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Age and Alzheimer’s disease gene expression profiles reversed by the glutamate modulator riluzole

Abstract

Alzheimer’s disease (AD) and age-related cognitive decline represent a growing health burden and involve the hippocampus, a vulnerable brain region implicated in learning and memory. To understand the molecular effects of aging on the hippocampus, this study characterized the gene expression changes associated with aging in rodents using RNA-sequencing (RNA-seq). The glutamate modulator, riluzole, which was recently shown to improve memory performance in aged rats, prevented many of the hippocampal age-related gene expression changes. A comparison of the effects of riluzole in rats against human AD data sets revealed that many of the gene changes in AD are reversed by riluzole. Expression changes identified by RNA-Seq were validated by qRT–PCR open arrays. Riluzole is known to increase the glutamate transporter EAAT2’s ability to scavenge excess glutamate, regulating synaptic transmission. RNA-seq and immunohistochemistry confirmed an increase in EAAT2 expression in hippocampus, identifying a possible mechanism underlying the improved memory function after riluzole treatment.

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References

  1. 1

    Buckner RL . Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron 2004; 44: 195–208.

    CAS  Google Scholar 

  2. 2

    Burke SN, Barnes CA . Neural plasticity in the ageing brain. Nat Rev Neurosci 2006; 7: 30–40.

    CAS  Google Scholar 

  3. 3

    Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM . Forecasting the global burden of Alzheimer's disease. Alzheimers Dement 2007; 3: 186–191.

    Google Scholar 

  4. 4

    Morrison JH, Hof PR . Life and death of neurons in the aging brain. Science 1997; 278: 412–419.

    CAS  Google Scholar 

  5. 5

    Morrison JH, Hof PR . Selective vulnerability of corticocortical and hippocampal circuits in aging and Alzheimer's disease. Prog Brain Res 2002; 136: 467–486.

    CAS  Google Scholar 

  6. 6

    Neves G, Cooke SF, Bliss TV . Synaptic plasticity, memory and the hippocampus: a neural network approach to causality. Nat Rev Neurosci 2008; 9: 65–75.

    CAS  Google Scholar 

  7. 7

    Braak H, Braak E . Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82: 239–259.

    CAS  Google Scholar 

  8. 8

    Bensimon G, Lacomblez L, Meininger V . A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med 1994; 330: 585–591.

    CAS  Google Scholar 

  9. 9

    Pereira AC, Lambert HK, Grossman YS, Dumitriu D, Waldman R, Jannetty SK et al. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering. Proc Natl Acad Sci USA 2014; 111: 18733–18738.

    CAS  Google Scholar 

  10. 10

    Grutzendler J, Kasthuri N, Gan WB . Long-term dendritic spine stability in the adult cortex. Nature 2002; 420: 812–816.

    CAS  Google Scholar 

  11. 11

    Larkum ME, Nevian T . Synaptic clustering by dendritic signalling mechanisms. Curr Opin Neurobiol 2008; 18: 321–331.

    CAS  Google Scholar 

  12. 12

    Polsky A, Mel BW, Schiller J . Computational subunits in thin dendrites of pyramidal cells. Nat Neurosci 2004; 7: 621–627.

    CAS  Google Scholar 

  13. 13

    Kavalali ET, Klingauf J, Tsien RW . Activity-dependent regulation of synaptic clustering in a hippocampal culture system. Proc Natl Acad Sci USA 1999; 96: 12893–12900.

    CAS  Google Scholar 

  14. 14

    Kleindienst T, Winnubst J, Roth-Alpermann C, Bonhoeffer T, Lohmann C . Activity-dependent clustering of functional synaptic inputs on developing hippocampal dendrites. Neuron 2011; 72: 1012–1024.

    CAS  Google Scholar 

  15. 15

    De Roo M, Klauser P, Muller D . LTP promotes a selective long-term stabilization and clustering of dendritic spines. PLoS Biol 2008; 6: e219.

