Activity-dependent alterations in the sensitivity to BDNF-TrkB signaling may promote excessive dendritic arborization and spinogenesis in fragile X syndrome in order to compensate for compromised postsynaptic activity

Medical Hypotheses

Volumn 83, Issue 4, 2014, Pages 429-435

  Kim, Sang Woo ^a   Cho, Kyoung Joo ^b  

^a BROWN UNIVERSITY   (United States)

^b Yonsei University College of Medicine   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR; ELONGATION FACTOR 2; METABOTROPIC RECEPTOR; MEMBRANE PROTEIN; PROTEIN TYROSINE KINASE; TROPOMYOSIN-RELATED KINASE-B, HUMAN;

ANIMAL MODEL; ARTICLE; CELL STRUCTURE; CELL SURVIVAL; CHANNELOPATHY; CONTROLLED STUDY; DENDRITE; ELECTRIC ACTIVITY; EXCITATORY POSTSYNAPTIC POTENTIAL; FRAGILE X SYNDROME; HUMAN; LONG TERM DEPRESSION; LONG TERM POTENTIATION; MOLECULAR SENSOR; MORPHOGENESIS; NERVE CELL; NONHUMAN; POSTSYNAPTIC DENSITY; RETT SYNDROME; SCHIZOPHRENIA; SIGNAL TRANSDUCTION; SPINE; SPINOCEREBELLAR TRACT; SPINOGENESIS; SYNAPSE; TUBEROUS SCLEROSIS; METABOLISM; PATHOLOGY;

ANIMALIA; EUKARYOTA;

BRAIN-DERIVED NEUROTROPHIC FACTOR; DENDRITES; FRAGILE X SYNDROME; HUMANS; MEMBRANE GLYCOPROTEINS; PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION; SYNAPSES;

EID: 84924023355     PISSN: 03069877     EISSN: 15322777     Source Type: Journal    
DOI: 10.1016/j.mehy.2014.07.007     Document Type: Article

References (148)

