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The Effects of Stress on Glutamatergic Transmission in the Brain

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Abstract

Stress leads to detrimental effects on brain functions and results in various diseases. Recent studies highlight the involvement of glutamatergic transmission in pathogenesis of depressive behaviors and fears. Acute stress generates different impacts on the excitatory transmission compared to chronic stress. Different neuromodulators and epigenetic factors also participate in the alteration of synaptic transmission and the regulation of synaptic plasticity. Restoration of the glutamatergic transmission in stress-affected brain areas therefore provides novel directions of therapeutic interventions against stress.

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References

  1. Popoli M, Yan Z, McEwen BS et al (2012) The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 13:22–37

    CAS  Google Scholar 

  2. Reznikov LR, Grillo CA, Piroli GG et al (2007) Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressant treatment. Eur J Neurosci 25:3109–3114

    Article  PubMed  Google Scholar 

  3. Bagley J, Moghaddam B (1997) Temporal dynamics of glutamate efflux in the prefrontal cortex and in the hippocampus following repeated stress: effects of pretreatment with saline or diazepam. Neuroscience 77:65–73

    Article  CAS  PubMed  Google Scholar 

  4. Moghaddam B (1993) Stress preferentially increases extraneuronal levels of excitatory amino acids in the prefrontal cortex: comparison to hippocampus and basal ganglia. J Neurochem 60:1650–1657

    Article  CAS  PubMed  Google Scholar 

  5. Musazzi L, Milanese M, Farisello P et al (2010) Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants. PLoS One 5:e8566

    Article  PubMed Central  PubMed  Google Scholar 

  6. Treccani G, Musazzi L, Perego C et al (2014) Stress and corticosterone increase the readily releasable pool of glutamate vesicles in synaptic terminals of prefrontal and frontal cortex. Mol Psychiatry 19:433–443

    Article  CAS  PubMed  Google Scholar 

  7. Banasr M, Valentine GW, Li XY et al (2007) Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat. Biol Psychiatry 62:496–504

    Article  CAS  PubMed  Google Scholar 

  8. Leventopoulos M, Ruedi-Bettschen D, Knuesel I et al (2007) Long-term effects of early life deprivation on brain glia in Fischer rats. Brain Res 1142:119–126

    Article  CAS  PubMed  Google Scholar 

  9. Olivenza R, Moro MA, Lizasoain I et al (2000) Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex. J Neurochem 74:785–791

    Article  CAS  PubMed  Google Scholar 

  10. de Vasconcellos-Bittencourt AP, Vendite DA, Nassif M et al (2011) Chronic stress and lithium treatments alter hippocampal glutamate uptake and release in the rat and potentiate necrotic cellular death after oxygen and glucose deprivation. Neurochem Res 36:793–800

    Article  PubMed  Google Scholar 

  11. Yuen EY, Liu W, Karatsoreos IN et al (2009) Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proc Natl Acad Sci U S A 106:14075–14079

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Yuen EY, Liu W, Karatsoreos IN et al (2011) Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory. Mol Psychiatry 16:156–170

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Liu W, Yuen EY, Yan Z (2010) The stress hormone corticosterone increases synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors via serum- and glucocorticoid-inducible kinase (SGK) regulation of the GDI-Rab4 complex. J Biol Chem 285:6101–6108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Karst H, Joels M (2005) Corticosterone slowly enhances miniature excitatory postsynaptic current amplitude in mice CA1 hippocampal cells. J Neurophysiol 94:3479–3486

    Article  CAS  PubMed  Google Scholar 

  15. Saal D, Dong Y, Bonci A et al (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37:577–582

    Article  CAS  PubMed  Google Scholar 

  16. Campioni MR, Xu M, McGehee DS (2009) Stress-induced changes in nucleus accumbens glutamate synaptic plasticity. J Neurophysiol 101:3192–3198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Groc L, Choquet D, Chaouloff F (2008) The stress hormone corticosterone conditions AMPAR surface trafficking and synaptic potentiation. Nat Neurosci 11:868–870

    Article  CAS  PubMed  Google Scholar 

  18. Whitehead G, Jo J, Hogg EL et al (2013) Acute stress causes rapid synaptic insertion of Ca2+-permeable AMPA receptors to facilitate long-term potentiation in the hippocampus. Brain 136:3753–3765

    Article  PubMed Central  PubMed  Google Scholar 

  19. Gourley SL, Kedves AT, Olausson P et al (2009) A history of corticosterone exposure regulates fear extinction and cortical NR2B, GluR2/3, and BDNF. Neuropsychopharmacol 34:707–716

    Article  CAS  Google Scholar 

  20. Yuen EY, Wei J, Liu W et al (2012) Repeated stress causes cognitive impairment by suppressing glutamate receptor expression and function in prefrontal cortex. Neuron 73:962–977

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Karst H, Joels M (2003) Effect of chronic stress on synaptic currents in rat hippocampal dentate gyrus neurons. J Neurophysiol 89:625–633

    Article  PubMed  Google Scholar 

  22. Kallarackal AJ, Kvarta MD, Cammarata E et al (2013) Chronic stress induces a selective decrease in AMPA receptor-mediated synaptic excitation at hippocampal temporoammonic-CA1 synapses. J Neurosci 33:15669–15674

