Targeting the NMDA receptor subunit NR2B for treating or preventing age-related memory decline

Expert Opinion on Therapeutic Targets

Volumn 18, Issue 10, 2014, Pages 1121-1130

  Wang, Deheng ^a   Jacobs, Stephanie A ^b   Tsien, Joe Z ^b  

^a Banna Biomedical Research Institute   (China)

^b MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

Age related memory loss; Alzheimer; Depression; Magnesium; Magnesium L threonate; Memory enhancement; Mild cognitive impairment; NMDA receptor NR2B; NMDA receptors; Parkinson; Schizophrenia

Indexed keywords

CYCLIN DEPENDENT KINASE 5; MAGNESIUM; MAGNESIUM SULFATE; MAGNESIUM THREONATE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG; BUTYRIC ACID DERIVATIVE; NR2B NMDA RECEPTOR; THREONIC ACID;

AGE RELATED MEMORY LOSS; DEGENERATIVE DISEASE; DIET SUPPLEMENTATION; LEARNING; LONG TERM CARE; MEMORY DISORDER; MOLECULAR MECHANICS; NERVE CELL PLASTICITY; NONHUMAN; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SPATIAL MEMORY; UPREGULATION; WORKING MEMORY; AGING; ANIMAL; BRAIN; COGNITION; DRUG EFFECTS; GENETICS; HUMAN; MEMORY; MEMORY DISORDERS; METABOLISM; MOLECULARLY TARGETED THERAPY; PHYSIOLOGY;

AGING; ANIMALS; BRAIN; BUTYRATES; COGNITION; DIETARY SUPPLEMENTS; HUMANS; MAGNESIUM; MEMORY; MEMORY DISORDERS; MOLECULAR TARGETED THERAPY; NEURONAL PLASTICITY; RECEPTORS, N-METHYL-D-ASPARTATE; UP-REGULATION;

EID: 84907062342     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2014.941286     Document Type: Review

References (100)

