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7.0 T MR GluCEST imaging application value in evaluating therapeutic efficacy of model rats with depression
ZHANG Jie  NIE Taiming  ZHENG Lei  HUANG Delong  XU Yangyang  QI Kai  ZHANG Shuping  JIANG Xingyue 

Cite this article as: ZHANG J, NIE T M, ZHENG L, et al. 7.0 T MR GluCEST imaging application value in evaluating therapeutic efficacy of model rats with depression[J]. Chin J Magn Reson Imaging, 2024, 15(12): 53-59. DOI:10.12015/issn.1674-8034.2024.12.008.


[Abstract] Objective To investigate the application value of 7.0 T magnetic resonance glutamate chemical exchange saturation transfer (GluCEST) imaging for quantitatively evaluating the changes in hippocampal glutamate concentration before and after treatment in rats modeled with depression.Materials and Methods Thirty-six male SD rats were subjected to depression-like behavior induced by chronic unpredictable mild stress (CUMS) model and randomly divided into three groups: normal control group, CUMS group, and fluoxetine administration group (CUMS-fluoxetine), twelve rats per group. Sugar water preference test (SPT), forced swimming test (FST) and open field test (OPT) were used to evaluate the depression-like behavior of rats. T2WI and GluCEST sequences were acquired using a 7.0 T small animal MRI scanner, and the relative concentration values of glutamate in the hippocampus were determined using Matlab software. CUMS group and normal control group, CUMS-fluoxetine group and CUMS group were respectively compared, the bilateral hippocampal regions of rats in each of the three groups were compared within the groups,the therapeutic effect of the administered groups was assessed.Results (1) Behavioral results showed that rats in the CUMS group had decreased sugar-water preference, prolonged immobility time in the forced swim test and decreased exercise distance in the open field test, while the CUMS-fluoxetine group had increased sugar-water preference, decreased immobility time in the forced swim test and increased exercise distance in the open field test. (2) The results of GluCEST assay values showed that the glutamate concentration in the bilateral hippocampal region was significantly higher in the CUMS group compared with the normal control group (left P<0.001, right P=0.014), the glutamate concentration in the bilateral hippocampal region in the CUMS-fluoxetine group was significantly reduced compared with that in the CUMS group (left P=0.002, right P=0.025), within-group comparisons of the bilateral hippocampal regions of the three groups of rats respectively, the differences in glutamate concentrations between the left and right hippocampal regions were not statistically significant (P>0.05), the hippocampal region of the CUMS-fluoxetine group had glutamate concentrations close to those of the normal control group.Conclusions 7.0 T MR GluCEST imaging can noninvasively and quantitatively reflect the changes of glutamate concentration in bilateral hippocampal region before and after treatment in depression model rats, which can provide a theoretical basis for clinical assessment of the efficacy of depression.
[Keywords] depression；chronic unpredictable mild stress；hippocampus；glutamate chemical exchange saturation shift imaging；magnetic resonance imaging

ZHANG Jie1   NIE Taiming1   ZHENG Lei2   HUANG Delong2   XU Yangyang3   QI Kai4   ZHANG Shuping5   JIANG Xingyue1*  

1 Department of Radiology, Binzhou Medical University Hospital, Binzhou256603, China

2 Department of Imaging, Yantaishan Hospital, Yantai264003, China

3 Department of Pharmacy, Binzhou Medical University Hospital, Binzhou256603, China

4 School of Medical Imaging, Binzhou Medical University, Yantai264003, China

5 School of Pharmacy, Binzhou Medical University, Yantai264003, China

Corresponding author: JIANG X Y, E-mail: xyjiang188@sina.com

Conflicts of interest   None.

Received  2024-03-27
Accepted  2024-10-21
DOI: 10.12015/issn.1674-8034.2024.12.008
Cite this article as: ZHANG J, NIE T M, ZHENG L, et al. 7.0 T MR GluCEST imaging application value in evaluating therapeutic efficacy of model rats with depression[J]. Chin J Magn Reson Imaging, 2024, 15(12): 53-59. DOI:10.12015/issn.1674-8034.2024.12.008.

