Inflammation effects on brain glutamate in depression: Mechanistic considerations and treatment implications

Current Topics in Behavioral Neurosciences

Volumn 31, Issue , 2017, Pages

  Haroon, Ebrahim ^a   Miller, Andrew H ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cytokines; Depression; Glia; Glutamate; Inflammation; Magnetic resonance imaging; Neuroimaging

Indexed keywords

ALPHA INTERFERON; ANION CHANNEL; C REACTIVE PROTEIN; CYCLOOXYGENASE 2; CYTOKINE; ENDOTOXIN; GLUTAMATE AMMONIA LIGASE; GLUTAMATE RECEPTOR; GLUTAMIC ACID; INTERLEUKIN 6; TUMOR NECROSIS FACTOR; AMINO ACID RECEPTOR BLOCKING AGENT;

ANHEDONIA; ASTROCYTE; CELL CYCLE REGULATION; CELL SWELLING; CHRONIC STRESS; DEPRESSION; EXCITOTOXICITY; HUMAN; INFLAMMATION; MOOD DISORDER; NEUROTRANSMISSION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OBESITY; PRIORITY JOURNAL; PSYCHOMOTOR RETARDATION; ANIMAL; METABOLISM;

ANIMALS; DEPRESSION; EXCITATORY AMINO ACID ANTAGONISTS; GLUTAMIC ACID; HUMANS; INFLAMMATION;

EID: 85007552232     PISSN: 18663370     EISSN: 18663389     Source Type: Book Series    
DOI: 10.1007/7854_2016_40     Document Type: Chapter

References (140)

1. CDC (2015) Suicide-facts at a glance 2015. Centers for Disease Control, Atlanta, GA, USA
2. Pratt LA, Brody DJ (2014) Depression in the U.S. Household Population, 2009–2012. NCHS Data Brief #172. National Center for Health Statistics, Haysviille, MD
3. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 163(11):1905–1917. doi:10.1176/appi.ajp.163.11.1905
4. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9 (1):46–56. doi:10.1038/nrn2297
5. Dantzer R, Walker A (2014) Is there a role for glutamate-mediated excitotoxicity in inflammation-induced depression? J Neural Transm. doi:10.1007/s00702-014-1187-1
6. Duman RS (2014) Pathophysiology of depression and innovative treatments: remodeling glutamatergic synaptic connections. Dialogues Clin Neurosci 16(1):11–27
7. Hodes GE, Kana V, Menard C, Merad M, Russo SJ (2015) Neuroimmune mechanisms of depression. Nat Neurosci 18(10):1386–1393. doi:10.1038/nn.4113
8. Lener MS, Niciu MJ, Ballard ED, Park M, Park LT, Nugent A, Zarate CA (2016) Glutamate and GABA systems in the pathophysiology of major depression and antidepressant response to ketamine. Biol Psychiatry. doi:10.1016/j.biopsych.2016.05.005
9. Miller AH, Raison CL (2016) The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol 16(1):22–34. doi:10.1038/nri.2015.5
10. Sanacora G, Zarate CA, Krystal JH, Manji HK (2008) Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 7 (5):426–437. doi:10.1038/nrd2462
11. Zarate C Jr., Machado-Vieira R, Henter I, Ibrahim L, Diazgranados N, Salvadore G (2010) Glutamatergic modulators: the future of treating mood disorders? Harv Rev Psychiatry 18 (5):293–303. doi:10.3109/10673229.2010.511059
12. Haroon E, Fleischer CC, Felger JC, Chen X, Woolwine BJ, Patel T, Hu XP, Miller AH (2016) Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression. Mol Psychiatry. doi:10.1038/mp.2015.206
13. Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65:732–741. doi:10.1016/j.biopsych.2008.11.029
14. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67(5):446–457. doi:10.1016/j.biopsych.2009.09.033
15. Haapakoski R, Mathieu J, Ebmeier KP, Alenius H, Kivimaki M (2015) Cumulative metaanalysis of interleukins 6 and 1beta, tumour necrosis factor alpha and C-reactive protein in patients with major depressive disorder. Brain Behav Immun. doi:10.1016/j.bbi.2015.06.001
16. Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71(2):171–186. doi:10.1097/PSY.0b013e3181907c1b
