Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Brain Res. 2010 Aug 12;1348:105-13. doi: 10.1016/j.brainres.2010.05.097. Epub 2010 Jun 10.
The forced swim test (FST) is a behavioral paradigm that is predicative of antidepressant activity in rodents. The objective of this study was to examine the effects of desipramine (DMI) pretreatment on behavioral and regional neurochemical responses in the left dorsolateral prefrontal cortex (DLPFC) and hippocampus of mice exposed to the FST using proton magnetic resonance spectroscopy ((1)H-MRS). An ultra short echo stimulated echo acquisition (STEAM) localization sequence (TR/TM/TE=5000/20/2.2ms) was used to measure in vivo proton spectra from the left DLPFC (voxel volume: 7microl) and hippocampus (6microl) of C57BL/6 mice at 9.4T and acquired proton spectra post-processed offline with LCModel. The FST induced significant increase of glutamate (Glu) and myo-inositol (mIns) concentrations in the left DLPFC and hippocampus, respectively. In addition, creatine+phosphocreatine (Cr+PCr) concentrations in the left DLPFC were significantly decreased as compared to control. The metabolic alterations induced by the FST were reverted to level similar to control by acute DMI administration. Our results suggest that glutamatergic activity and glial cell dysfunction may contribute to the pathophysiological mechanisms underlying depression and that modulation of synaptic neurotransmitter concentrations represents a potential target for antidepressant drug development.
强迫游泳测试（FST）是一种预测啮齿动物抗抑郁活性的行为范式。本研究的目的是使用质子磁共振波谱（1H-MRS）检查去甲丙咪嗪（DMI）预处理对暴露于 FST 的小鼠左背外侧前额叶皮层（DLPFC）和海马区的行为和区域神经化学反应的影响。采用超短回波激发回波采集（STEAM）定位序列（TR/TM/TE=5000/20/2.2ms），从 C57BL/6 小鼠的左 DLPFC（体素体积：7microl）和海马区（6microl）测量 9.4T 时的体内质子谱，并使用 LCModel 离线处理后处理获得的质子谱。FST 导致左 DLPFC 和海马区的谷氨酸（Glu）和肌醇（mIns）浓度分别显著增加。此外，与对照组相比，左 DLPFC 中的肌酸+磷酸肌酸（Cr+PCr）浓度显著降低。FST 引起的代谢改变通过急性 DMI 给药恢复到类似对照的水平。我们的结果表明，谷氨酸能活动和神经胶质细胞功能障碍可能有助于抑郁的病理生理机制，而突触神经递质浓度的调节可能是抗抑郁药物开发的潜在靶点。
