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Dysregulation of the glutamatergic receptors after antidepressant treatment in human neural progenitor cells

Molecular Psychiatry volume 22, pages 1228–1229 (2017)Cite this article

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Glutamate is the major mediator of excitatory synaptic transmission in the mammalian brain,1 and accumulating evidence points to a potential role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Gray et al.2 recently reported a generalized dysregulation of glutamatergic receptors (GluRs) in the postmortem brains of depressed suicide completers, suggesting that the glutamatergic system should be considered an important mediator of psychiatric pathology and, potentially, also a common pathway for the therapeutic action of antidepressant agents.3 To resolve this hypothesis, important information may be obtained from the target and off-target effect of commonly used antidepressants.

Glutamate is an excitatory neurotransmitter that is widely distributed in the brain, exerting its effects through the stimulation of several GluR subtypes. These include the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA), kainate receptors (KAR) as well as metabotropic (mGluR) receptors encoded by 24 different genes.4 To address the question of how commonly prescribed antidepressants affect RNA expression in the glutamate system, we took advantage of an in vitro model previously shown to have a serotonergic phenotype.5 Specifically, we treated human neural progenitor cells (NPCs) with citalopram and imipramine, and quantified expression changes of 20 GluR genes using TaqMan assays (Applied Biosystems, Foster City, CA, USA). Expression of GRIK3 was not detectable in this cell line at quantifiable levels. Antidepressants were applied at nontoxic clinically relevant concentrations of either 50 μm citalopram hydrobromide, 12.5 μm imipramine hydrochloride or no-drug control for 15 days (chronic). The NPCs employed in this study were derived from a healthy male individual. This paradigm did not allow us to test the gender differences observed by Gray et al.2 in postmortem brains, but rather provided a gender-neutral environment from the point of view of hormones for both the treatment and the control conditions.

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References

  1. Orrego F, Villanueva S . The chemical nature of the main central excitatory transmitter: a critical appraisal based upon release studies and synaptic vesicle localization. Neuroscience 1993; 56: 539–555.

    Article  CAS  PubMed  Google Scholar 

  2. Gray AL, Hyde TM, Deep-Soboslay A, Kleinman JE, Sodhi MS . Sex differences in glutamate receptor gene expression in major depression and suicide. Mol Psychiatry 2015; 20: 1057–1068.

    Article  CAS  PubMed  Google Scholar 

  3. Sanacora G, Treccani G, Popoli M . Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology 2012; 62: 63–77.

    Article  CAS  PubMed  Google Scholar 

  4. Lodge D . The history of the pharmacology and cloning of ionotropic glutamate receptors and the development of idiosyncratic nomenclature. Neuropharmacology 2009; 56: 6–21.

    Article  CAS  PubMed  Google Scholar 

  5. Lopez JP, Lim R, Cruceanu C, Crapper L, Fasano C, Labonte B et al. miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment. Nat Med 2014; 20: 764–768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lambe EK, Aghajanian GK . Hallucinogen-induced UP states in the brain slice of rat prefrontal cortex: role of glutamate spillover and NR2B-NMDA receptors. Neuropsychopharmacology 2006; 31: 1682–1689.

    Article  CAS  PubMed  Google Scholar 

  7. Sanacora G, Zarate CA, Krystal JH, Manji HK . Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 2008; 7: 426–437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Swanson CJ, Bures M, Johnson MP, Linden AM, Monn JA, Schoepp DD . Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 2005; 4: 131–144.

    Article  CAS  PubMed  Google Scholar 

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  1. C Cruceanu and J P Lopez: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada

    C Cruceanu, J P Lopez, W-T Tsai & G Turecki

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  1. C Cruceanu
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  2. J P Lopez
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  3. W-T Tsai
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  4. G Turecki
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Correspondence to G Turecki.

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Cruceanu, C., Lopez, J., Tsai, WT. et al. Dysregulation of the glutamatergic receptors after antidepressant treatment in human neural progenitor cells. Mol Psychiatry 22, 1228–1229 (2017). https://doi.org/10.1038/mp.2016.138

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