17. Bufalino C, Hepgul N, Aguglia E, Pariante CM (2012) The role of immune genes in the association between depression and inflammation: a review of recent clinical studies. Brain Behav Immun. doi:10.1016/j.bbi.2012.04.009
18. Cattaneo A, Gennarelli M, Uher R, Breen G, Farmer A, Aitchison KJ, Craig IW, Anacker C, Zunsztain PA, McGuffin P, Pariante CM (2013) Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline ‘predictors’ and longitudinal ‘targets’. Neuropsychopharmacology 38(3):377–385. doi:10.1038/npp.2012.191
19. Sluzewska A, Sobieska M, Rybakowski JK (1997) Changes in acute-phase proteins during lithium potentiation of antidepressants in refractory depression. Neuropsychobiology 35 (3):123–127
20. Raison CL, Felger JC, Miller AH (2013) Inflammation and treatment resistance in major depression: a perfect storm. Psychiatric Times, September 12
21. Felger JC, Li L, Marvar PJ, Woolwine BJ, Harrison DG, Raison CL, Miller AH (2013) Tyrosine metabolism during interferon-alpha administration: association with fatigue and CSF dopamine concentrations. Brain Behav Immun 31:153–160. doi:10.1016/j.bbi.2012.10.010
22. Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22(4):370–379. doi:10.1016/s0893-133x(99)00134-7
23. Strawbridge R, Arnone D, Danese A, Papadopoulos A, Herane Vives A, Cleare AJ (2015) Inflammation and clinical response to treatment in depression: a meta-analysis. Eur Neuropsychopharmacol 25(10):1532–1543. doi:10.1016/j.euroneuro.2015.06.007
24. Capuron L, Gumnick JF, Musselman DL, Lawson DH, Reemsnyder A, Nemeroff CB, Miller AH (2002) Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 26 (5):643–652
25. Constant A, Castera L, Dantzer R, Couzigou P, de Ledinghen V, Demotes-Mainard J, Henry C (2005) Mood alterations during interferon-alfa therapy in patients with chronic hepatitis C: evidence for an overlap between manic/hypomanic and depressive symptoms. J Clin Psychiatry 66(8):1050–1057
26. Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR (2010) Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Biol Psychiatry 68(8):748–754. doi:10.1016/j.biopsych.2010.06.010
27. Eisenberger NI, Inagaki TK, Mashal NM, Irwin MR (2010) Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav Immun 24(4):558–563. doi:10.1016/j.bbi.2009.12.009
28. Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD (2009) Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry 66:407–414. doi:10.1016/j.biopsych.2009.03.015
29. Evans DL, Charney DS, Lewis L, Golden RN, Gorman JM, Krishnan KR, Nemeroff CB, Bremner JD, Carney RM, Coyne JC, Delong MR, Frasure-Smith N, Glassman AH, Gold PW, Grant I, Gwyther L, Ironson G, Johnson RL, Kanner AM, Katon WJ, Kaufmann PG, Keefe FJ, Ketter T, Laughren TP, Leserman J, Lyketsos CG, McDonald WM, McEwen BS, Miller AH, Musselman D, O’Connor C, Petitto JM, Pollock BG, Robinson RG, Roose SP, Rowland J, Sheline Y, Sheps DS, Simon G, Spiegel D, Stunkard A, Sunderland T, Tibbits P Jr., Valvo WJ (2005) Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry 58(3):175–189. doi:10.1016/j.biopsych.2005.05.001
30. Kohler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, Krogh J (2014) Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 71(12):1381–1391. doi:10.1001/jamapsychiatry.2014.1611
31. Abbasi SH, Hosseini F, Modabbernia A, Ashrafi M, Akhondzadeh S (2012) Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study. J Affect Disord 141(2–3):308–314. doi:10.1016/j.jad.2012.03.033
32. Akhondzadeh S, Jafari S, Raisi F, Nasehi AA, Ghoreishi A, Salehi B, Mohebbi-Rasa S, Raznahan M, Kamalipour A (2009) Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety 26 (7):607–611. doi:10.1002/da.20589
