Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: Fundamental roles in neurodevelopmental disorders associated with mental retardation and autism

Journal of Neurodevelopmental Disorders

Volumn 1, Issue 3, 2009, Pages 185-196

  Chapleau, Christopher A ^a   Larimore, Jennifer L ^a   Theibert, Anne ^a   Pozzo Miller, Lucas ^a  

^a University of Alabama at Birmingham   (United States)

Author keywords

Autism; BDNF; Dendritic spine; Hippocampus; Mental retardation; Pyramidal neuron; Rett syndrome; Vesicle trafficking

Indexed keywords

EID: 78751500005     PISSN: 18661947     EISSN: 18661955     Source Type: Journal    
DOI: 10.1007/s11689-009-9027-6     Document Type: Article

References (157)

1. Ziv NE, Smith SJ. Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron. 1996;17:91-102.
2. Fischer M, Kaech S, Knutti D, Matus A. Rapid actin-based plasticity in dendritic spines. Neuron. 1998;20:847-54.
3. Dunaevsky A, Tashiro A, Majewska A, Mason C, Yuste R. Developmental regulation of spine motility in the mammalian central nervous system. Proc Natl Acad Sci USA. 1999;96:13438-43.
4. Grutzendler J, Kasthuri N, Gan WB. Long-term dendritic spine stability in the adult cortex. Nature. 2002;420:812-6.
5. Trachtenberg JT, Chen BE, Knott GW, Feng G, Sanes JR, Welker E, et al. Long-term in vivo imaging of experience dependent synaptic plasticity in adult cortex. Nature. 2002;420:788-94.
6. Mizrahi A, Crowley JC, Shtoyerman E, Katz LC. Highresolution in vivo imaging of hippocampal dendrites and spines. J Neurosci. 2004;24:3147-51.
7. Yuste R, Bonhoeffer T. Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci. 2001;24:1071-89.
8. Nimchinsky EA, Sabatini BL, Svoboda K. Structure and function of dendritic spines. Annu Rev Physiol. 2002;64:313-53.
9. Ethell IM, Pasquale EB. Molecular mechanisms of dendritic spine development and remodeling. Prog Neurobiol. 2005;75:161-205.
10. Segal M. Dendritic spines and long-term plasticity. Nat Rev Neurosci. 2005;6:277-84.
11. Peters A, Kaiserman-Abramof I. The small pyramidal neuron of the rat cerebral cortex. The perikarion, dendrites and spines. J Anat. 1970;127:321-56.
12. Korkotian E, Holcman D, Segal M. Dynamic regulation of spinedendrite coupling in cultured hippocampal neurons. Eur J Neurosci. 2004;20:2649-63.
13. Noguchi J, Matsuzaki M, Ellis-Davies GC, Kasai H. Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in dendrites. Neuron. 2005;46:609-22.
14. Matsuzaki M, Ellis-Davies GC, Nemoto T, Miyashita Y, Iino M, Kasai H. Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat Neurosci. 2001;4:1086-92.
15. Knott GW, Holtmaat A, Wilbrecht L, Welker E, Svoboda K. Spine growth precedes synapse formation in the adult neocortex in vivo. Nat Neurosci. 2006;9:1117-24.
16. Parnass Z, Tashiro A, Yuste R. Analysis of spine morphological plasticity in developing hippocampal pyramidal neurons. Hippocampus. 2000;10:561-8.
17. Holtmaat AJ, Trachtenberg JT, Wilbrecht L, Shepherd GM, Zhang X, Knott GW, et al. Transient and persistent dendritic spines in the neocortex in vivo. Neuron. 2005;45:279-91.
18. Chapleau CA, Pozzo-Miller L. Activity-dependent structural plasticity of dendritic spines. In: Byrne J, editor. Concise learning and memory: the editor's selection. Oxford: Elsevier; 2007. p. 281-305.
19. Matsuo N, Reijmers L, Mayford M. Spine-type-specific recruitment of newly synthesized AMPA receptors with learning. Science. 2008;319:1104-7.
20. McKinney RA, Capogna M, Durr R, Gahwiler BH, Thompson SM. Miniature synaptic events maintain dendritic spines via AMPA receptor activation. Nat Neurosci. 1999;2:44-9.
21. Lewin GR, Barde YA. Physiology of the neurotrophins. Annu Rev Neurosci. 1996;19:289-317.
22. Black IB. Trophic regulation of synaptic plasticity. J Neurobiol. 1999;41:108-18.
23. Poo MM. Neurotrophins as synaptic modulators. Nat Rev Neurosci. 2001;2:24-32.
24. Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller LD. From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem. 2002;9:224-37.