    PubMed  PubMed Central  Google Scholar 

  16. 16

    Hardingham GE . Pro-survival signalling from the NMDA receptor. Biochem Soc Trans 2006; 34: 936–938.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Hardingham GE, Bading H . Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci 2010; 11: 682–696.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Rusakov DA, Kullmann DM . Extrasynaptic glutamate diffusion in the hippocampus: ultrastructural constraints, uptake, and receptor activation. J Neurosci 1998; 18: 3158–3170.

    CAS  Google Scholar 

  19. 19

    Furuta A, Rothstein JD, Martin LJ . Glutamate transporter protein subtypes are expressed differentially during rat CNS development. J Neurosci 1997; 17: 8363–8375.

    CAS  Google Scholar 

  20. 20

    Tzingounis AV, Wadiche JI . Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat Rev Neurosci 2007; 8: 935–947.

    CAS  Google Scholar 

  21. 21

    Potier B, Billard JM, Riviere S, Sinet PM, Denis I, Champeil-Potokar G et al. Reduction in glutamate uptake is associated with extrasynaptic NMDA and metabotropic glutamate receptor activation at the hippocampal CA1 synapse of aged rats. Aging Cell 2010; 9: 722–735.

    CAS  Google Scholar 

  22. 22

    Brothers HM, Bardou I, Hopp SC, Kaercher RM, Corona AW, Fenn AM et al. Riluzole partially rescues age-associated, but not LPS-induced, loss of glutamate transporters and spatial memory. J Neuroimmune Pharmacol 2013; 8: 1098–1105.

    Google Scholar 

  23. 23

    Jacob CP, Koutsilieri E, Bartl J, Neuen-Jacob E, Arzberger T, Zander N et al. Alterations in expression of glutamatergic transporters and receptors in sporadic Alzheimer's disease. J Alzheimers Dis 2007; 11: 97–116.

    CAS  Google Scholar 

  24. 24

    Masliah E, Alford M, DeTeresa R, Mallory M, Hansen L . Deficient glutamate transport is associated with neurodegeneration in Alzheimer's disease. Ann Neurol 1996; 40: 759–766.

    CAS  Google Scholar 

  25. 25

    Huang YH, Bergles DE . Glutamate transporters bring competition to the synapse. Curr Opin Neurobiol 2004; 14: 346–352.

    CAS  Google Scholar 

  26. 26

    Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL et al. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol Psychiatry 2010; 15: 501–511.

    CAS  Google Scholar 

  27. 27

    Hunsberger HC, Weitzner DS, Rudy CC, Hickman JE, Libell EM, Speer RR et al. Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression. J Neurochem 2015; 135: 381–394.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Gourley SL, Espitia JW, Sanacora G, Taylor JR . Antidepressant-like properties of oral riluzole and utility of incentive disengagement models of depression in mice. Psychopharmacology 2012; 219: 805–814.

    CAS  Google Scholar 

  29. 29

    Frizzo ME, Dall'Onder LP, Dalcin KB, Souza DO . Riluzole enhances glutamate uptake in rat astrocyte cultures. Cell Mol Neurobiol 2004; 24: 123–128.

    CAS  Google Scholar 

  30. 30

    Fumagalli E, Funicello M, Rauen T, Gobbi M, Mennini T . Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1. Eur J Pharmacol 2008; 578: 171–176.

    CAS  Google Scholar 

  31. 31

    Faherty SL, Campbell CR, Larsen PA, Yoder AD . Evaluating whole transcriptome amplification for gene profiling experiments using RNA-Seq. BMC Biotechnol 2015; 15: 65.

    PubMed  PubMed Central  Google Scholar 

  32. 32

    Maag JL, Panja D, Sporild I, Patil S, Kaczorowski DC, Bramham CR et al. Dynamic expression of long noncoding RNAs and repeat elements in synaptic plasticity. Front Neurosci 2015; 9: 351.

    PubMed  PubMed Central  Google Scholar 

  33. 33

    Gray JD, Rubin TG, Hunter RG, McEwen BS . Hippocampal gene expression changes underlying stress sensitization and recovery. Mol Psychiatry 2014; 19: 1171–1178.