33. Hashemian F, Majd M, Hosseini SM, Sharifi A, Panahi MVS, Bigdeli O (2011) A randomized, double-blind, placebo-controlled trial of celecoxib augmentation of sertraline in the treatment of a drug-naive women with major depression. Klinik Psikofarmakoloji Bulteni 21: S183–S184
34. Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Moller HJ, Arolt V, Riedel M (2006) The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 11(7):680–684
35. Na KS, Lee KJ, Lee JS, Cho YS, Jung HY (2014) Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 48:79–85. doi:10.1016/j.pnpbp.2013.09.006
36. Faridhosseini F, Sadeghi R, Farid L, Pourgholami M (2014) Celecoxib: a new augmentation strategy for depressive mood episodes. A systematic review and meta-analysis of randomized placebo-controlled trials. Hum Psychopharmacol 29(3):216–223. doi:10.1002/hup.2401
37. Miller AH, Raison CL (2015) Are anti-inflammatory therapies viable treatments for psychiatric disorders?: where the rubber meets the road. JAMA Psychiatry 72(6):527–528. doi:10.1001/jamapsychiatry.2015.22
38. Jansen JF, Backes WH, Nicolay K, Kooi ME (2006) 1H MR spectroscopy of the brain: absolute quantification of metabolites. Radiology 240(2):318–332. doi:10.1148/radiol.2402050314
39. Mason GF, Krystal JH (2006) MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases. NMR Biomed 19(6):690–701. doi:10.1002/nbm.1080
40. Moore CM, Frederick BB, Renshaw PF (1999) Brain biochemistry using magnetic resonance spectroscopy: relevance to psychiatric illness in the elderly. J Geriatr Psychiatry Neurol 12 (3):107–117
41. Stagg CJ, Bestmann S, Constantinescu AO, Moreno LM, Allman C, Mekle R, Woolrich M, Near J, Johansen-Berg H, Rothwell JC (2011) Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex. J Physiol 589 (Pt 23):5845–5855. doi:10.1113/jphysiol.2011.216978
42. Tremblay S, Beaule V, Proulx S, de Beaumont L, Marjanska M, Doyon J, Pascual-Leone A, Lassonde M, Theoret H (2013) Relationship between transcranial magnetic stimulation measures of intracortical inhibition and spectroscopy measures of GABA and glutamate + glutamine. J Neurophysiol 109(5):1343–1349. doi:10.1152/jn.00704.2012
43. Yildiz-Yesiloglu A, Ankerst DP (2006) Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: a meta-analysis. Psychiatry Res 147(1):1–25. doi:10.1016/j.pscychresns.2005.12.004
44. Yuksel C, Ongur D (2010) Magnetic resonance spectroscopy studies of glutamate-related abnormalities in mood disorders. Biol Psychiatry 68(9):785–794. doi:10.1016/j.biopsych.2010.06.016
45. Rosenberg DR, Paulson ND, Seraji-Bozorgard N, Wilds IB, Stewart CM, Moore GJ (2000) Brain chemistry in pediatric depression. Biol Psychiatry 47:95S
46. Kondo DG, Hellem TL, Sung YH, Kim N, Jeong EK, Delmastro KK, Shi X, Renshaw PF (2011) Review: magnetic resonance spectroscopy studies of pediatric major depressive disorder. Depress Res Treat 2011:650450. doi:10.1155/2011/650450
47. Luykx JJ, Laban KG, van den Heuvel MP, Boks MP, Mandl RC, Kahn RS, Bakker SC (2012) Region and state specific glutamate downregulation in major depressive disorder: a metaanalysis of (1)H-MRS findings. Neurosci Biobehav Rev 36(1):198–205. doi:10.1016/j.neubiorev.2011.05.014
48. Arnone D, Mumuni AN, Jauhar S, Condon B, Cavanagh J (2015) Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations. Eur Neuropsychopharmacol 25(8):1109–1117. doi:10.1016/j.euroneuro.2015.04.016
49. Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B (2003) Metabolic changes within the left dorsolateral prefrontal cortex occurring with electroconvulsive therapy in patients with treatment resistant unipolar depression. Psychol Med 33(7):1277–1284