1. Bear M.F., Huber K.M., Warren S.T. The mGluR theory of fragile X mental retardation. Trends Neurosci 2004, 27(7):370-377.
2. Penagarikano O., Mulle J.G., Warren S.T. The pathophysiology of fragile x syndrome. Annu Rev Genomics Hum Genet 2007, 8:109-129.
3. Chiu S., et al. Early acceleration of head circumference in children with fragile x syndrome and autism. J Dev Behav Pediatr 2007, 28(1):31-35.
4. Dolen G., et al. Correction of fragile X syndrome in mice. Neuron 2007, 56(6):955-962.
5. Darnell J.C., et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 2011, 146(2):247-261.
6. Gladding C.M., Fitzjohn S.M., Molnar E. Metabotropic glutamate receptor-mediated long-term depression: molecular mechanisms. Pharmacol Rev 2009, 61(4):395-412.
7. Luscher C., Huber K.M. Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron 2010, 65(4):445-459.
8. Dolen G., Bear M.F. Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome. J Physiol 2008, 586(6):1503-1508.
9. Suvrathan A., et al. Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome. Proc Natl Acad Sci U S A 2010, 107(25):11591-11596.
10. Comery T.A., et al. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci U S A 1997, 94(10):5401-5404.
11. Irwin S.A., et al. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet 2001, 98(2):161-167.
12. Cheng C., Sourial M., Doering L.C. Astrocytes and developmental plasticity in fragile X. Neural Plast 2012, 2012:197491.
13. Gatto C.L., Broadie K. Temporal requirements of the fragile X mental retardation protein in the regulation of synaptic structure. Development 2008, 135(15):2637-2648.
14. Ivanco T.L., Greenough W.T. Altered mossy fiber distributions in adult Fmr1 (FVB) knockout mice. Hippocampus 2002, 12(1):47-54.
15. Muddashetty R.S., et al. Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. Mol Cell 2011, 42(5):673-688.
16. Pfeiffer B.E., et al. Fragile X mental retardation protein is required for synapse elimination by the activity-dependent transcription factor MEF2. Neuron 2010, 66(2):191-197.
17. Dolan B.M., et al. Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc Natl Acad Sci U S A 2013, 110(14):5671-5676.
18. Siller S.S., Broadie K. Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase. Dis Model Mech 2011, 4(5):673-685.
19. Lopez-Bucio J., et al. Phosphate availability alters architecture and causes changes in hormone sensitivity in the Arabidopsis root system. Plant Physiol 2002, 129(1):244-256.
20. Lopez-Bucio J., Cruz-Ramirez A., Herrera-Estrella L. The role of nutrient availability in regulating root architecture. Curr Opin Plant Biol 2003, 6(3):280-287.
21. Bostrom C.A., et al. Rescue of NMDAR-dependent synaptic plasticity in Fmr1 knock-out mice. Cereb Cortex 2013, [Epub ahead of print].
22. Eadie B.D., et al. NMDA receptor hypofunction in the dentate gyrus and impaired context discrimination in adult Fmr1 knockout mice. Hippocampus 2012, 22(2):241-254.
23. Meredith R.M., de Jong R., Mansvelder H.D. Functional rescue of excitatory synaptic transmission in the developing hippocampus in Fmr1-KO mouse. Neurobiol Dis 2011, 41(1):104-110.
24. Yun S.H., Trommer B.L. Fragile X mice: reduced long-term potentiation and N-Methyl-d-Aspartate receptor-mediated neurotransmission in dentate gyrus. J Neurosci Res 2011, 89(2):176-182.
25. Soontarapornchai K., et al. Abnormal nerve conduction features in fragile X premutation carriers. Arch Neurol 2008, 65(4):495-498.
26. Telias M., Segal M., Ben-Yosef D. Neural differentiation of Fragile X human Embryonic Stem Cells reveals abnormal patterns of development despite successful neurogenesis. Dev Biol 2013, 374(1):32-45.
27. Braun K., Segal M. FMRP involvement in formation of synapses among cultured hippocampal neurons. Cereb Cortex 2000, 10(10):1045-1052.
28. Linda L., Bambrick P.J.Y., Bruce K.KRUEGER Glutamate as a hippocampal neuron survival factor: an inherited defect in the trisomy 16 mouse. Proc Natl Acad Sci 1995, 92(21):9692-9696.
29. Schonfeld-Dado E., Segal M. Activity deprivation induces neuronal cell death: mediation by tissue-type plasminogen activator. PLoS One 2011, 6(10):e25919.
30. Bateup H.S., et al. Temporal dynamics of a homeostatic pathway controlling neural network activity. Front Mol Neurosci 2013, 6:28.
31. Zhao M.G., et al. Deficits in trace fear memory and long-term potentiation in a mouse model for fragile X syndrome. J Neurosci 2005, 25(32):7385-7392.