1. Hebb D. The organization of behavior John Wiley New York; 1949. Hebb D. The organization of behavior John Wiley, New York; 1949.
2. Morris RG, Anderson E, Lynch GS, Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 1986;319(6056):774-6
3. Sakimura K, Kutsuwada T, Ito I, et al. Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon 1 subunit. Nature 1995;373(6510):151-5
4. Tsien JZ, Huerta PT, Tonegawa S. The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. Cell 1996;87(7):1327-38 .
5. Nakazawa K, Quirk MC, Chitwood RA, et al. Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 2002;297(5579):211-18
6. Nakazawa K, Sun LD, Quirk MC, et al. Hippocampal CA3 NMDA receptors are crucial for memory acquisition of onetime experience. Neuron 2003;38(2):305-15
7. Zhang H, Chen G, Kuang H, Tsien JZ. Mapping and deciphering neural codes of NMDA receptor-dependent fear memory engrams in the hippocampus. PLoS One 2013;8(11):e79454 .
8. Cui Z, Feng R, Jacobs S, et al. Increased NR2A:NR2B ratio compresses long-term depression range and constrains longterm memory. Sci Rep 2013;3:1036.
9. Monyer H, Burnashev N, Laurie DJ, et al. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994;12(3):529-40
10. Sheng M, Cummings J, Roldan LA, et al. Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 1994;368(6467):144-7
11. Slutsky I, Sadeghpour S, Li B, Liu G. Enhancement of synaptic plasticity through chronically reduced Ca2+ flux during uncorrelated activity. Neuron 2004;44(5):835-49 .
12. Li W, Yu J, Liu Y, et al. Elevation of brain magnesium prevents and reverses cognitive deficits and synaptic loss in Alzheimer's disease mouse model. J Neurosci 2013;33(19):8423-41
13. Slutsky I, Abumaria N, Wu LJ, et al. Enhancement of learning and memory by elevating brain magnesium. Neuron 2010;65(2):165-77 .
14. Corlew R, Wang Y, Ghermazien H, et al. Developmental switch in the contribution of presynaptic and postsynaptic NMDA receptors to longterm depression. J Neurosci 2007;27(37):9835-45
15. Rodriguez-Moreno A, Kohl MM, Reeve JE, et al. Presynaptic induction and expression of timing-dependent longterm depression demonstrated by compartment-specific photorelease of a use-dependent NMDA receptor antagonist. J Neurosci 2011;31(23):8564-9
16. Farrant M, Feldmeyer D, Takahashi T, Cull-Candy SG. NMDA-receptor channel diversity in the developing cerebellum. Nature 1994;368(6469):335-9
17. Wenzel A, Fritschy JM, Mohler H, Benke D. NMDA receptor heterogeneity during postnatal development of the rat brain: differential expression of the NR2A, NR2B, and NR2C subunit proteins. J Neurochem 1997;68(2):469-78
18. Karavanova I, Vasudevan K, Cheng J, Buonanno A. Novel regional and developmental NMDA receptor expression patterns uncovered in NR2C subunit-beta-galactosidase knock-in mice. Mol Cell Neurosci 2007;34(3):468-80
19. Magnusson KR. Declines in mRNA expression of different subunits may account for differential effects of aging on agonist and antagonist binding to the NMDA receptor. J Neurosci 2000;20(5):1666-74
20. Laurie DJ, Bartke I, Schoepfer R, et al. Regional, developmental and interspecies expression of the four NMDAR2 subunits, examined using monoclonal antibodies. Brain Res Mol Brain Res 1997;51(1-2):23-32
21. Watanabe M, Inoue Y, Sakimura K, Mishina M. Developmental changes in distribution of NMDA receptor channel subunit mRNAs. Neuroreport 1992;3(12):1138-40
22. Hrabetova S, Serrano P, Blace N, et al. Distinct NMDA receptor subpopulations contribute to long-term potentiation and long-term depression induction. J Neurosci 2000;20(12):RC81
23. Tang YP, Shimizu E, Dube GR, et al. Genetic enhancement of learning and memory in mice. Nature 1999;401(6748):63-9
24. Wang D, Cui Z, Zeng Q, et al. Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats. PLoS One 2009;4(10):e7486 .
25. Kennedy MB. Signal-processing machines at the postsynaptic density. Science 2000;290(5492):750-4
26. Sheng M, Pak DT. Ligand-gated ion channel interactions with cytoskeletal and signaling proteins. Annu Rev Physiol 2000;62:755-78
27. Garner CC, Nash J, Huganir RL. PDZ domains in synapse assembly and signalling. Trends Cell Biol 2000;10(7):274-80
28. Erondu NE, Kennedy MB. Regional distribution of type II Ca2+/calmodulindependent protein kinase in rat brain. J Neurosci 1985;5(12):3270-7
29. Lisman J, Schulman H, Cline H. The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci 2002;3(3):175-90
30. Bayer KU, De Koninck P, Leonard AS, et al. Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature 2001;411(6839):801-5
31. Cruz JC, Tsai LH. A Jekyll and Hyde kinase: roles for Cdk5 in brain development and disease. Curr Opin Neurobiol 2004;14(3):390-4
32. Cicero S, Herrup K. Cyclin-dependent kinase 5 is essential for neuronal cell cycle arrest and differentiation. J Neurosci 2005;25(42):9658-68
33. Chae T, Kwon YT, Bronson R, et al. Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 1997;18(1):29-42
34. Angelo M, Plattner F, Giese KP. Cyclin-dependent kinase 5 in synaptic plasticity, learning and memory. J Neurochem 2006;99(2):353-70