50. Pfleiderer B, Michael N, Erfurth A, Ohrmann P, Hohmann U, Wolgast M, Fiebich M, Arolt V, Heindel W (2003) Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatry Res 122 (3):185–192
51. Zhang J, Narr KL, Woods RP, Phillips OR, Alger JR, Espinoza RT (2013) Glutamate normalization with ECT treatment response in major depression. Mol Psychiatry 18 (3):268–270. doi:10.1038/mp.2012.46
52. Taylor M, Murphy SE, Selvaraj S, Wylezinkska M, Jezzard P, Cowen PJ, Evans J (2008) Differential effects of citalopram and reboxetine on cortical Glx measured with proton MR spectroscopy. J Psychopharmacol 22(5):473–476. doi:10.1177/0269881107081510
53. Murck H, Schubert MI, Schmid D, Schussler P, Steiger A, Auer DP (2009) The glutamatergic system and its relation to the clinical effect of therapeutic-sleep deprivation in depression-an MR spectroscopy study. J Psychiatr Res 43(3):175–180. doi:10.1016/j.jpsychires.2008.04.009
54. Valentine GW, Mason GF, Gomez R, Fasula M, Watzl J, Pittman B, Krystal JH, Sanacora G (2011) The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS. Psychiatry Res 191 (2):122–127. doi:10.1016/j.pscychresns.2010.10.009
55. Niciu MJ, Ionescu DF, Richards EM, CA Z Jr. (2014) Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder. J Neural Transm 121 (8):907–924. doi:10.1007/s00702-013-1130-x
56. Walker AK, Budac DP, Bisulco S, Lee AW, Smith RA, Beenders B, Kelley KW, Dantzer R (2013) NMDA receptor blockade by ketamine abrogates lipopolysaccharide-induced depressive-like behavior in C57BL/6 J mice. Neuropsychopharmacology 38(9):1609–1616. doi:10.1038/npp.2013.71
57. Abdallah CG, Jiang L, De Feyter HM, Fasula M, Krystal JH, Rothman DL, Mason GF, Sanacora G (2014) Glutamate metabolism in major depressive disorder. Am J Psychiatry 171 (12):1320–1327. doi:10.1176/appi.ajp.2014.14010067
58. Bluml S, Moreno-Torres A, Shic F, Nguy CH, Ross BD (2002) Tricarboxylic acid cycle of glia in the in vivo human brain. NMR Biomed 15(1):1–5
59. Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN (2012) Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis. Bipolar Disord 14(5):478–487. doi:10.1111/j.1399-5618.2012.01033.x
60. Bernard R, Kerman IA, Thompson RC, Jones EG, Bunney WE, Barchas JD, Schatzberg AF, Myers RM, Akil H, Watson SJ (2011) Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression. Mol Psychiatry 16(6):634–646. doi:10.1038/mp.2010.44
61. Ernst C, Mechawar N, Turecki G (2009) Suicide neurobiology. Prog Neurobiol 89 (4):315–333. doi:10.1016/j.pneurobio.2009.09.001
62. Ongur D, Bechtholt AJ, Carlezon WA Jr., Cohen BM (2014) Glial abnormalities in mood disorders. Harv Rev Psychiatry 22(6):334–337. doi:10.1097/HRP.0000000000000060
63. Rajkowska G, Stockmeier CA (2013) Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue. Curr Drug Targets 14(11):1225–1236
64. Nagy C, Suderman M, Yang J, Szyf M, Mechawar N, Ernst C, Turecki G (2015) Astrocytic abnormalities and global DNA methylation patterns in depression and suicide. Mol Psychiatry 20(3):320–328. doi:10.1038/mp.2014.21
65. Torres-Platas SG, Hercher C, Davoli MA, Maussion G, Labonte B, Turecki G, Mechawar N (2011) Astrocytic hypertrophy in anterior cingulate white matter of depressed suicides. Neuropsychopharmacology 36(13):2650–2658. doi:10.1038/npp.2011.154
66. Rajkowska G, Miguel-Hidalgo JJ (2007) Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 6(3):219–233
67. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, Overholser JC, Roth BL, Stockmeier CA (1999) Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 45(9):1085–1098
