in astrocytes. These results suggest that the inhibition of Sirt1/MAO-A expression in astrocytes in the PFC may contribute to the different anti-depressive effects of rTMS with different parameters, and may also provide a novel insight into the mechanisms underlying major depressive disorder.