35. Brambilla R, Gnesutta N, Minichiello L, et al. A role for the Ras signalling pathway in synaptic transmission and long-term memory. Nature 1997;390(6657):281-6
36. Zhu JJ, Qin Y, Zhao M, et al. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 2002;110(4):443-55
37. Silva AJ, Frankland PW, Marowitz Z, et al. A mouse model for the learning and memory deficits associated with neurofibromatosis type I. Nat Genet 1997;15(3):281-4
38. Magnusson KR. Aging of the NMDA receptor: from a mouse's point of view. Fut Neurol 2012;7(5):627-37 .
39. Cao X, Cui Z, Feng R, et al. Maintenance of superior learning and memory function in NR2B transgenic mice during ageing. Eur J Neurosci 2007;25(6):1815-22 .
40. Rampon C, Jiang CH, Dong H, et al. Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci USA 2000. 97(23):12880-4 .
41. Brim BL, Haskell R, Awedikian R, et al. Memory in aged mice is rescued by enhanced expression of the GluN2B subunit of the NMDA receptor. Behav Brain Res 2013;238:211-26
42. Burke SN, Barnes CA. Neural plasticity in the ageing brain. Nat Rev Neurosci 2006;7(1):30-40
43. Vicario-Abejon C, Owens D, McKay R, Segal M. Role of neurotrophins in central synapse formation and stabilization. Nat Rev Neurosci 2002;3(12):965-74
44. Diano S, Farr SA, Benoit SC, et al. Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci 2006;9(3):381-8
45. Wu LJ, Zhang XH, Fukushima H, et al. Genetic enhancement of trace fear memory and cingulate potentiation in mice overexpressing Ca2+/calmodulindependent protein kinase IV. Eur J Neurosci 2008;27(8):1923-32
46. Fukushima H, Maeda R, Suzuki R, et al. Upregulation of calcium/calmodulindependent protein kinase IV improves memory formation and rescues memory loss with aging. J Neurosci 2008;28(40):9910-19
47. Li C, Brake WG, Romeo RD, et al. Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice. Proc Natl Acad Sci USA 2004;101(7):2185-90
48. Lichtenwalner RJ, Forbes ME, Bennett SA, et al. Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 2001;107(4):603-13
49. O'Kusky JR, Ye P, D'Ercole AJ. Insulin-like growth factor-I promotes neurogenesis and synaptogenesis in the hippocampal dentate gyrus during postnatal development. J Neurosci 2000;20(22):8435-42
50. Plattner F, Hernandez A, Kistler TM, et al. Memory Enhancement by Targeting Cdk5 Regulation of NR2B. Neuron 2014;81(5):1070-83 .
51. Hawasli AH, Benavides DR, Nguyen C, et al. Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation. Nat Neurosci 2007;10(7):880-6
52. Yin X, Takei Y, Kido MA, Hirokawa N. Molecular motor KIF17 is fundamental for memory and learning via differential support of synaptic NR2A/2B levels. Neuron 2011;70(2):310-25
53. Yin X, Feng X, Takei Y, Hirokawa N. Regulation of NMDA receptor transport: a KIF17-cargo binding/releasing underlies synaptic plasticity and memory in vivo. J Neurosci 2012;32(16):5486-99
54. Wong RW, Setou M, Teng J, et al. Overexpression of motor protein KIF17 enhances spatial and working memory in transgenic mice. Proc Natl Acad Sci USA 2002;99(22):14500-5 .
55. Bustos G, Abarca J, Campusano J, et al. Functional interactions between somatodendritic dopamine release, glutamate receptors and brain-derived neurotrophic factor expression in mesencephalic structures of the brain. Brain Res Brain Res Rev 2004;47(1-3):126-44
56. Bustos G, Abarca J, Bustos V, et al. NMDA receptors mediate an early upregulation of brain-derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's disease. J Neurosci Res 2009;87(10):2308-18
57. Jang SW, Liu X, Yepes M, et al. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl Acad Sci USA 2010;107(6):2687-92
58. Mandel SA, Sagi Y, Amit T. Rasagiline promotes regeneration of substantia nigra dopaminergic neurons in post-MPTP-induced Parkinsonism via activation of tyrosine kinase receptor signaling pathway. Neurochem Res 2007;32(10):1694-9
59. Riquelme E, Abarca J, Campusano JM, Bustos G. An NR2B-dependent decrease in the expression of trkB receptors precedes the disappearance of dopaminergic cells in substantia nigra in a rat model of presymptomatic Parkinson's disease. Parkinsons Dis 2012;2012:129605
60. Blanchet PJ, Papa SM, Metman LV, et al. Modulation of levodopa-induced motor response complications by NMDA antagonists in Parkinson's disease. Neurosci Biobehav Rev 1997;21(4):447-53
61. Bibbiani F, Oh JD, Kielaite A, et al. Combined blockade of AMPA and NMDA glutamate receptors reduces levodopa-induced motor complications in animal models of PD. Exp Neurol 2005;196(2):422-9
62. Chase TN, Oh JD, Konitsiotis S. Antiparkinsonian and antidyskinetic activity of drugs targeting central glutamatergic mechanisms. J Neurol 2000;247(Suppl 2):II36-42
63. Papa SM, Boldry RC, Engber TM, et al. Reversal of levodopa-induced motor fluctuations in experimental parkinsonism by NMDA receptor blockade. Brain Res 1995;701(1-2):13-18
64. Engber TM, Papa SM, Boldry RC, Chase TN. NMDA receptor blockade reverses motor response alterations induced by levodopa. Neuroreport 1994;5(18):2586-8
65. Marin C, Papa S, Engber TM, et al. MK-801 prevents levodopa-induced motor response alterations in parkinsonian rats. Brain Res 1996;736(1-2):202-5