68. Choudary PV, Molnar M, Evans SJ, Tomita H, Li JZ, Vawter MP, Myers RM, Bunney WE, Jr., Akil H, Watson SJ, Jones EG (2005) Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci U S A 102 (43):15653–15658. doi:10.1073/pnas.0507901102
69. Barley K, Dracheva S, Byne W (2009) Subcortical oligodendrocyte-and astrocyte-associated gene expression in subjects with schizophrenia, major depression and bipolar disorder. Schizophr Res 112(1–3):54–64. doi:10.1016/j.schres.2009.04.019
70. Sequeira A, Mamdani F, Ernst C, Vawter MP, Bunney WE, Lebel V, Rehal S, Klempan T, Gratton A, Benkelfat C, Rouleau GA, Mechawar N, Turecki G (2009) Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression. PLoS One 4(8):e6585. doi:10.1371/journal.pone.0006585
71. Zhang C, Li Z, Wu Z, Chen J, Wang Z, Peng D, Hong W, Yuan C, Wang Z, Yu S, Xu Y, Xu L, Xiao Z, Fang Y (2014) A study of N-methyl-D-aspartate receptor gene (GRIN2B) variants as predictors of treatment-resistant major depression. Psychopharmacology (Berl) 231(4):685–693. doi:10.1007/s00213-013-3297-0
72. Bechtholt-Gompf AJ, Walther HV, Adams MA, Carlezon WA Jr., Ongur D, Cohen BM (2010) Blockade of astrocytic glutamate uptake in rats induces signs of anhedonia and impaired spatial memory. Neuropsychopharmacology 35(10):2049–2059. doi:10.1038/npp.2010.74
73. Popoli M, Yan Z, McEwen BS, Sanacora G (2012) The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 13(1):22–37. doi:10.1038/nrn3138
74. Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65(1):1–105. doi:10.1016/s0301-0082(00)00067-8
75. Jabaudon D, Scanziani M, Gahwiler BH, Gerber U (2000) Acute decrease in net glutamate uptake during energy deprivation. Proc Natl Acad Sci U S A 97(10):5610–5615
76. Jabaudon D, Shimamoto K, Yasuda-Kamatani Y, Scanziani M, Gahwiler BH, Gerber U (1999) Inhibition of uptake unmasks rapid extracellular turnover of glutamate of nonvesicular origin. Proc Natl Acad Sci U S A 96(15):8733–8738
77. Dantzer R, O’Connor JC, Lawson MA, Kelley KW (2011) Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology 36(3):426–436. doi:10.1016/j.psyneuen.2010.09.012
78. Lewerenz J, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW, Massie A, Smolders I, Methner A, Pergande M, Smith SB, Ganapathy V, Maher P (2013) The cystine/glutamate antiporter system x(c)(—) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid Redox Signal 18(5):522–555. doi:10.1089/ars.2011.4391
79. Malarkey E, Parpura V (2008) Mechanisms of glutamate release from astrocytes. Neurochem Int 52(1–2):142–154. doi:10.1016/j.neuint.2007.06.005
80. Petrelli F, Bezzi P (2016) Novel insights into gliotransmitters. Curr Opin Pharmacol 26:138–145. doi:10.1016/j.coph.2015.11.010
81. Tilleux S, Hermans E (2007) Neuroinflammation and regulation of glial glutamate uptake in neurological disorders. J Neurosci Res 85(10):2059–2070. doi:10.1002/jnr.21325
82. 2+ signaling triggers astrocytic glutamate release. J Neurosci 33(44):17404–17412. doi:10.1523/JNEUROSCI.2178-13.2013
83. Ye ZC, Sontheimer H (1996) Cytokine modulation of glial glutamate uptake: a possible involvement of nitric oxide. Neuroreport 7(13):2181–2185
84. Zhou Y, Danbolt NC (2014) Glutamate as a neurotransmitter in the healthy brain. J Neural Transm (Vienna) 121(8):799–817. doi:10.1007/s00702-014-1180-8
85. Nedergaard M, Takano T, Hansen AJ (2002) Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci 3(9):748–755. doi:10.1038/nrn916
86. Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky B, Orrenius S, Lipton SA, Nicotera P (1995) Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15(4):961–973
87. Rothstein JD (1996) Excitotoxicity hypothesis. Neurology 47(4 Suppl 2):S19–S26