25. Vicario-Abejon C, Owens D, McKay R, Segal M. Role of neurotrophins in central synapse formation and stabilization. Nat Rev Neurosci. 2002;3:965-74.
26. Amaral MD, Chapleau CA, Pozzo-Miller L. Transient receptor potential channels as novel effectors of brain-derived neurotrophic factor signaling: potential implications for Rett syndrome. Pharmacol Ther. 2007;113:394-409.
27. Murer MG, Yan Q, Raisman-Vozari R. Brain-derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease. Prog Neurobiol. 2001;63:71-124.
28. Tyler W, Pozzo-Miller L. BDNF enhances quantal neurotransmitter release and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses. J Neurosci. 2001;21:4249-58.
29. Barbacid M. Nerve growth factor: a tale of two receptors. Oncogene. 1993;8:2033-42.
30. Reichardt LF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 2006;361:1545-64.
31. Segal RA, Greenberg ME. Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci. 1996;19:463-89.
32. Alonso M, Medina JH, Pozzo-Miller L. ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons. LearnMem. 2004;11:172-8.
33. Amaral MD, Pozzo-Miller L. BDNF induces calcium elevations associated with IBDNF, a nonselective cationic current mediated by TRPC channels. J Neurophysiol. 2007;98:2476-82.
34. Ji Y, Pang PT, Feng L, Lu B. Cyclic AMP controls BDNFinduced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons. Nat Neurosci. 2005;8:164-72.
35. Amaral MD, Pozzo-Miller L. TRPC3 channels are necessary for brain-derived neurotrophic factor to activate a nonselective cationic current and to induce dendritic spine formation. J Neurosci. 2007;27:5179-89.
36. Hartmann M, Brigadski T, Erdmann KS, Holtmann B, Sendtner M, Narz F, et al. Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor. J Cell Sci. 2004;117:5803-14.
37. Zagrebelsky M, Holz A, Dechant G, Barde YA, Bonhoeffer T, Korte M. The p75 neurotrophin receptor negatively modulates dendrite complexity and spine density in hippocampal neurons. J Neurosci. 2005;25:9989-99.
38. Tyler W, Pozzo-Miller L. Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones. J Physiol. 2003;553:497-509.
39. Tyler WJ, Perrett SP, Pozzo-Miller LD. The role of neurotrophins in neurotransmitter release. Neuroscientist. 2002;8:524-31.
40. Balkowiec A, Katz DM. Cellular mechanisms regulating activitydependent release of native brain-derived neurotrophic factor from hippocampal neurons. J Neurosci. 2002;22:10399-407.
41. Gartner A, Staiger V. Neurotrophin secretion from hippocampal neurons evoked by long-term-potentiation-inducing electrical stimulation patterns. Proc Natl Acad Sci USA. 2002;99:6386-91.
42. Aicardi G, Argilli E, Cappello S, Santi S, Riccio M, Thoenen H, et al. Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor. Proc Natl Acad Sci USA. 2004;101:15788-92.
43. Brigadski T, Hartmann M, Lessmann V. Differential vesicular targeting and time course of synaptic secretion of the mammalian neurotrophins. J Neurosci. 2005;25:7601-14.
44. Matsumoto T, Rauskolb S, Polack M, Klose J, Kolbeck R, Korte M, et al. Biosynthesis and processing of endogenous BDNF: CNS neurons store and secrete BDNF, not pro-BDNF. Nat Neurosci. 2008;11:131-3.
45. Nagappan G, Zaitsev E, Senatorov VV Jr, Yang J, Hempstead BL, Lu B. Control of extracellular cleavage of ProBDNF by high frequency neuronal activity. Proc Natl Acad Sci USA. 2009;106:1267-72.
46. Yang J, Siao CJ, Nagappan G, Marinic T, Jing D, McGrath K, et al. Neuronal release of proBDNF. Nat Neurosci. 2009;12:113-5.
47. Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nat Rev Neurosci. 2005;6:603-14.
48. Bourne J, Harris KM. Do thin spines learn to be mushroom spines that remember? Curr Opin Neurobiol. 2007;17:381-6.
49. Chapleau CA, Carlo ME, Larimore JL, Pozzo-Miller L. The actions of BDNF on dendritic spine density and morphology in organotypic slice cultures depend on the presence of serum in culture media. J Neurosci Meth. 2008;169:182-90.
50. Tanaka J, Horiike Y, Matsuzaki M, Miyazaki T, Ellis-Davies GC, Kasai H. Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science. 2008;319:1683-7.