    CAS  Google Scholar 

  34. 34

    Goecks J, Nekrutenko A, Taylor J . Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. Genome Biol 2010; 11: R86.

    PubMed  PubMed Central  Google Scholar 

  35. 35

    Blankenberg D, Von Kuster G, Coraor N, Ananda G, Lazarus R, Mangan M et al. Galaxy: a web-based genome analysis tool for experimentalists. Curr Protoc Mol Biol 2010; Chapter 19: 11–21.

    Google Scholar 

  36. 36

    Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL . TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 2013; 14: R36.

    PubMed  PubMed Central  Google Scholar 

  37. 37

    Livak KJ, Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402–408.

    CAS  PubMed  Google Scholar 

  38. 38

    Hokama M, Oka S, Leon J, Ninomiya T, Honda H, Sasaki K et al. Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study. Cereb Cortex 2014; 24: 2476–2488.

    Google Scholar 

  39. 39

    Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Walker DG et al. Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol Genomics 2007; 28: 311–322.

    CAS  Google Scholar 

  40. 40

    Berchtold NC, Coleman PD, Cribbs DH, Rogers J, Gillen DL, Cotman CW . Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer's disease. Neurobiol Aging 2013; 34: 1653–1661.

    CAS  Google Scholar 

  41. 41

    Silva AR, Grinberg LT, Farfel JM, Diniz BS, Lima LA, Silva PJ et al. Transcriptional alterations related to neuropathology and clinical manifestation of Alzheimer's disease. PLoS One 2012; 7: e48751.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    Xu PT, Li YJ, Qin XJ, Kroner C, Green-Odlum A, Xu H et al. A SAGE study of apolipoprotein E3/3, E3/4 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease. Mol Cell Neurosci 2007; 36: 313–331.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Miller JA, Woltjer RL, Goodenbour JM, Horvath S, Geschwind DH . Genes and pathways underlying regional and cell type changes in Alzheimer's disease. Genome Med 2013; 5: 48.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Blalock EM, Buechel HM, Popovic J, Geddes JW, Landfield PW . Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient Alzheimer's disease. J Chem Neuroanat 2011; 42: 118–126.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Small SA, Kent K, Pierce A, Leung C, Kang MS, Okada H et al. Model-guided microarray implicates the retromer complex in Alzheimer's disease. Ann Neurol 2005; 58: 909–919.

    CAS  Google Scholar 

  46. 46

    Kadish I, Thibault O, Blalock EM, Chen KC, Gant JC, Porter NM et al. Hippocampal and cognitive aging across the lifespan: a bioenergetic shift precedes and increased cholesterol trafficking parallels memory impairment. J Neurosci 2009; 29: 1805–1816.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

    Rowe WB, Blalock EM, Chen KC, Kadish I, Wang D, Barrett JE et al. Hippocampal expression analyses reveal selective association of immediate-early, neuroenergetic, and myelinogenic pathways with cognitive impairment in aged rats. J Neurosci 2007; 27: 3098–3110.

    CAS  Google Scholar 

  48. 48

    Cao X, Cui Z, Feng R, Tang YP, Qin Z, Mei B et al. Maintenance of superior learning and memory function in NR2B transgenic mice during ageing. Eur J Neurosci 2007; 25: 1815–1822.

    Google Scholar 

  49. 49

    Nayak TK, Sikdar SK . Time-dependent molecular memory in single voltage-gated sodium channel. J Membr Biol 2007; 219: 19–36.

    CAS  Google Scholar 

  50. 50

    Shen K, Teruel MN, Connor JH, Shenolikar S, Meyer T . Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II. Nat Neurosci 2000; 3: 881–886.

    CAS  Google Scholar 

  51. 51

    Glazewski S, Giese KP, Silva A, Fox K . The role of alpha-CaMKII autophosphorylation in neocortical experience-dependent plasticity. Nat Neurosci 2000; 3: 911–918.