88. Hardingham GE, Bading H (2010) Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci 11(10):682–696. doi:10.1038/nrn2911
89. Hardingham GE, Fukunaga Y, Bading H (2002) Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci 5(5):405–414. doi:10.1038/nn835
90. Leibowitz A, Boyko M, Shapira Y, Zlotnik A (2012) Blood glutamate scavenging: insight into neuroprotection. Int J Mol Sci 13(8):10041–10066. doi:10.3390/ijms130810041
91. Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, Miller AH (2003) Interferon-alpha-induced changes in tryptophan metabolism. Relationship to depression and paroxetine treatment. Biol Psychiatry 54(9):906–914. doi:10.1016/s0006-3223(03)00173-2
92. Goshen I, Yirmiya R (2009) Interleukin-1 (IL-1): a central regulator of stress responses. Front Neuroendocrinol 30(1):30–45. doi:10.1016/j.yfrne.2008.10.001
93. Halassa MM, Fellin T, Haydon PG (2007) The tripartite synapse: roles for gliotransmission in health and disease. Trends Mol Med 13(2):54–63. doi:10.1016/j.molmed.2006.12.005
94. Iliff JJ, Nedergaard M (2013) Is there a cerebral lymphatic system? Stroke 44(6 Suppl 1): S93–S95. doi:10.1161/STROKEAHA.112.678698
95. Parpura V, Verkhratsky A (2013) Astroglial amino acid-based transmitter receptors. Amino Acids 44(4):1151–1158. doi:10.1007/s00726-013-1458-4
96. Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6(8):626–640. doi:10.1038/nrn1722
97. Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E, Vescovi A, Bagetta G, Kollias G, Meldolesi J, Volterra A (2001) CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci 4(7):702–710. doi:10.1038/89490
98. Lewerenz J, Maher P (2015) Chronic glutamate toxicity in neurodegenerative diseases-what is the evidence? Front Neurosci 9:469. doi:10.3389/fnins.2015.00469
99. Nathan C, Cunningham-Bussel A (2013) Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat Rev Immunol 13(5):349–361. doi:10.1038/nri3423
100. Murugan M, Ling E-A, Kaur C (2013) Glutamate receptors in microglia. CNS Neurol Disord Drug Targets 12(6):773–784. doi:10.2174/18715273113126660174
101. Takaki J, Fujimori K, Miura M, Suzuki T, Sekino Y, Sato K (2012) L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation: the ‘collusion’ hypothesis for increased extracellular L-glutamate concentration in neuroinflammation. J Neuroinflammation 9:275. doi:10.1186/1742-2094-9-275
102. Persson M, Brantefjord M, Hansson E, Ronnback L (2005) Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-alpha. Glia 51(2):111–120. doi:10.1002/glia.20191
103. Yirmiya R, Goshen I (2011) Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun 25(2):181–213. doi:10.1016/j.bbi.2010.10.015
104. Yirmiya R, Rimmerman N, Reshef R (2015) Depression as a microglial disease. Trends Neurosci 38(10):637–658. doi:10.1016/j.tins.2015.08.001
105. Gras G, Samah B, Hubert A, Leone C, Porcheray F, Rimaniol AC (2012) EAAT expression by macrophages and microglia: still more questions than answers. Amino Acids 42 (1):221–229. doi:10.1007/s00726-011-0866-6
106. Fleshner M (2013) Stress-evoked sterile inflammation, danger associated molecular patterns (DAMPs), microbial associated molecular patterns (MAMPs) and the inflammasome. Brain Behav Immun 27(1):1–7. doi:10.1016/j.bbi.2012.08.012
107. Iwata M, Ota KT, Li XY, Sakaue F, Li N, Dutheil S, Banasr M, Duric V, Yamanashi T, Kaneko K, Rasmussen K, Glasebrook A, Koester A, Song D, Jones KA, Zorn S, Smagin G, Duman RS (2015) Psychological stress activates the inflammasome via release of adenosine triphosphate and stimulation of the purinergic type 2X7 receptor. Biol Psychiatry. doi:10.1016/j.biopsych.2015.11.026