51. Pozzo-Miller L. BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons. Brain Res. 2006;1104:45-54.
52. Tyler WJ, Zhang XL, Hartman K, Winterer J, Muller W, Stanton PK, et al. BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses. J Physiol. 2006;574:787-803.
53. Bramham CR, Messaoudi E. BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol. 2005;76:99-125.
54. Kaufmann WE, Moser HW. Dendritic anomalies in disorders associated with mental retardation. Cereb Cortex. 2000;10:981-91.
55. Fiala JC, Spacek J, Harris KM. Dendritic spine pathology: cause or consequence of neurological disorders? Brain Res Rev. 2002;39:29-54.
56. Huttenlocher PR. Dendritic development and mental defect. Neurology. 1970;20:381.
57. Marin-Padilla M. Structural abnormalities of the cerebral cortex in human chromosomal aberrations: a Golgi study. Brain Res. 1972;44:625-9.
58. Huttenlocher PR. Dendritic development in neocortex of children with mental defect and infantile spasms. Neurology. 1974;24:203-10.
59. Purpura DP. Dendritic spine "dysgenesis" and mental retardation. Science. 1974;186:1126-8.
60. Purpura DP. Normal and aberrant neuronal development in the cerebral cortex of human fetus and young infant. UCLA Forum Med Sci 1975; 141-169.
61. Marin-Padilla M. Pyramidal cell abnormalities in the motor cortex of a child with Down's syndrome. A Golgi study. J Comp Neurol. 1976;167:63-81.
62. Newey SE, Velamoor V, Govek EE, Van Aelst L. Rho GTPases, dendritic structure, and mental retardation. J Neurobiol. 2005;64:58-74.
63. Schanen NC. Epigenetics of autism spectrum disorders. Hum Mol Genet 2006; 15 Spec No 2:R138-50.
64. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23:185-8.
65. Percy AK, Lane JB. Rett syndrome: clinical and molecular update. Curr Opin Pediatr. 2004;16:670-7.
66. Nan X, Campoy FJ, Bird A. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell. 1997;88:471-81.
67. Nan X, Cross S, Bird A. Gene silencing by methyl-CpG-binding proteins. Novartis Found Symp. 1998;214:6-16. discussion 16-21, 46-50.
68. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet. 1998;19:187-91.
69. Klose RJ, Sarraf SA, Schmiedeberg L, McDermott SM, Stancheva I, Bird AP. DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG. Mol Cell. 2005;19:667-78.
70. Bauman ML, Kemper TL, Arin DM. Pervasive neuroanatomic abnormalities of the brain in three cases of Rett's syndrome. Neurology. 1995;45:1581-6.
71. Bauman ML, Kemper TL, Arin DM. Microscopic observations of the brain in Rett syndrome. Neuropediatrics. 1995;26:105-8.
72. Armstrong D, Dunn JK, Antalffy B, Trivedi R. Selective dendritic alterations in the cortex of Rett syndrome. J Neuropathol Exp Neurol. 1995;54:195-201.
73. Kaufmann WE, Naidu S, Budden S. Abnormal expression of microtubule-associated protein 2 (MAP-2) in neocortex in Rett syndrome. Neuropediatrics. 1995;26:109-13.
74. Kaufmann WE, Taylor CV, Hohmann CF, Sanwal IB, Naidu S. Abnormalities in neuronal maturation in Rett syndrome neocortex: preliminary molecular correlates. Eur Child Adolesc Psychiatry. 1997;6(Suppl 1):75-7.
75. Kaufmann WE, MacDonald SM, Altamura CR. Dendritic cytoskeletal protein expression in mental retardation: an immunohistochemical study of the neocortex in Rett syndrome. Cereb Cortex. 2000;10:992-1004.
76. Belichenko PV, Oldfors A, Hagberg B, Dahlstrom A. Rett syndrome: 3-D confocal microscopy of cortical pyramidal dendrites and afferents. Neuroreport. 1994;5:1509-13.
77. Chapleau CA, Calfa GD, Lane MC, Albertson AJ, Larimore JL, Kudo S, Armstrong DL, Percy AK, Pozzo-Miller L. Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations. Neurobiol Dis. 2009;35:219-33.
78. Naidu S. Rett syndrome: a disorder affecting early brain growth. Ann Neurol. 1997;42:3-10.
79. Kaufmann WE, Johnston MV, Blue ME. MeCP2 expression and function during brain development: implications for Rett syndrome's pathogenesis and clinical evolution. Brain Dev. 2005;27(Suppl 1):S77-87.
80. Chahrour M, Zoghbi HY. The story of Rett syndrome: from clinic to neurobiology. Neuron. 2007;56:422-37.