[1]
CUI L L, LI S, WANG S M, et al. Major depressive disorder: hypothesis, mechanism, prevention and treatment[J/OL]. Signal Transduct Target Ther, 2024, 9(1): 30 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/38331979/. DOI: 10.1038/s41392-024-01738-y.
[2]
ÜNAL G Ö, ERKıLıNÇ G, ÖZTÜRK K H, et al. The beneficial effects of vortioxetine on BDNF, CREB, S100B, β amyloid, and glutamate NR2b receptors in chronic unpredictable mild stress model of depression[J]. Psychopharmacology, 2023, 240(12): 2499-2513. DOI: 10.1007/s00213-023-06445-0.
[3]
LI Y F. A hypothesis of monoamine (5-HT) - Glutamate/GABA long neural circuit: aiming for fast-onset antidepressant discovery[J/OL]. Pharmacol Ther, 2020, 208: 107494 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/31991195/. DOI: 10.1016/j.pharmthera.2020.107494.
[4]
BERGER T, LEE H, YOUNG A H, et al. Adult hippocampal neurogenesis in major depressive disorder and Alzheimer's disease[J]. Trends Mol Med, 2020, 26(9): 803-818. DOI: 10.1016/j.molmed.2020.03.010.
[5]
XIU J B, LI J Y, LIU Z Y, et al. Elevated BICD2 DNA methylation in blood of major depressive disorder patients and reduction of depressive-like behaviors in hippocampal Bicd2-knockdown mice[J/OL]. Proc Natl Acad Sci USA, 2022, 119(30): e2201967119 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/35858435/. DOI: 10.1073/pnas.2201967119.
[6]
QIAN H, SHU C, XIAO L, et al. Histamine and histamine receptors: roles in major depressive disorder[J/OL]. Front Psychiatry, 2022, 13: 825591 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/36213905/. DOI: 10.3389/fpsyt.2022.825591.
[7]
DREVETS W C, WITTENBERG G M, BULLMORE E T, et al. Immune targets for therapeutic development in depression: towards precision medicine[J]. Nat Rev Drug Discov, 2022, 21(3): 224-244. DOI: 10.1038/s41573-021-00368-1.
[8]
LI Y, SU P, CHEN Y X, et al. The Eph receptor A4 plays a role in demyelination and depression-related behavior[J/OL]. J Clin Investig, 2022, 132(10) [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/35575094/. DOI: 10.1172/jci161559.
[9]
QIAO H, LI M X, XU C, et al. Dendritic spines in depression: what we learned from animal models[J/OL]. Neural Plast, 2016, 2016: 8056370 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/26881133/. DOI: 10.1155/2016/8056370.
[10]
Chinese Society of Psychiatry, Chinese Academy of Depressive Disorders. Expert consensus on assessment and intervention of cognitive symptoms in major depressive disorder[J]. Chin J Psychiatry, 2020, 53(5): 369-376. DOI: 10.3760/cma.j.cn113661-20200410-00177.
[11]
LI H, JIANG Z D, LI X L. Research progress of multimodal MRI in evaluating the rapid antidepressant effect of ketamine[J]. Chin J Magn Reson Imag, 2023, 14(4): 115-119. DOI: 10.12015/issn.1674-8034.2023.04.020.
[12]
ZENG Z, DONG Y Y, ZOU L X, et al. GluCEST imaging and structural alterations of the bilateral hippocampus in first-episode and early-onset major depression disorder[J]. J Magn Reson Imaging, 2023, 58(5): 1431-1440. DOI: 10.1002/jmri.28651.
[13]
KIM J, KIM T E, LEE S H, et al. The role of glutamate underlying treatment-resistant depression[J]. Clin Psychopharmacol Neurosci, 2023, 21(3): 429-446. DOI: 10.9758/cpn.22.1034.
[14]
RITTER C, BUCHMANN A, MÜLLER S T, et al. Evaluation of prefrontal γ-aminobutyric acid and glutamate levels in individuals with major depressive disorder using proton magnetic resonance spectroscopy[J]. JAMA Psychiatry, 2022, 79(12): 1209-1216. DOI: 10.1001/jamapsychiatry.2022.3384.
[15]
REN Q F, WAN B, LUO X R, et al. Glutamate alterations in the premature infant brain during different gestational ages with glutamate chemical exchange saturation transfer imaging: a pilot study[J]. Eur Radiol, 2023, 33(6): 4214-4222. DOI: 10.1007/s00330-022-09374-2.
[16]
LI G D, LIU Y, LI H, et al. Application value of glutamate chemical exchange saturation transfer imaging in radiation-induced brain injury rat[J]. Chin J Magn Reson Imag, 2023, 14(12): 85-90, 97. DOI: 10.12015/issn.1674-8034.2023.12.014.
[17]
CEMBER A T J, NANGA R P R, REDDY R. Glutamate-weighted CEST (gluCEST) imaging for mapping neurometabolism: an update on the state of the art and emerging findings from in vivo applications[J/OL]. NMR Biomed, 2023, 36(6): e4780 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/35642353/. DOI: 10.1002/nbm.4780.
[18]
LUO X R, REN Q F, LUO M F, et al. Glutamate chemical exchange saturation transfer imaging and functional alterations of hippocampus in rat depression model: a pilot study[J]. J Magn Reson Imaging, 2021, 54(6): 1967-1976. DOI: 10.1002/jmri.27850.
[19]