108. Duan S, Anderson CM, Keung EC, Chen Y, Chen Y, Swanson RA (2003) P2X7 receptormediated release of excitatory amino acids from astrocytes. J Neurosci 23(4):1320–1328
109. Sitcheran R, Gupta P, Fisher PB, Baldwin AS (2005) Positive and negative regulation of EAAT2 by NF-kappaB: a role for N-myc in TNFalpha-controlled repression. EMBO J 24 (3):510–520. doi:10.1038/sj.emboj.7600555
110. Korn T, Magnus T, Jung S (2005) Autoantigen specific T cells inhibit glutamate uptake in astrocytes by decreasing expression of astrocytic glutamate transporter GLAST: a mechanism mediated by tumor necrosis factor-alpha. FASEB J 19(13):1878–1880. doi:10.1096/fj.05-3748fje
111. Ohgoh M, Hanada T, Smith T, Hashimoto T, Ueno M, Yamanishi Y, Watanabe M, Nishizawa Y (2002) Altered expression of glutamate transporters in experimental autoimmune encephalomyelitis. J Neuroimmunol 125(1–2):170–178
112. Szymocha R, Akaoka H, Dutuit M, Malcus C, Didier-Bazes M, Belin MF, Giraudon P (2000) Human T-cell lymphotropic virus type 1-infected T lymphocytes impair catabolism and uptake of glutamate by astrocytes via tax-1 and tumor necrosis factor alpha. J Virol 74 (14):6433–6441. doi:10.1128/jvi.74.14.6433-6441.2000
113. Vercellino M, Merola A, Piacentino C, Votta B, Capello E, Mancardi GL, Mutani R, Giordana MT, Cavalla P (2007) Altered glutamate reuptake in relapsing–remitting and secondary progressive multiple sclerosis cortex: correlation with microglia infiltration, demyelination, and neuronal and synaptic damage. J Neuropathol Exp Neurol 66 (8):732–739. doi:10.1097/nen.0b013e31812571b0
114. Verkhratsky A, Nedergaard M (2014) Astroglial cradle in the life of the synapse. Philos Trans R Soc Lond B Biol Sci 369(1654):20130595. doi:10.1098/rstb.2013.0595
115. Bergles DE, Jahr CE (1997) Synaptic activation of glutamate transporters in hippocampal astrocytes. Neuron 19(6):1297–1308
116. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ (2012) Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci 13(7):465–477. doi:10.1038/nrn3257
117. Stone TW, Forrest CM, Darlington LG (2012) Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection. FEBS J 279(8):1386–1397. doi:10.1111/j.1742-4658.2012.08487.x
118. Vecsei L, Szalardy L, Fulop F, Toldi J (2013) Kynurenines in the CNS: recent advances and new questions. Nat Rev Drug Discov 12(1):64–82. doi:10.1038/nrd3793
119. Schwarcz R, Pellicciari R (2002) Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. J Pharmacol Exp Ther 303(1):1–10. doi:10.1124/jpet.102.034439
120. Schwarcz R (2016) Kynurenines and glutamate: multiple links and therapeutic implications. Adv Pharmacol 76:13–37. doi:10.1016/bs.apha.2016.01.005
121. Guillemin GJ (2012) Quinolinic acid: neurotoxicity. FEBS J 279(8):1355. doi:10.1111/j.1742-4658.2012.08493.x
122. Schwarcz R (2004) The kynurenine pathway of tryptophan degradation as a drug target. Curr Opin Pharmacol 4(1):12–17. doi:10.1016/j.coph.2003.10.006
123. Brundin L, Erhardt S, Bryleva EY, Achtyes ED, Postolache TT (2015) The role of inflammation in suicidal behaviour. Acta Psychiatr Scand 132(3):192–203. doi:10.1111/acps.12458
124. Erhardt S, Lim CK, Linderholm KR, Janelidze S, Lindqvist D, Samuelsson M, Lundberg K, Postolache TT, Traskman-Bendz L, Guillemin GJ, Brundin L (2013) Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology 38(5):743–752. doi:10.1038/npp.2012.248
125. Raison CL, Dantzer R, Kelley KW, Lawson MA, Woolwine BJ, Vogt G, Spivey JR, Saito K, Miller AH (2010) CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Mol Psychiatry 15(4):393–403. doi:10.1038/mp.2009.116
126. Meier TB, Drevets WC, Wurfel BE, Ford BN, Morris HM, Victor TA, Bodurka J, Teague TK, Dantzer R, Savitz J (2016) Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder. Brain Behav Immun 53:39–48. doi:10.1016/j.bbi.2015.11.003
