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Investigating the metabolic alterations in a depressive-like rat model of chronic forced swim stress: An in vivo proton magnetic resonance spectroscopy study at 7T
Neurochemistry international ( IF 4.2 ) Pub Date : 2018-03-09 , DOI: 10.1016/j.neuint.2018.03.005
Chi-Hyeon Yoo , Song-I Lim , Kyu-Ho Song , Dong-Cheol Woo , Bo-Young Choe

Although recent investigations of major depressive disorder (MDD) have focused on the monoaminergic system, accumulating evidences suggest that alternative pathophysiological models of MDD and treatment options for patients with MDD are needed. Animals subjected to chronic forced swim stress (CFSS) develop behavioral despair. The purpose of this study was to investigate the in vivo effects of CFSS on systems other than the monoamine system in the rat prefrontal cortex (PFC) with 7T and short-echo-time (16.3 ms) proton magnetic resonance spectroscopy (1H MRS). Ten male Wistar rats underwent 14 days of CFSS, and in vivo 1H MRS and forced swim tests were performed before and after CFSS. Point-resolved spectroscopy was used to quantify metabolite levels in the rat PFC. To investigate spectral overlap in glutamate and glutamine, spectral analyses in the spectra obtained in the in vivo 1H MRS, parametrically matched spectral simulation, and in vitro experiments were performed. The results of the spectral analyses showed that the glutamate/glutamine spectral overlap was not critical, which suggested that in vivo 1H MRS can be used to reliably assess the glutamate system. The rats showed significantly increased immobility times and decreased climbing times in the FST after CFSS, which suggested that the rats developed behavioral despair. The pre-CFSS and post-CFSS glutamate and glutamine levels did not significantly differ (p > 0.050). The levels of myo-inositol, total choline, and N-acetylaspartate, myo-inositol/creatine, and total choline/creatine increased significantly (p < 0.050). Similar findings have been reported in patients with MDD. Taken together, these results suggest that the CFSS-induced metabolic alterations were similar to those found in patients and that high-field and short-echo-time in vivo 1H MRS can be used to investigate depression-induced metabolic alterations. Such investigations might provide alternative insights into the nonmonoaminergic pathophysiology and treatment of depression.



中文翻译:

研究慢性强迫游泳应激的抑郁样大鼠模型中的代谢变化:7T体内质子磁共振波谱研究

尽管最近对重性抑郁症(MDD)的研究集中在单胺能系统上,但越来越多的证据表明,需要MDD的替代病理生理模型和MDD患者的治疗选择。遭受慢性强迫游泳压力(CFSS)的动物会表现出绝望的行为。这项研究的目的是通过7T和短回波时间(16.3 ms)质子磁共振波谱(1 H MRS)研究CFSS对大鼠前额叶皮层(PFC)中单胺系统以外的系统的体内影响。。10只雄性Wistar大鼠接受CFSS 14天,并在体内1 在CFSS之前和之后进行了H MRS和强制游泳测试。点分辨光谱法用于定量大鼠PFC中的代谢物水平。为了研究谷氨酸和谷氨酰胺中的光谱重叠,对体内 1 H MRS获得的光谱进行光谱分析,参数匹配的光谱模拟和体外实验。光谱分析的结果表明,谷氨酸/谷氨酰胺光谱重叠不是关键的,这表明体内 1H MRS可用于可靠地评估谷氨酸系统。在CFSS后,FST大鼠的固定时间显着增加,攀爬时间减少,这表明大鼠表现出了绝望的行为。CFSS之前和之后的CFSS谷氨酸和谷氨酰胺水平没有显着差异(p  > 0.050)。肌醇,总胆碱和N-乙酰天门冬氨酸,肌醇/肌酸和总胆碱/肌酸的水平显着增加(p  <0.050)。在MDD患者中也报道了类似的发现。综上所述,这些结果表明CFSS诱导的代谢改变与患者中发现的相似,并且体内 高场和短回波时间1H MRS可用于研究抑郁症引起的代谢改变。这样的研究可能会为非单胺能的病理生理学和抑郁症的治疗提供另类的见解。

更新日期:2018-03-09
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