Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI to Evaluate the Rapid Antidepressant Effects of Ketamine in the Hippocampus of Rat Depression Model.
Hao Li, Xunrong Luo, Kai Qi, Yijie Lv, Junnan Kan, Changfeng Yang, Xiaoqian Lin, Jin Tao, Wei Zhang, Yan Liu, Kang Rong, Ailing Wang, Zhongde Jiang, Xianglin Li
Journal of Magnetic Resonance Imaging April 2024 DOI: 10.1002/jmri.28921 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized animal model trial Peer reviewed |
|---|---|
| Sample size | 18 |
| Population | Sprague-Dawley rats, including 12 exposed to chronic unpredictable mild stress and 6 unstressed controls |
| Interventions | Ketamine saline |
| Duration | 8 weeks of stress exposure; assessment 30 minutes after injection |
| Measures | GluCEST, 1H MR spectroscopy (MRS), high-performance liquid chromatography (HPLC) |
| Topics | Depression Ketamine Esketamine |
| Keywords | Glucest Hplc Mrs Glutamate |
| Key findings | Chronic stress lowered hippocampal glutamate-related signals, and ketamine injection raised them within 30 minutes toward control levels, whereas saline did not. GluCEST, 1H MRS, and HPLC showed consistent trends, leading the authors to propose GluCEST as a sensitive method for evaluating ketamine's rapid antidepressant effects through glutamate changes. |
Abstract
Ketamine is a quick acting antidepressant drug, and an accurate detection method is lacking. Ketamine's effects in a rat depression model have not previously been well explored using glutamate chemical exchange saturation transfer (GluCEST). To investigate the GluCEST changes of chronic unpredictable mild stress (CUMS) rats after receiving either ketamine or saline injection. Randomized animal model trial. 12 CUMS and 6 Sprague-Dawley rats. Divided into three groups: ketamine (N = 6), saline (N = 6), and control (N = 6). 7.0 T/the sequence is GluCEST and 1 H MR spectroscopy (MRS). The CUMS rats were exposed to different stress factors for 8 weeks. The glutamate concentration in the hippocampus was assessed by the GluCEST,1 H MRS, and the high-performance liquid chromatography (HPLC). The t-test, Mann-Whitney U test, and Pearson's correlation. In depression conditions, GluCEST signals were lower in the bilateral hippocampus than in control group. Thirty minutes after ketamine injection, the GluCEST signals in the bilateral hippocampus were higher compared with the saline group (left: 2.99 ± 0.34 [Control] vs. 2.44 ± 0.20 [Saline] vs. 2.85 ± 0.11 [Ketamine]; right: 2.97 ± 0.28 [Control] vs. 2.49 ± 0.25 [Saline] vs. 2.86 ± 0.19 [Ketamine]). In 1 H MRS, significant changes were only observed in the left hippocampus (2.00 ± 0.16 [Control] vs. 1.81 ± 0.09 [Saline] vs. 2.04 ± 0.14 [Ketamine]). Furthermore, HPLC results showed similar trends to those observed in the GluCEST results (left: 2.32 ± 0.22 [Control] vs. 1.96 ± 0.11 [Saline] vs. 2.18 ± 0.11 [Ketamine]; right: 2.35 ± 0.18 [Control] vs. 1.87 ± 0.16 [Saline] vs. 2.09 ± 0.08 [Ketamine]). GluCEST can sensitively evaluate the ketamine's antidepressant effects by detecting the fast increase in glutamate concentration. 1 TECHNICAL EFFICACY STAGE: 1.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cites 5
- Mechanisms of Ketamine and its Metabolites as Antidepressants Biochemical Pharmacology December 1, 2021
- Ketamine and the Future of Rapid-Acting Antidepressants Annual Review of Clinical Psychology February 9, 2021
- New investigational agents for the treatment of major depressive disorder Expert Opinion on Investigational Drugs August 17, 2022
- Dual action of ketamine confines addiction liability. Nature August 2022
- 7T 1H-MRS in major depressive disorder: a Ketamine Treatment Study. Neuropsychopharmacology August 2018