127. Savitz J, Dantzer R, Meier TB, Wurfel BE, Victor TA, McIntosh SA, Ford BN, Morris HM, Bodurka J, Teague TK, Drevets WC (2015) Activation of the kynurenine pathway is associated with striatal volume in major depressive disorder. Psychoneuroendocrinology 62:54–58. doi:10.1016/j.psyneuen.2015.07.609
128. Savitz J, Dantzer R, Wurfel BE, Victor TA, Ford BN, Bodurka J, Bellgowan PS, Teague TK, Drevets WC (2015) Neuroprotective kynurenine metabolite indices are abnormally reduced and positively associated with hippocampal and amygdalar volume in bipolar disorder. Psychoneuroendocrinology 52:200–211. doi:10.1016/j.psyneuen.2014.11.015
129. Savitz J, Drevets WC, Smith CM, Victor TA, Wurfel BE, Bellgowan PS, Bodurka J, Teague TK, Dantzer R (2015c) Putative neuroprotective and neurotoxic kynurenine pathway metabolites are associated with hippocampal and amygdalar volumes in subjects with major depressive disorder. Neuropsychopharmacology 40(2):463–471. doi:10.1038/npp.2014.194
130. Walker AJ, Foley BM, Sutor SL, McGillivray JA, Frye MA, Tye SJ (2015) Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance. Behav Brain Res 293:198–202. doi:10.1016/j.bbr.2015.07.026
131. Yang JJ, Wang N, Yang C, Shi JY, HY Y, Hashimoto K (2015) Serum interleukin-6 is a predictive biomarker for ketamine’s antidepressant effect in treatment-resistant patients with major depression. Biol Psychiatry 77(3):e19–e20. doi:10.1016/j.biopsych.2014.06.021
132. Machado-Vieira R, Gold PW, Luckenbaugh DA, Ballard ED, Richards EM, Henter ID, De Sousa RT, Niciu MJ, Yuan P, Zarate CA Jr. (2016) The role of adipokines in the rapid antidepressant effects of ketamine. Mol Psychiatry. doi:10.1038/mp.2016.36
133. Haroon E, Woolwine BJ, Chen X, Pace TW, Parekh S, Spivey JR, XP H, Miller AH (2014) IFN-alpha-induced cortical and subcortical glutamate changes assessed by magnetic resonance spectroscopy. Neuropsychopharmacology 39(7):1777–1785. doi:10.1038/npp.2014.25
134. Capuron L, Pagnoni G, Demetrashvili M, Woolwine BJ, Nemeroff CB, Berns GS, Miller AH (2005) Anterior cingulate activation and error processing during interferon-alpha treatment. Biol Psychiatry 58(3):190–196
135. Capuron L, Pagnoni G, Demetrashvili MF, Lawson DH, Fornwalt FB, Woolwine B, Berns GS, Nemeroff CB, Miller AH (2007) Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy. Neuropsychopharmacology 32(11):2384–2392. doi:10.1038/sj.npp.1301362
136. Capuron L, Pagnoni G, Drake D, Woolwine B, Spivey J, Crowe R, Votaw J, Goodman M, Miller A (2012) Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration. Arch Gen Psychiatry 69(10):1044–1053. doi:10.1001/archgenpsychiatry.2011.2094
137. Harrison NA, Voon V, Cercignani M, Cooper EA, Pessiglione M, Critchley HD (2015) A Neurocomputational account of how inflammation enhances sensitivity to punishments versus rewards. Biol Psychiatry. doi:10.1016/j.biopsych.2015.07.018
138. Slavich GM, Way BM, Eisenberger NI, Taylor SE (2010) Neural sensitivity to social rejection is associated with inflammatory responses to social stress. Proc Natl Acad Sci U S A 107(33):14817–14822. doi:10.1073/pnas.1009164107
139. Godbout J, Johnson R (2009) Age and neuroinflammation: a lifetime of psychoneuroimmune consequences. Immunol Allergy Clin North Am 29(2):321–337. doi:10.1016/j.iac.2009.02.007
140. Haroon E, Felger JC, Woolwine BJ, Chen X, Parekh S, Spivey JR, XP H, Miller AH (2015) Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: preliminary findings. Brain Behav Immun 46:17–22. doi:10.1016/j.bbi.2014.12.004