Guan Jitian, Ding Yan, Rong Yunjie, Geng Yiqun, Lai Lingfeng, Qi Dan, Tang Yanyan, Yang Lin, Li Juntao, Zhou Teng, Wu Erxi, Wu Renhua
Department of Radiology, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas 76502, United States.
ACS Chem Neurosci. 2020 Dec 16;11(24):4169-4178. doi: 10.1021/acschemneuro.0c00454. Epub 2020 Nov 12.
Early life stress (ELS) is associated with an increased risk of developing depression and anxiety disorders. Disturbances of the neurobiological glutamatergic system are implicated in depression; however, the long-term effects of ELS on glutamate (Glu) metabolites remain unclear. Our study used 7T proton magnetic resonance spectroscopy (7T H MRS) to detect metabolic Glu in a rat model to investigate maternal deprivation (MD)-induced ELS. MD was established in Sprague-Dawley rats by periodic separation from mothers and peers. Changes in the hippocampal volume and Glu metabolism were detected by 7T H MRS after testing for depression-like behavior via open field, sucrose preference, and Morris water maze tests. Adult MD offspring exhibited depression-like behavior. Compared to the control, the MD group exhibited reduced ratio of central activity time to total time and decreased sucrose consumption ( < 0.05). MD rats spent less time in the fourth quadrant, where the platform was originally placed, in the Morris water maze test. According to 7T H MRS, hippocampus of MD rats had elevated Glu and glutamate + glutamine (Glu+Gln) levels compared with the control group hippocampi, but Gln, γ-aminobutyric acid (GABA), and glutamate + glutamine (Glu+Gln) in the prefrontal cortex of MD rats showed a downward trend. Depression-like behavior and cognition deficits related to ELS may induce region-specific changes in Glu metabolism in the prefrontal cortex and hippocampus. The novel, noninvasive 7T H MRS-identified associations between Glu levels and ELS may guide future clinical studies.
早年生活应激（ELS）与患抑郁症和焦虑症的风险增加有关。神经生物学谷氨酸能系统的紊乱与抑郁症有关；然而，ELS对谷氨酸（Glu）代谢产物的长期影响仍不清楚。我们的研究使用7T质子磁共振波谱（7T H MRS）在大鼠模型中检测代谢性Glu，以研究母婴分离（MD）诱导的ELS。通过定期与母亲和同伴分离，在Sprague-Dawley大鼠中建立MD模型。通过旷场试验、蔗糖偏好试验和莫里斯水迷宫试验检测抑郁样行为后，用7T H MRS检测海马体积和Glu代谢的变化。成年MD后代表现出抑郁样行为。与对照组相比，MD组的中央活动时间与总时间之比降低，蔗糖消耗量减少（<0.05）。在莫里斯水迷宫试验中，MD大鼠在平台最初放置的第四象限停留的时间较少。根据7T H MRS，与对照组海马相比，MD大鼠海马中的Glu和谷氨酸+谷氨酰胺（Glu+Gln）水平升高，但MD大鼠前额叶皮质中的谷氨酰胺（Gln）、γ-氨基丁酸（GABA）和谷氨酸+谷氨酰胺（Glu+Gln）呈下降趋势。与ELS相关的抑郁样行为和认知缺陷可能会诱导前额叶皮质和海马中Glu代谢的区域特异性变化。7T H MRS新发现的Glu水平与ELS之间的非侵入性关联可能会为未来的临床研究提供指导。