    CAS  Google Scholar 

  52. 52

    Nothias F, Fischer I, Murray M, Mirman S, Vincent JD . Expression of a phosphorylated isoform of MAP1B is maintained in adult central nervous system areas that retain capacity for structural plasticity. J Comp Neurol 1996; 368: 317–334.

    CAS  Google Scholar 

  53. 53

    Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS, Roberts AC et al. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet 2011; 20: 3093–3108.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Dziembowska M, Wlodarczyk J . MMP9: a novel function in synaptic plasticity. Int J Biochem Cell Biol 2012; 44: 709–713.

    CAS  Google Scholar 

  55. 55

    Kim DH, Kim JM, Park SJ, Cai M, Liu X, Lee S et al. GABA(A) receptor blockade enhances memory consolidation by increasing hippocampal BDNF levels. Neuropsychopharmacology 2012; 37: 422–433.

    CAS  Google Scholar 

  56. 56

    Klein R, Nanduri V, Jing SA, Lamballe F, Tapley P, Bryant S et al. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell 1991; 66: 395–403.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57

    Massie A, Boillee S, Hewett S, Knackstedt L, Lewerenz J . Main path and byways: non-vesicular glutamate release by system x as an important modifier of glutamatergic neurotransmission. J Neurochem 2015; 135: 1062–1079.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Smith KR, Kopeikina KJ, Fawcett-Patel JM, Leaderbrand K, Gao R, Schurmann B et al. Psychiatric risk factor ANK3/ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses. Neuron 2014; 84: 399–415.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59

    Lisman J, Schulman H, Cline H . The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci 2002; 3: 175–190.

    CAS  Google Scholar 

  60. 60

    Thakker-Varia S, Alder J, Crozier RA, Plummer MR, Black IB . Rab3A is required for brain-derived neurotrophic factor-induced synaptic plasticity: transcriptional analysis at the population and single-cell levels. J Neurosci 2001; 21: 6782–6790.

    CAS  Google Scholar 

  61. 61

    Castillo PE, Janz R, Sudhof TC, Tzounopoulos T, Malenka RC, Nicoll RA . Rab3A is essential for mossy fibre long-term potentiation in the hippocampus. Nature 1997; 388: 590–593.

    CAS  Google Scholar 

  62. 62

    Asztely F, Erdemli G, Kullmann DM . Extrasynaptic glutamate spillover in the hippocampus: dependence on temperature and the role of active glutamate uptake. Neuron 1997; 18: 281–293.

    CAS  Google Scholar 

  63. 63

    Furness DN, Dehnes Y, Akhtar AQ, Rossi DJ, Hamann M, Grutle NJ et al. A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2). Neuroscience 2008; 157: 80–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Petr GT, Sun Y, Frederick NM, Zhou Y, Dhamne SC, Hameed MQ et al. Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes. J Neurosci 2015; 35: 5187–5201.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Chen W, Mahadomrongkul V, Berger UV, Bassan M, DeSilva T, Tanaka K et al. The glutamate transporter GLT1a is expressed in excitatory axon terminals of mature hippocampal neurons. J Neurosci 2004; 24: 1136–1148.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Danbolt NC, Storm-Mathisen J, Kanner BI . An [Na++K+]coupled L-glutamate transporter purified from rat brain is located in glial cell processes. Neuroscience 1992; 51: 295–310.

    CAS  Google Scholar 

  67. 67

    Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC . Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J Neurosci 1995; 15: 1835–1853.

    CAS  Google Scholar 

  68. 68

    Govindarajan A, Kelleher RJ, Tonegawa S . A clustered plasticity model of long-term memory engrams. Nat Rev Neurosci 2006; 7: 575–583.

    CAS  Google Scholar 

  69. 69

    Selkoe DJ . Alzheimer's disease is a synaptic failure. Science 2002; 298: 789–791.

    CAS  Google Scholar 

  70. 70

    DeKosky ST, Scheff SW . Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol 1990; 27: 457–464.