32. Lauterborn J.C., et al. Brain-derived neurotrophic factor rescues synaptic plasticity in a mouse model of fragile X syndrome. J Neurosci 2007, 27(40):10685-10694.
33. Mainen Z.F., Sejnowski T.J. Influence of dendritic structure on firing pattern in model neocortical neurons. Nature 1996, 382(6589):363-366.
34. Sepulveda F.J., et al. Differential roles of NMDA Receptor Subtypes NR2A and NR2B in dendritic branch development and requirement of RasGRF1. J Neurophysiol 2010, 103(4):1758-1770.
35. Xiong Q., et al. PTEN regulation of local and long-range connections in mouse auditory cortex. J Neurosci 2012, 32(5):1643-1652.
36. Gunnersen J.M., et al. Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons. Neuron 2007, 56(4):621-639.
37. Liu R.J., Aghajanian G.K. Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy. Proc Natl Acad Sci U S A 2008, 105(1):359-364.
38. Scheuss V., Bonhoeffer T. Function of Dendritic Spines on Hippocampal Inhibitory Neurons. Cereb Cortex 2013, [Epub ahead of print].
39. Gulledge A.T., Carnevale N.T., Stuart G.J. Electrical advantages of dendritic spines. PLoS One 2012, 7(4):e36007.
40. Srivastava D.P., Woolfrey K.M., Penzes P. Analysis of dendritic spine morphology in cultured CNS neurons. J Vis Exp 2011, 53:e2794.
41. Megias M., et al. Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells. Neuroscience 2001, 102(3):527-540.
42. Nagappan G., Lu B. Activity-dependent modulation of the BDNF receptor TrkB: mechanisms and implications. Trends Neurosci 2005, 28(9):464-471.
43. Tolwani R.J., et al. BDNF overexpression increases dendrite complexity in hippocampal dentate gyrus. Neuroscience 2002, 114(3):795-805.
44. Chapleau C.A., Pozzo-Miller L. Divergent roles of p75NTR and Trk receptors in BDNF's effects on dendritic spine density and morphology. Neural Plast 2012, 2012:578057.
45. Minichiello L. TrkB signalling pathways in LTP and learning. Nat Rev Neurosci 2009, 10(12):850-860.
46. Alonso M., Medina J.H., Pozzo-Miller L. ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons. Learn Mem 2004, 11(2):172-178.
47. Rocha M., Sur M. Rapid acquisition of dendritic spines by visual thalamic neurons after blockade of N-methyl-d-aspartate receptors. Proc Natl Acad Sci U S A 1995, 92(17):8026-8030.
48. Yuzaki M., et al. A stimulus paradigm inducing long-term desensitization of AMPA receptors evokes a specific increase in BDNF mRNA in cerebellar slices. Learn Mem 1994, 1(4):230-242.
49. Prithviraj R., Inglis F.M. Expression of the N-methyl-d-aspartate receptor subunit NR3B regulates dendrite morphogenesis in spinal motor neurons. Neuroscience 2008, 155(1):145-153.
50. Lee L.J., et al. Exuberant thalamocortical axon arborization in cortex-specific NMDAR1 knockout mice. J Comp Neurol 2005, 485(4):280-292.
51. Ni X., Martin-Caraballo M. Differential effect of glutamate receptor blockade on dendritic outgrowth in chicken lumbar motoneurons. Neuropharmacology 2010, 58(3):593-604.
52. Cohen-Cory S. BDNF modulates, but does not mediate, activity-dependent branching and remodeling of optic axon arbors in vivo. J Neurosci 1999, 19(22):9996-10003.
53. Nakayama K., Kiyosue K., Taguchi T. Diminished neuronal activity increases neuron-neuron connectivity underlying silent synapse formation and the rapid conversion of silent to functional synapses. J Neurosci 2005, 25(16):4040-4051.
54. Kirov S.A., Goddard C.A., Harris K.M. Age-dependence in the homeostatic upregulation of hippocampal dendritic spine number during blocked synaptic transmission. Neuropharmacology 2004, 47(5):640-648.
55. Lein E.S., et al. Subplate neuron ablation alters neurotrophin expression and ocular dominance column formation. Proc Natl Acad Sci U S A 1999, 96(23):13491-13495.
56. McAllister A.K., Katz L.C., Lo D.C. Neurotrophin regulation of cortical dendritic growth requires activity. Neuron 1996, 17(6):1057-1064.
57. Jakawich S.K., et al. Local presynaptic activity gates homeostatic changes in presynaptic function driven by dendritic BDNF synthesis. Neuron 2010, 68(6):1143-1158.
58. Hoy R.R., Nolen T.G., Casaday G.C. Dendritic sprouting and compensatory synaptogenesis in an identified interneuron follow auditory deprivation in a cricket. Proc Natl Acad Sci U S A 1985, 82(22):7772-7776.
59. Koyama R., et al. Brain-derived neurotrophic factor induces hyperexcitable reentrant circuits in the dentate gyrus. J Neurosci 2004, 24(33):7215-7224.
