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Early Life Stress Increases Brain Glutamate and Induces Neurobehavioral Manifestations in Rats
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-11-12 , DOI: 10.1021/acschemneuro.0c00454
Jitian Guan 1, 2, 3 , Yan Ding 4 , Yunjie Rong 1 , Yiqun Geng 2, 3, 5 , Lingfeng Lai 1 , Dan Qi 2, 3 , Yanyan Tang 1 , Lin Yang 1 , Juntao Li 6 , Teng Zhou 7 , Erxi Wu 2, 3, 8, 9, 10 , Renhua Wu 1
Affiliation  

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 1H 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 1H 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 (p < 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 1H 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 1H MRS-identified associations between Glu levels and ELS may guide future clinical studies.

中文翻译:

早年生活压力增加大脑谷氨酸并诱导大鼠神经行为表现

早期生活压力 (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 1 H MRS) 检测大鼠模型中的代谢 Glu,以研究母体剥夺 (MD) 诱导的 ELS。通过定期与母亲和同龄人分离,在 Sprague-Dawley 大鼠中建立了 MD。通过 7T 1检测海马体积和 Glu 代谢的变化通过开阔场地、蔗糖偏好和 Morris 水迷宫测试测试抑郁样行为后的 H MRS。成年 MD 后代表现出抑郁样行为。与对照组相比,MD 组表现出中枢活动时间与总时间的比率降低以及蔗糖消耗减少 ( p < 0.05)。在 Morris 水迷宫测试中,MD 大鼠在最初放置平台的第四象限花费的时间较少。根据 7T 1H MRS,与对照组海马相比,MD大鼠海马Glu和谷氨酸+谷氨酰胺(Glu+Gln)水平升高,但前额叶Gln、γ-氨基丁酸(GABA)和谷氨酸+谷氨酰胺(Glu+Gln) MD大鼠皮质呈下降趋势。与 ELS 相关的抑郁样行为和认知缺陷可能会引起前额叶皮层和海马体中 Glu 代谢的区域特异性变化。Glu 水平和 ELS 之间新颖的、非侵入性的 7T 1 H MRS 鉴定关联可能指导未来的临床研究。
更新日期:2020-12-16
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