The impact of repetitive transcranial magnetic stimulation and fluoxetine on the brain lipidome in a rat model of chronic unpredictable stress
The impact of repetitive transcranial magnetic stimulation and fluoxetine on the brain lipidome in a rat model of chronic unpredictable stress
复制标题
重复经颅磁刺激和氟西汀对慢性不可预测应激大鼠模型脑脂质组的影响
DOI：
10.1016/j.pnpbp.2020.109946
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发表时间：
2020
影响因子：
5.6
通讯作者：
Peng Zheng-wu
中科院分区：
文献类型：
--
作者：
Xue Shan-shan;Zhou Cui-hong;Xue Fen;Liu Ling;Cai Yan-hui;Luo Jian-feng;Wang Ying;Tan Qing-rong;Wang Hua-ning;Peng Zheng-wu
重复经颅磁刺激（rTMS）的抗抑郁作用已被广泛研究;越来越多的证据表明，脂质成分的变化可能参与抑郁症的发病机制，并可能是一个有针对性的治疗机制。然而，rTMS对脂质组成的影响以及与氟西汀（Flx）等抗抑郁药相比这些影响之间的差异从未被研究过。使用大鼠慢性不可预测的压力（CUS）模型，我们评估了rTMS和Flx治疗的抗抑郁作用，并使用基于质谱的脂质组学方法评估了海马和前额叶皮质（PFC）中脂质组成的变化。rTMS和Flx治疗均能改善CUS诱导的抑郁样行为。此外，海马中由CUS诱导的脂质组成的变化，特别是甘油磷脂、鞘脂和甘油脂的变化比PFC中观察到的更稳健。CUS导致PFC中含20个碳的脂肪酰基和多不饱和脂肪酰基的水平降低，并且海马和PFC中酰基肉毒碱（AcCa）的水平降低。rTMS治疗对海马中被CUS改变的甘油磷脂和鞘脂的组成的影响高于Flx，而Flx比rTMS在更大程度上减弱了PFC中由NTA诱导的变化。然而，两者都不能将脂肪酰和AcCa恢复到基线水平。总而言之，脑脂质体的调制可能参与rTMS和Flx的抗抑郁作用，这些治疗诱导海马和PFC内脂质组成变化的程度可能解释其差异抗抑郁作用。
The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) has been extensively studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of depression and may be a targeted mechanism for treatment. However, the influence of rTMS on lipid composition and the differences between these effects compared to antidepressants like fluoxetine (Flx) have never been investigated. Using a chronic unpredictable stress (CUS) model in rats, we assessed the antidepressive effects of rTMS and Flx treatments and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. Both rTMS and Flx treatments ameliorated depressive-like behaviors induced by CUS. Moreover, changes in lipid composition, especially glycerophospholipids, sphingolipids, and glycerolipids induced by CUS in the hippocampus were more robust than those observed in the PFC. CUS led to decreased levels of 20 carbon-containing fatty acyls and polyunsaturated fatty acyls in the PFC, and decreased levels of acyl carnitines (AcCa) in both the hippocampus and PFC. Notably, rTMS treatment had higher impact than Flx on composition of glycerophospholipids and sphingolipids in the hippocampus that were altered by CUS, while Flx attenuated CUS-induced changes in the PFC to a greater extent than rTMS. However, neither was able to restore fatty acyls and AcCa to baseline levels. Altogether, modulation of the brain lipidome may be involved in the antidepressant action of rTMS and Flx, and the degree to which these treatments induce changes in lipid composition within the hippocampus and PFC might explain their differential antidepressant effects.