60. Murray P.S., Holmes P.V. An overview of brain-derived neurotrophic factor and implications for excitotoxic vulnerability in the hippocampus. Int J Pept 2011, 2011:654085.
61. Verpelli C., et al. Synaptic activity controls dendritic spine morphology by modulating eEF2-dependent BDNF synthesis. J Neurosci 2010, 30(17):5830-5842.
62. Cline H.T., Constantine-Paton M. NMDA receptor agonist and antagonists alter retinal ganglion cell arbor structure in the developing frog retinotectal projection. J Neurosci 1990, 10(4):1197-1216.
63. McAllister A.K. Cellular and molecular mechanisms of dendrite growth. Cereb Cortex 2000, 10(10):963-973.
64. Feldmeyer D., et al. Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B. Nat Neurosci 1999, 2(1):57-64.
65. Chang Q., et al. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 2006, 49(3):341-348.
66. + channel deficient mice. Neuroscience 2009, 163(1):73-81.
67. Gomes J.R., et al. Excitotoxicity downregulates TrkB.FL signaling and upregulates the neuroprotective truncated TrkB receptors in cultured hippocampal and striatal neurons. J Neurosci 2012, 32(13):4610-4622.
68. Cazorla M., et al. Striatal D2 receptors regulate dendritic morphology of medium spiny neurons via Kir2 channels. J Neurosci 2012, 32(7):2398-2409.
69. McCall T., et al. Depletion of polysialic acid from neural cell adhesion molecule (PSA-NCAM) increases CA3 dendritic arborization and increases vulnerability to excitotoxicity. Exp Neurol 2013, 241:5-12.
70. Hu P., Kalb R.G. BDNF heightens the sensitivity of motor neurons to excitotoxic insults through activation of TrkB. J Neurochem 2003, 84(6):1421-1430.
71. Pilpel Y., et al. Synaptic ionotropic glutamate receptors and plasticity are developmentally altered in the CA1 field of Fmr1 knockout mice. J Physiol 2009, 587(Pt 4):787-804.
72. Desai N.S., et al. Early postnatal plasticity in neocortex of Fmr1 knockout mice. J Neurophysiol 2006, 96(4):1734-1745.
73. Louhivuori V., et al. BDNF and TrkB in neuronal differentiation of Fmr1-knockout mouse. Neurobiol Dis 2011, 41(2):469-480.
74. Nimchinsky E.A., Oberlander A.M., Svoboda K. Abnormal development of dendritic spines in FMR1 knock-out mice. J Neurosci 2001, 21(14):5139-5146.
75. Portera-Cailliau C. Which comes first in fragile X syndrome, dendritic spine dysgenesis or defects in circuit plasticity?. Neuroscientist 2012, 18(1):28-44.
76. Jacobs S., Nathwani M., Doering L.C. Fragile X astrocytes induce developmental delays in dendrite maturation and synaptic protein expression. BMC Neurosci 2010, 11:132.
77. Jacobs S., Doering L.C. Astrocytes prevent abnormal neuronal development in the fragile x mouse. J Neurosci 2010, 30(12):4508-4514.
78. Gocel J., Larson J. Synaptic NMDA receptor-mediated currents in anterior piriform cortex are reduced in the adult fragile X mouse. Neuroscience 2012, 221:170-181.
79. Meredith R.M., et al. Increased threshold for spike-timing-dependent plasticity is caused by unreliable calcium signaling in mice lacking fragile X gene FMR1. Neuron 2007, 54(4):627-638.
80. Uutela M., et al. Reduction of BDNF expression in Fmr1 knockout mice worsens cognitive deficits but improves hyperactivity and sensorimotor deficits. Genes Brain Behav 2012, 11(5):513-523.
81. Irwin S.A., et al. Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice. Am J Med Genet 2002, 111(2):140-146.
82. Harlow E.G., et al. Critical period plasticity is disrupted in the barrel cortex of FMR1 knockout mice. Neuron 2010, 65(3):385-398.
83. Nithianantharajah J., Hannan A.J. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 2006, 7(9):697-709.
84. Restivo L., et al. Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome. Proc Natl Acad Sci U S A 2005, 102(32):11557-11562.
85. Bindu B., et al. Short-term exposure to an enriched environment enhances dendritic branching but not brain-derived neurotrophic factor expression in the hippocampus of rats with ventral subicular lesions. Neuroscience 2007, 144(2):412-423.
86. Kuzumaki N., et al. Hippocampal epigenetic modification at the brain-derived neurotrophic factor gene induced by an enriched environment. Hippocampus 2011, 21(2):127-132.
87. Castren M.L., Castren E. BDNF in fragile X syndrome. Neuropharmacology 2014, 76(Pt C):729-736.
88. Kazlauckas V., et al. Enriched environment effects on behavior, memory and BDNF in low and high exploratory mice. Physiol Behav 2011, 102(5):475-480.
89. Erickson C.A., et al. Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology (Berl) 2013, 228(1):75-84.