LI H, LUO X R, QI K, et al. Glutamate chemical exchange saturation transfer (GluCEST) MRI to evaluate the rapid antidepressant effects of ketamine in the hippocampus of rat depression model[J]. J Magn Reson Imaging, 2024, 59(4): 1373-1381. DOI: 10.1002/jmri.28921.
[20]
DI M Q, HU L L, GUI S H, et al. Clinical trial of fluoxetine hydrochloride dispersible tablets combined with alprazolam tablets in the treatment of patients with cerebral infarction at recovery stage[J]. Chin J Clin Pharmacol, 2021, 37(13): 1631-1633, 1637. DOI: 10.13699/j.cnki.1001-6821.2021.13.002.
[21]
YU Q Y, YANG Y, LIU M L, et al. Research Progress in Experimental Animal Depression Model[J]. Medical Recapitulate, 2021, 027(008): 1574-1579, 1584. DOI: 10.3969/j.issn.1006-2084.2021.08.021.
[22]
HUANG Y N, HE X H, ZHENG X X, et al. Research progress in chronic unpredictable mild stress depression model[J]. Med Recapitul, 2020, 26(1): 54-58. DOI: 10.3969/j.issn.1006-2084.2020.01.011.
[23]
CHANG X, SHEN W, WU Y, et al. Establishment and evaluation of chronic social frustration stress model in mice[J]. Military Medical Sciences, 2019, 43(12): 947-953. DOI: 10.7644/j.issn.1674-9960.2019.12.011.
[24]
ANTONIUK S, BIJATA M, PONIMASKIN E, et al. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability[J/OL]. Neurosci Biobehav Rev, 2019, 99: 101-116 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/30529362/. DOI: 10.1016/j.neubiorev.2018.12.002.
[25]
XU Y, ZHUANG Z R, ZHENG H Y, et al. Glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging of rat brain with acute carbon monoxide poisoning[J/OL]. Front Neurol, 2022, 13: 865970 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/35665050/. DOI: 10.3389/fneur.2022.865970.
[26]
NEAL A, MOFFAT B A, STEIN J M, et al. Glutamate weighted imaging contrast in gliomas with 7 Tesla magnetic resonance imaging[J/OL]. Neuroimage Clin, 2019, 22: 101694 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/30822716/. DOI: 10.1016/j.nicl.2019.101694.
[27]
LUCAS A, NANGA R P R, HADAR P, et al. Mapping hippocampal glutamate in mesial temporal lobe epilepsy with glutamate weighted CEST (GluCEST) imaging[J]. Hum Brain Mapp, 2023, 44(2): 549-558. DOI: 10.1002/hbm.26083.
[28]
WANG K, WEN Q Q, WU D C, et al. Lateralization of temporal lobe epileptic foci with automated chemical exchange saturation transfer measurements at 3 Tesla[J/OL]. EBioMedicine, 2023, 89: 104460 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/36773347/. DOI: 10.1016/j.ebiom.2023.104460.
[29]
ZHOU X M, LIU C Y, LIU Y Y, et al. Xiaoyaosan alleviates hippocampal glutamate-induced toxicity in the CUMS rats via NR2B and PI3K/akt signaling pathway[J/OL]. Front Pharmacol, 2021, 12: 586788 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/33912031/. DOI: 10.3389/fphar.2021.586788.
[30]
LUO D, MA R, WU Y N, et al. Mechanism underlying acupuncture-ameliorated depressive behaviors by enhancing glial glutamate transporter in chronic unpredictable mild stress (CUMS) rats[J/OL]. Med Sci Monit, 2017, 23: 3080-3087 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/28644824/. DOI: 10.12659/msm.902549.
[31]
TAN Y K, ZHANG C G, TANG C H, et al. Differences and correlations of biochemical index levels in patients with bipolar disorder and major depressive disorder during a stable period[J/OL]. Medicine, 2023, 102(25): e34172 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/37352030/. DOI: 10.1097/MD.0000000000034172.
[32]
JIANG X Y, HUANG W X, WANG X M, et al. Effects of serotonin transporter knockout on glutamate and γ-aminobutyric acid systems in mouse cerebral cortex[J]. Chin J Prev Contr Chronic Dis, 2023, 31(8): 636-640. DOI: 10.16386/j.cjpccd.issn.1004-6194.2023.08.015.
[33]
WANG G L, AN T Y, LEI C, et al. Antidepressant-like effect of ginsenoside Rb1 on potentiating synaptic plasticity via the miR-134-mediated BDNF signaling pathway in a mouse model of chronic stress-induced depression[J]. J Ginseng Res, 2022, 46(3): 376-386. DOI: 10.1016/j.jgr.2021.03.005.
[34]
LIU S B, XU S L, WANG Z J, et al. Anti-depressant-like effect of sinomenine on chronic unpredictable mild stress-induced depression in a mouse model[J/OL]. Med Sci Monit, 2018, 24: 7646-7653 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/30362468/. DOI: 10.12659/MSM.908422.
[35]
LIN S S, ZHOU B, CHEN B J, et al. Electroacupuncture prevents astrocyte atrophy to alleviate depression[J/OL]. Cell Death Dis, 2023, 14(5): 343 [2024-07-19]. https://pubmed.ncbi.nlm.nih.gov/37248211/. DOI: 10.1038/s41419-023-05839-4.
[36]
PÁL B. Involvement of extrasynaptic glutamate in physiological and pathophysiological changes of neuronal excitability[J]. Cell Mol Life Sci, 2018, 75(16): 2917-2949. DOI: 10.1007/s00018-018-2837-5.

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