Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Neurochem Int. 2018 Jun;116:22-29. doi: 10.1016/j.neuint.2018.03.005. Epub 2018 Mar 9.
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 (H MRS). Ten male Wistar rats underwent 14 days of CFSS, and in vivoH 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 vivoH 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 vivoH 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 vivoH MRS can be used to investigate depression-induced metabolic alterations. Such investigations might provide alternative insights into the nonmonoaminergic pathophysiology and treatment of depression.
尽管最近对重度抑郁症 (MDD) 的研究集中在单胺能系统上，但越来越多的证据表明，需要对 MDD 的替代病理生理学模型和 MDD 患者的治疗选择进行研究。经过慢性强迫游泳应激 (CFSS) 处理的动物会出现行为绝望。本研究的目的是使用 7T 和短回波时间 (16.3 ms) 质子磁共振波谱 (H MRS) 研究 CFSS 对大鼠前额叶皮质 (PFC) 中单胺能系统以外的其他系统的体内影响。10 只雄性 Wistar 大鼠接受了 14 天的 CFSS，在 CFSS 前后进行了体内 H MRS 和强迫游泳测试。点分辨波谱法用于定量大鼠 PFC 中的代谢物水平。为了研究谷氨酸和谷氨酰胺的光谱重叠，对体内 H MRS 获得的光谱中的光谱分析、参数匹配的光谱模拟和体外实验进行了研究。光谱分析的结果表明，谷氨酸/谷氨酰胺光谱重叠并不关键，这表明体内 H MRS 可用于可靠地评估谷氨酸系统。CFSS 后，大鼠在 FST 中的不动时间明显增加，攀爬时间明显减少，这表明大鼠出现了行为绝望。CFSS 前后谷氨酸和谷氨酰胺水平无显著差异 (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/肌酸水平显著增加 (p < 0.050)。在 MDD 患者中也有类似的发现。总之，这些结果表明，CFSS 诱导的代谢改变与患者中发现的改变相似，高场和短回波时间体内 H MRS 可用于研究抑郁诱导的代谢改变。这种研究可能为非单胺能病理生理学和抑郁症治疗提供替代见解。