90. Hashimoto R., et al. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology 2002, 43(7):1173-1179.
91. Liu Z.H., Chuang D.M., Smith C.B. Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int J Neuropsychopharmacol 2011, 14(5):618-630.
92. Shim S.S., Hammonds M.D., Mervis R.F. Four weeks lithium treatment alters neuronal dendrites in the rat hippocampus. Int J Neuropsychopharmacol 2013, 16(6):1373-1382.
93. Vigers A.J., et al. Sustained expression of brain-derived neurotrophic factor is required for maintenance of dendritic spines and normal behavior. Neuroscience 2012, 212:1-18.
94. Gorski J.A., et al. Brain-derived neurotrophic factor is required for the maintenance of cortical dendrites. J Neurosci 2003, 23(17):6856-6865.
95. Kline D.D., et al. Exogenous brain-derived neurotrophic factor rescues synaptic dysfunction in Mecp2-null mice. J Neurosci 2010, 30(15):5303-5310.
96. Zhang X., et al. Intrinsic membrane properties of locus coeruleus neurons in Mecp2-null mice. Am J Physiol Cell Physiol 2010, 298(3):C635-C646.
97. Na E.S., et al. A mouse model for MeCP2 duplication syndrome: MeCP2 overexpression impairs learning and memory and synaptic transmission. J Neurosci 2012, 32(9):3109-3117.
98. Shepherd G.M., Katz D.M. Synaptic microcircuit dysfunction in genetic models of neurodevelopmental disorders: focus on Mecp2 and Met. Curr Opin Neurobiol 2011, 21(6):827-833.
99. Zhou Z., et al. Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron 2006, 52(2):255-269.
100. Chapleau C.A., et al. Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations. Neurobiol Dis 2009, 35(2):219-233.
101. Jiang M., et al. Dendritic arborization and spine dynamics are abnormal in the mouse model of MECP2 duplication syndrome. J Neurosci 2013, 33(50):19518-19533.
102. Wang H., et al. Dysregulation of brain-derived neurotrophic factor expression and neurosecretory function in Mecp2 null mice. J Neurosci 2006, 26(42):10911-10915.
103. Goto Y., Grace A.A. Alterations in medial prefrontal cortical activity and plasticity in rats with disruption of cortical development. Biol Psychiatry 2006, 60(11):1259-1267.
104. Rubinstein M., et al. Dopamine D4 receptor-deficient mice display cortical hyperexcitability. J Neurosci 2001, 21(11):3756-3763.
105. Savanthrapadian S., et al. Enhanced hippocampal neuronal excitability and LTP persistence associated with reduced behavioral flexibility in the maternal immune activation model of schizophrenia. Hippocampus 2013, 23(12):1395-1409.
106. Weickert C.S., et al. Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Mol Psychiatry 2003, 8(6):592-610.
107. Weickert C.S., et al. Reductions in neurotrophin receptor mRNAs in the prefrontal cortex of patients with schizophrenia. Mol Psychiatry 2005, 10(7):637-650.
108. Hashimoto T., et al. Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia. J Neurosci 2005, 25(2):372-383.
109. + and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. J Psychiatry Neurosci 2011, 36(3):195-203.
110. Glantz L.A., Lewis D.A. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 2000, 57(1):65-73.
111. Hill J.J., et al. Analysis of pyramidal neuron morphology in an inducible knockout of brain-derived neurotrophic factor. Biol Psychiatry 2005, 57(8):932-934.
112. Kalus P., et al. The dendritic architecture of prefrontal pyramidal neurons in schizophrenic patients. Neuroreport 2000, 11(16):3621-3625.
113. Silva-Gomez A.B., et al. Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats. Brain Res 2003, 983(1-2):128-136.
114. Kolomeets N.S., et al. Ultrastructural alterations in hippocampal mossy fiber synapses in schizophrenia: a postmortem morphometric study. Synapse 2005, 57(1):47-55.
115. Bateup H.S., et al. Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function. J Neurosci 2011, 31(24):8862-8869.
116. Yoshii A., Constantine-Paton M. Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol 2010, 70(5):304-322.
117. Tavazoie S.F., et al. Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat Neurosci 2005, 8(12):1727-1734.
118. Han J.M., Sahin M. TSC1/TSC2 signaling in the CNS. FEBS Lett 2011, 585(7):973-980.
119. Lu B. BDNF and activity-dependent synaptic modulation. Learn Mem 2003, 10(2):86-98.
120. Bhattacharya A., et al. Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron 2012, 76(2):325-337.
121. Pan Y., Berman Y., Carr K.D. Effects of the group I metabotropic glutamate receptor agonist, DHPG, and injection stress on striatal cell signaling in food-restricted and ad libitum fed rats. BMC Neurosci 2004, 5:50.