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Duric V, Banasr M, Stockmeier CA et al (2013) Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects. Int J Neuropsychopharmacol 16:69–82

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Hunter RG, Bellani R, Bloss E et al (2009) Regulation of kainate receptor subunit mRNA by stress and corticosteroids in the rat hippocampus. PLoS One 4:e4328

    Article  PubMed Central  PubMed  Google Scholar 

  25. Chaouloff F, Hemar A, Manzoni O (2007) Acute stress facilitates hippocampal CA1 metabotropic glutamate receptor-dependent long-term depression. J Neurosci 27:7130–7135

    Article  CAS  PubMed  Google Scholar 

  26. Hascup ER, Hascup KN, Pomerleau F et al (2012) An allosteric modulator of metabotropic glutamate receptors (mGluR(2)), (+)-TFMPIP, inhibits restraint stress-induced phasic glutamate release in rat prefrontal cortex. J Neurochem 122:619–627

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Gosnell HB, Silberman Y, Grueter BA et al (2011) mGluR8 modulates excitatory transmission in the bed nucleus of the stria terminalis in a stress-dependent manner. Neuropsychopharmacol 36:1599–1607

    Article  CAS  Google Scholar 

  28. Luscher C, Huber KM (2010) Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron 65:445–459

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Wei J, Yuen EY, Liu W et al (2014) Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition. Mol Psychiatry 19:588–598

    Article  CAS  PubMed  Google Scholar 

  30. Zhang H, Etherington LA, Hafner AS et al (2013) Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and antidepressant molecule. Mol Psychiatry 18:471–484

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Chen G, Greengard P, Yan Z (2004) Potentiation of NMDA receptor currents by dopamine D1 receptors in prefrontal cortex. Proc Natl Acad Sci U S A 101:2596–2600

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Wang J, O’Donnell P (2001) D(1) dopamine receptors potentiate nmda-mediated excitability increase in layer V prefrontal cortical pyramidal neurons. Cereb Cortex 11:452–462

    Article  CAS  PubMed  Google Scholar 

  33. Sarantis K, Matsokis N, Angelatou F (2009) Synergistic interactions of dopamine D1 and glutamate NMDA receptors in rat hippocampus and prefrontal cortex: involvement of ERK1/2 signaling. Neuroscience 163:1135–1145

    Article  CAS  PubMed  Google Scholar 

  34. Huppe-Gourgues F, O’Donnell P (2012) D(1)-NMDA receptor interactions in the rat nucleus accumbens change during adolescence. Synapse 66:584–591

    Article  CAS  PubMed  Google Scholar 

  35. Schilstrom B, Yaka R, Argilli E et al (2006) Cocaine enhances NMDA receptor-mediated currents in ventral tegmental area cells via dopamine D5 receptor-dependent redistribution of NMDA receptors. J Neurosci 26:8549–8558

    Article  CAS  PubMed  Google Scholar 

  36. Yuen EY, Zhong P, Li X et al (2013) Restoration of glutamatergic transmission by dopamine D4 receptors in stressed animals. J Biol Chem 288:26112–26120

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Cai X, Kallarackal AJ, Kvarta MD et al (2013) Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression. Nat Neurosci 16:464–472

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Sultan FA, Wang J, Tront J et al (2012) Genetic deletion of gadd45b, a regulator of active DNA demethylation, enhances long-term memory and synaptic plasticity. J Neurosci 32:17059–17066

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Day JJ, Childs D, Guzman-Karlsson MC et al (2013) DNA methylation regulates associative reward learning. Nat Neurosci 16:1445–1452

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Guan JS, Haggarty SJ, Giacometti E et al (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459:55–60

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Monteggia LM, Kavalali ET (2009) Rett syndrome and the impact of MeCP2 associated transcriptional mechanisms on neurotransmission. Biol Psychiatry 65:204–210

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Golden SA, Christoffel DJ, Heshmati M et al (2013) Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression. Nat Med 19:337–344

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Murgatroyd C, Patchev AV, Wu Y et al (2009) Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci 12:1559–1566

    Article  CAS  PubMed  Google Scholar 

  44. Elliott E, Ezra-Nevo G, Regev L et al (2010) Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice. Nat Neurosci 13:1351–1353

    Article  CAS  PubMed  Google Scholar 

  45. LaPlant Q, Vialou V, Covington HE 3rd et al (2010) Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat Neurosci 13:1137–1143

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Lee JB, Wei J, Liu W et al (2012) Histone deacetylase 6 gates the synaptic action of acute stress in prefrontal cortex. J Physiol 590:1535–1546

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Covington HE 3rd, Maze I, LaPlant QC et al (2009) Antidepressant actions of histone deacetylase inhibitors. J Neurosci 29:11451–11460

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Chaudhury D, Walsh JJ, Friedman AK et al (2013) Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493:532–536

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

TY is supported by “Hundred Talents Program” and “Qing Lan Project” of Nanjing Normal University. GH received grants from Science Philosophy Betterment Society (Registered British Virgin Islands).

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None declared.

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Correspondence to Ti-Fei Yuan.

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Yuan, TF., Hou, G. The Effects of Stress on Glutamatergic Transmission in the Brain. Mol Neurobiol 51, 1139–1143 (2015). https://doi.org/10.1007/s12035-014-8783-9

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  • DOI: https://doi.org/10.1007/s12035-014-8783-9

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