66. Dunah AW, Wang Y, Yasuda RP, et al. Alterations in subunit expression, composition, and phosphorylation of striatal N-methyl-D-aspartate glutamate receptors in a rat 6-hydroxydopamine model of Parkinson's disease. Mol Pharmacol 2000;57(2):342-52
67. Hutton M, Hardy J. The presenilins and Alzheimer's disease. Hum Mol Genet 1997;6(10):1639-46
68. Saura CA, Choi SY, Beglopoulos V, et al. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 2004;42(1):23-36
69. Shen J, Kelleher RJ III. The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci USA 2007;104(2):403-9
70. Sze C, Bi H, Kleinschmidt-DeMasters BK, et al. Nmethyl-D-aspartate receptor subunit proteins and their phosphorylation status are altered selectively in Alzheimer's disease. J Neurol Sci 2001;182(2):151-9
71. Kornhuber J, Bormann J, Retz W, et al. Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur J Pharmacol 1989;166(3):589-90
72. Chen HS, Pellegrini JW, Aggarwal SK, et al. Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J Neurosci 1992;12(11):4427-36
73. Chen HS, Lipton SA. Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism. J Physiol 1997;499(Pt 1):27-46
74. Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev 2003;9(3):275-308
75. Robinson DM, Keating GM. Memantine: a review of its use in Alzheimer's disease. Drugs 2006;66(11):1515-34
76. Areosa SA, Sherriff F, McShane R. Memantine for dementia. Cochrane Database Syst Rev 2005(3):CD003154
77. Cacabelos R, Takeda M, Winblad B. The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease. Int J Geriatr Psychiatry 1999;14(1):3-47
78. Mayer ML, Westbrook GL, Guthrie PB. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 1984;309(5965):261-3
79. Nowak L, Bregestovski P, Ascher P, et al. Magnesium gates glutamate-activated channels in mouse central neurones. Nature 1984;307(5950):462-5
80. Cyranoski D. Testing magnesium's brain-boosting effects. Nature News 2012
81. Dribben WH, Eisenman LN, Mennerick S. Magnesium induces neuronal apoptosis by suppressing excitability. Cell Death Dis 2010;1:e63
82. Hashimoto T, Nishi K, Nagasao J, et al. Magnesium exerts both preventive and ameliorating effects in an in vitro rat Parkinson disease model involving 1-methyl-4-phenylpyridinium (MPP+) toxicity in dopaminergic neurons. Brain Res 2008;1197:143-51
83. Vennemeyer J, Hopkins T, Kuhlmann J, et al. Effects of elevated magnesium and substrate on neuronal numbers and neurite outgrowth of neural stem/progenitor cells in vitro. Neurosci Res 2014; S0168-0102(14)00074-1
84. Du J, Zhou S, Coggeshall RE, Carlton SM. N-methyl-D-aspartateinduced excitation and sensitization of normal and inflamed nociceptors. Neuroscience 2003;118(2):547-62
85. Suzuki R, Matthews EA, Dickenson AH. Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy. Pain 2001;91(1-2):101-9
86. Danysz W, Parsons CG. Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications. Pharmacol Rev 1998;50(4):597-664
87. Wei F, Wang GD, Kerchner GA, et al. Genetic enhancement of inflammatory pain by forebrain NR2B overexpression. Nat Neurosci 2001;4(2):164-9
88. Tan PH, Yang LC, Shih HC, et al. Gene knockdown with intrathecal siRNA of NMDA receptor NR2B subunit reduces formalin-induced nociception in the rat. Gene Ther 2005;12(1):59-66
89. Chizh BA, Headley PM, Tzschentke TM. NMDA receptor antagonists as analgesics: focus on the NR2B subtype. Trends Pharmacol Sci 2001;22(12):636-42
90. Tang Y, Shimizu E, Tsien JZ. Do 'smart' mice feel more pain, or are they just better learners? Nat Neurosci 2001;4(5):453-4
91. Wang J, Liu Y, Zhou LJ, et al. Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-alpha. Pain Physician 2013;16(5):E563-75
92. Tsien JZ. Linking Hebb's coincidencedetection to memory formation. Curr Opin Neurobiol 2000;10(2):266-73
93. Cui Y, Jin J, Zhang X, et al. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice. PLoS One 2011;6(5):e20312 .
94. Jacobs SA, Tsien JZ. Genetic overexpression of NR2B subunit enhances social recognition memory for different strains and species. PLoS One 2012;7(4):e36387 .
95. White TL, Youngentob SL. The effect of NMDA-NR2B receptor subunit overexpression on olfactory memory task performance in the mouse. Brain Res 2004;1021(1):1-7 .
96. Bibb JA, Mayford MR, Tsien JZ, Alberini CM. Cognition enhancement strategies. J Neurosci 2010;30(45):14987-92
97. Abumaria N, Luo L, Ahn M, Liu G. Magnesium supplement enhances spatialcontext pattern separation and prevents fear overgeneralization. Behav Pharmacol 2013;24(4):255-63
98. Mickley GA, Hoxha N, Luchsinger JL, et al. Chronic dietary magnesium-L-threonate speeds extinction and reduces spontaneous recovery of a conditioned taste aversion. Pharmacol Biochem Behav 2013;106:16-26
99. Abumaria N, Yin B, Zhang L, et al. Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala. J Neurosci 2011;31(42):14871-81
100. Mickley GA, Hoxha N, Luchsinger JL, et al. Chronic dietary magnesium-L-threonate speeds extinction and reduces spontaneous recovery of a conditioned taste aversion. Pharmacol Biochem Behav 2013;106:16-26