    CAS  Google Scholar 

  71. 71

    Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D . Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 2009; 62: 788–801.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Li S, Jin M, Koeglsperger T, Shepardson NE, Shankar GM, Selkoe DJ . Soluble Abeta oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci 2011; 31: 6627–6638.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Cheng L, Yin WJ, Zhang JF, Qi JS . Amyloid beta-protein fragments 25-35 and 31-35 potentiate long-term depression in hippocampal CA1 region of rats in vivo. Synapse 2009; 63: 206–214.

    CAS  Google Scholar 

  74. 74

    Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY et al. Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 2005; 8: 1051–1058.

    CAS  Google Scholar 

  75. 75

    Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T et al. APP processing and synaptic function. Neuron 2003; 37: 925–937.

    CAS  Google Scholar 

  76. 76

    Yamada K, Holth JK, Liao F, Stewart FR, Mahan TE, Jiang H et al. Neuronal activity regulates extracellular tau in vivo. J Exp Med 2014; 211: 387–393.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 77

    Pooler AM, Phillips EC, Lau DH, Noble W, Hanger DP . Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep 2013; 14: 389–394.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Sindou P, Lesort M, Couratier P, Yardin C, Esclaire F, Hugon J . Glutamate increases tau phosphorylation in primary neuronal cultures from fetal rat cerebral cortex. Brain Res 1994; 646: 124–128.

    CAS  Google Scholar 

  79. 79

    Esclaire F, Lesort M, Blanchard C, Hugon J . Glutamate toxicity enhances tau gene expression in neuronal cultures. J Neurosci Res 1997; 49: 309–318.

    CAS  Google Scholar 

  80. 80

    Mookherjee P, Green PS, Watson GS, Marques MA, Tanaka K, Meeker KD et al. GLT-1 loss accelerates cognitive deficit onset in an Alzheimer's disease animal model. J Alzheimers Dis 2011; 26: 447–455.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Takahashi K, Kong Q, Lin Y, Stouffer N, Schulte DA, Lai L et al. Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer's disease. J Exp Med 2015; 212: 319–332.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82

    Mennerick S, Zorumski CF . Glial contributions to excitatory neurotransmission in cultured hippocampal cells. Nature 1994; 368: 59–62.

    CAS  Google Scholar 

  83. 83

    Tong G, Jahr CE . Block of glutamate transporters potentiates postsynaptic excitation. Neuron 1994; 13: 1195–1203.

    CAS  Google Scholar 

  84. 84

    Murphy-Royal C, Dupuis JP, Varela JA, Panatier A, Pinson B, Baufreton J et al. Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission. Nat Neurosci 2015; 18: 219–226.

    CAS  Google Scholar 

  85. 85

    Chowdhury GM, Banasr M, de Graaf RA, Rothman DL, Behar KL, Sanacora G . Chronic riluzole treatment increases glucose metabolism in rat prefrontal cortex and hippocampus. J Cereb Blood Flow Metab 2008; 28: 1892–1897.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    Brennan BP, Hudson JI, Jensen JE, McCarthy J, Roberts JL, Prescot AP et al. Rapid enhancement of glutamatergic neurotransmission in bipolar depression following treatment with riluzole. Neuropsychopharmacology 2010; 35: 834–846.

    CAS  Google Scholar 

  87. 87

    Data obtained from the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) Target Discovery Consortium data portal and can be accessed at HYPERLINK. http://dx.doi.org/doi:10.7303/syn2580853; doi:10.7303/syn2580853.

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Acknowledgements

This work was supported by DANA Foundation, the Rockefeller University Women & Science Initiative and Alzheimer’s Drug Discovery Foundation to ACP, NIH grant F32 MH102065 to JDG, NIA grant R37 AG06647 to JHM and partial support by grant # UL1 TR000043 from the National Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS).

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Pereira, A., Gray, J., Kogan, J. et al. Age and Alzheimer’s disease gene expression profiles reversed by the glutamate modulator riluzole. Mol Psychiatry 22, 296–305 (2017). https://doi.org/10.1038/mp.2016.33

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