Mapping Changes in Glutamate with Glutamate-Weighted MRI in Forced Swim Test Model of Depression in Rats

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 Feb 24

PMID 38397986

Authors

Donghoon Lee

Chul-Woong Woo

Hwon Heo

Yousun Ko

Ji Sung Jang

Seongwon Na

Nari Kim

Dong-Cheol Woo

Kyung Won Kim

Do-Wan Lee

Affiliations

Soon will be listed here.

Abstract

Chemical exchange saturation transfer with glutamate (GluCEST) imaging is a novel technique for the non-invasive detection and quantification of cerebral Glu levels in neuromolecular processes. Here we used GluCEST imaging and H magnetic resonance spectroscopy (H MRS) to assess in vivo changes in Glu signals within the hippocampus in a rat model of depression induced by a forced swim test. The forced swimming test (FST) group exhibited markedly reduced GluCEST-weighted levels and Glu concentrations when examined using H MRS in the hippocampal region compared to the control group (GluCEST-weighted levels: 3.67 ± 0.81% vs. 5.02 ± 0.44%, < 0.001; and Glu concentrations: 6.560 ± 0.292 μmol/g vs. 7.133 ± 0.397 μmol/g, = 0.001). Our results indicate that GluCEST imaging is a distinctive approach to detecting and monitoring Glu levels in a rat model of depression. Furthermore, the application of GluCEST imaging may provide a deeper insight into the neurochemical involvement of glutamate in various psychiatric disorders.

References

Filatova E, Shadrina M, Slominsky P . Major Depression: One Brain, One Disease, One Set of Intertwined Processes. Cells. 2021; 10(6). PMC: 8224372. DOI: 10.3390/cells10061283. View

Manji H, Quiroz J, Sporn J, Payne J, Denicoff K, Gray N . Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry. 2003; 53(8):707-42. DOI: 10.1016/s0006-3223(03)00117-3. View

Lee D, Heo H, Woo C, Woo D, Kim J, Kim K . Temporal Changes in In Vivo Glutamate Signal during Demyelination and Remyelination in the Corpus Callosum: A Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging Study. Int J Mol Sci. 2020; 21(24). PMC: 7764201. DOI: 10.3390/ijms21249468. View

Pavlova I, Ruda-Kucerova J . Brain metabolic derangements examined using H MRS and their (in)consistency among different rodent models of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2023; 127:110808. DOI: 10.1016/j.pnpbp.2023.110808. View

Bagga P, Crescenzi R, Krishnamoorthy G, Verma G, Nanga R, Reddy D . Mapping the alterations in glutamate with GluCEST MRI in a mouse model of dopamine deficiency. J Neurochem. 2016; 139(3):432-439. PMC: 5077646. DOI: 10.1111/jnc.13771. View

Bidzinski A, Jankowska E, Pucilowski O . Antidepressant-like action of nicardipine, verapamil and hemicholinium-3 injected into the anterior hypothalamus in the rat forced swim test. Pharmacol Biochem Behav. 1990; 36(4):795-8. DOI: 10.1016/0091-3057(90)90079-w. View

Schulz D, Smith D, Yu M, Lee H, Henn F . Selective breeding for helplessness in rats alters the metabolic profile of the hippocampus and frontal cortex: a 1H-MRS study at 9.4 T. Int J Neuropsychopharmacol. 2012; 16(1):199-212. DOI: 10.1017/S1461145711001994. View

Gold P . The organization of the stress system and its dysregulation in depressive illness. Mol Psychiatry. 2014; 20(1):32-47. DOI: 10.1038/mp.2014.163. View

Hashimoto K, Bruno D, Nierenberg J, Marmar C, Zetterberg H, Blennow K . Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study. Transl Psychiatry. 2016; 6:e744. PMC: 4872461. DOI: 10.1038/tp.2016.8. View

10.

Sekar S, Grandjean J, Garnell J, Willems R, Duytschaever H, Seramani S . Neuro-metabolite profiles of rodent models of psychiatric dysfunctions characterised by MR spectroscopy. Neuropharmacology. 2018; 146:109-116. DOI: 10.1016/j.neuropharm.2018.11.021. View

11.

Rojas P, Serrano-Garcia N, Medina-Campos O, Pedraza-Chaverri J, Ogren S, Rojas C . Antidepressant-like effect of a Ginkgo biloba extract (EGb761) in the mouse forced swimming test: role of oxidative stress. Neurochem Int. 2011; 59(5):628-36. DOI: 10.1016/j.neuint.2011.05.007. View

12.

Roalf D, Nanga R, Rupert P, Hariharan H, Quarmley M, Calkins M . Glutamate imaging (GluCEST) reveals lower brain GluCEST contrast in patients on the psychosis spectrum. Mol Psychiatry. 2017; 22(9):1298-1305. PMC: 5822706. DOI: 10.1038/mp.2016.258. View

13.

Lee D, Heo H, Woo D, Kim J, Lee D . Amide Proton Transfer-weighted 7-T MRI Contrast of Myelination after Cuprizone Administration. Radiology. 2021; 299(2):428-434. DOI: 10.1148/radiol.2021203766. View

14.

Lee D, Kwon J, Heo H, Woo C, Yu N, Kim K . Cerebral Glutamate Alterations Using Chemical Exchange Saturation Transfer Imaging in a Rat Model of Lipopolysaccharide-Induced Sepsis. Metabolites. 2023; 13(5). PMC: 10224036. DOI: 10.3390/metabo13050636. View

15.

Lee A, Ogle W, Sapolsky R . Stress and depression: possible links to neuron death in the hippocampus. Bipolar Disord. 2002; 4(2):117-28. DOI: 10.1034/j.1399-5618.2002.01144.x. View

16.

Lu C, Lin T, Huang S, Wang S . 5-HT receptor agonist CGS12066 presynaptically inhibits glutamate release in rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 2018; 86:122-130. DOI: 10.1016/j.pnpbp.2018.05.019. View

17.

Draganov M, Vives-Gilabert Y, de Diego-Adelino J, Vicent-Gil M, Puigdemont D, Portella M . Glutamatergic and GABA-ergic abnormalities in First-episode depression. A 1-year follow-up 1H-MR spectroscopic study. J Affect Disord. 2020; 266:572-577. DOI: 10.1016/j.jad.2020.01.138. View

18.

Kessler R, Chiu W, Demler O, Merikangas K, Walters E . Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005; 62(6):617-27. PMC: 2847357. DOI: 10.1001/archpsyc.62.6.617. View

19.

Maeng S, Zarate Jr C . The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Curr Psychiatry Rep. 2008; 9(6):467-74. DOI: 10.1007/s11920-007-0063-1. View

20.

Cai K, Haris M, Singh A, Kogan F, Greenberg J, Hariharan H . Magnetic resonance imaging of glutamate. Nat Med. 2012; 18(2):302-6. PMC: 3274604. DOI: 10.1038/nm.2615. View