122. Muddashetty R.S., et al. Dysregulated metabotropic glutamate receptor-dependent translation of AMPA receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of fragile X syndrome. J Neurosci 2007, 27(20):5338-5348.
123. Enriquez-Barreto L., et al. Learning improvement after PI3K activation correlates with de novo formation of functional small spines. Front Mol Neurosci 2014, 6:54.
124. Jaworski J., et al. Control of dendritic arborization by the phosphoinositide-3'-kinase-Akt-mammalian target of rapamycin pathway. J Neurosci 2005, 25(49):11300-11312.
125. Wayman G.A., et al. Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron 2006, 50(6):897-909.
126. Pi H.J., et al. CaMKII control of spine size and synaptic strength: role of phosphorylation states and nonenzymatic action. Proc Natl Acad Sci U S A 2010, 107(32):14437-14442.
127. Ha S., Redmond L. ERK mediates activity dependent neuronal complexity via sustained activity and CREB-mediated signaling. Dev Neurobiol 2008, 68(14):1565-1579.
128. Yasuda S., et al. Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2beta and p38 MAP kinases. Neuron 2007, 56(3):456-471.
129. Ji R.R., et al. P38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 2002, 36(1):57-68.
130. Shieh P.B., Ghosh A. Molecular mechanisms underlying activity-dependent regulation of BDNF expression. J Neurobiol 1999, 41(1):127-134.
131. Viwatpinyo K., Chongthammakun S. Activation of group I metabotropic glutamate receptors leads to brain-derived neurotrophic factor expression in rat C6 cells. Neurosci Lett 2009, 467(2):127-130.
132. Obrietan K., Gao X.B., Van Den Pol A.N. Excitatory actions of GABA increase BDNF expression via a MAPK-CREB-dependent mechanism - a positive feedback circuit in developing neurons. J Neurophysiol 2002, 88(2):1005-1015.
133. Chen M.J., et al. Norepinephrine induces BDNF and activates the PI-3K and MAPK cascades in embryonic hippocampal neurons. Cell Signal 2007, 19(1):114-128.
134. Obata K., et al. Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury. J Neurosci 2003, 23(10):4117-4126.
135. Hisatsune C., et al. Inositol 1,4,5-trisphosphate receptor type 1 in granule cells, not in Purkinje cells, regulates the dendritic morphology of Purkinje cells through brain-derived neurotrophic factor production. J Neurosci 2006, 26(42):10916-10924.
136. Canossa M., et al. Regulated secretion of neurotrophins by metabotropic glutamate group I (mGluRI) and Trk receptor activation is mediated via phospholipase C signalling pathways. EMBO J 2001, 20(7):1640-1650.
137. Bagayogo I.P., Dreyfus C.F. Regulated release of BDNF by cortical oligodendrocytes is mediated through metabotropic glutamate receptors and the PLC pathway. ASN Neuro 2009, 1(1):1-12.
138. Jean Y.Y., Lercher L.D., Dreyfus C.F. Glutamate elicits release of BDNF from basal forebrain astrocytes in a process dependent on metabotropic receptors and the PLC pathway. Neuron Glia Biol 2008, 4(1):35-42.
139. 2+ levels. Neuroreport 2005, 16(9):977-980.
140. Gross C., et al. Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome. J Neurosci 2010, 30(32):10624-10638.
141. Osterweil E.K., et al. Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome. J Neurosci 2010, 30(46):15616-15627.
142. Hou L., et al. Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron 2006, 51(4):441-454.
143. Gibson J.R., et al. Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome. J Neurophysiol 2008, 100(5):2615-2626.
144. Goncalves J.T., et al. Circuit level defects in the developing neocortex of Fragile X mice. Nat Neurosci 2013, 16(7):903-909.
145. Jacquemont S., et al. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med 2011, 3(64):64ra1.
146. National Institute of Mental Health; A multi-centre, randomized, double-blind, placebo controlled, two-period, crossover proof-of-concept study in male patients with Fragile X syndrome to assess the efficacy, safety and tolerability of multiple oral doses of AFQ056. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2014 Mar 08]. Available from: clinicaltrials.gov/ct2/show/NCT00718341 NLM Identifier: NCT00718341.
147. Nakayama A.Y., Harms M.B., Luo L. Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J Neurosci 2000, 20(14):5329-5338.
148. Lee A., et al. Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1. Development 2003, 130(22):5543-5552.