81. Chen RZ, Akbarian S, Tudor M, Jaenisch R. Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rettlike phenotype in mice. Nat Genet. 2001;27:327-31.
82. Guy J, Hendrich B, Holmes M, Martin JE, Bird A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet. 2001;27:322-6.
83. Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, et al. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron. 2002;35:243-54.
84. Armstrong DD. Neuropathology of Rett syndrome. J Child Neurol. 2005;20:747-53.
85. Dani VS, Chang Q, Maffei A, Turrigiano GG, Jaenisch R, Nelson SB. Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome. Proc Natl Acad Sci USA. 2005;102: 12560-5.
86. Nelson ED, Kavalali ET, Monteggia LM. MeCP2-dependent transcriptional repression regulates excitatory neurotransmission. Curr Biol. 2006;16:710-6.
87. Asaka Y, Jugloff DG, Zhang L, Eubanks JH, Fitzsimonds RM. Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiol Dis. 2006;21:217-27.
88. Moretti P, Levenson JM, Battaglia F, Atkinson R, Teague R, Antalffy B, et al. Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. J Neurosci. 2006;26:319-27.
89. Collins AL, Levenson JM, Vilaythong AP, Richman R, Armstrong DL, Noebels JL, et al. Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet. 2004;13:2679-89.
90. Chao HT, Zoghbi HY, Rosenmund C. MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron. 2007;56:58-65.
91. Zhou Z, Hong EJ, Cohen S, Zhao WN, Ho HY, Schmidt L, et al. Brain-specific phosphorylation of MeCP2 regulates activitydependent Bdnf transcription, dendritic growth, and spine maturation. Neuron. 2006;52:255-69.
92. Belichenko NP, Belichenko PV, Mobley WC. Evidence for both neuronal cell autonomous and nonautonomous effects of methyl-CpG-binding protein 2 in the cerebral cortex of female mice with Mecp2 mutation. Neurobiol Dis. 2009;34:71-7.
93. Belichenko PV, Wright EE, Belichenko NP, Masliah E, Li HH, Mobley WC, et al. Widespread changes in dendritic and axonal morphology in Mecp2-mutant mouse models of Rett syndrome: evidence for disruption of neuronal networks. J Comp Neurol. 2009;514:240-58.
94. Kishi N, Macklis JD. MECP2 is progressively expressed in postmigratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol Cell Neurosci. 2004;27:306-21.
95. Fukuda T, Itoh M, Ichikawa T, Washiyama K, Goto Y. Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. J Neuropathol Exp Neurol. 2005;64:537-44.
96. Smrt RD, Eaves-Egenes J, Barkho BZ, Santistevan NJ, Zhao C, Aimone JB, et al. Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. Neurobiol Dis. 2007;27:77-89.
97. Cusack SM, Rohn TT, Medeck RJ, Irwin KM, Brown RJ, Mercer LM, et al. Suppression of MeCP2beta expression inhibits neurite extension in PC12 cells. Exp Cell Res. 2004;299:442-53.
98. Jugloff DG, Jung BP, Purushotham D, Logan R, Eubanks JH. Increased dendritic complexity and axonal length in cultured mouse cortical neurons overexpressing methyl-CpG-binding protein MeCP2. Neurobiol Dis. 2005;19:18-27.
99. Ballas N, Lioy DT, Grunseich C, Mandel G. Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat Neurosci. 2009;12:311-7.
100. Maezawa I, Swanberg S, Harvey D, LaSalle JM, Jin LW. Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci. 2009;29:5051-61.
101. Chang Q, Khare G, Dani V, Nelson S, Jaenisch R. The disease progression of Mecp2 mutant mice Is affected by the level of BDNF expression. Neuron. 2006;49:341-8.
102. Larimore JL, Chapleau CA, Kudo S, Theibert A, Percy AK, Pozzo-Miller L. Bdnf overexpression in hippocampal neurons prevents dendritic atrophy caused by Rett-associated MECP2 mutations. Neurobiol Dis. 2009;34:199-211.
103. Ogier M, Wang H, Hong E, Wang Q, Greenberg ME, Katz DM. Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J Neurosci. 2007;27:10912-7.
104. Lauterborn JC, Lynch G, Vanderklish P, Arai A, Gall CM. Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J Neurosci. 2000;20:8-21.
105. Lynch G, Gall CM. Ampakines and the threefold path to cognitive enhancement. Trends Neurosci. 2006;29:554-62.
106. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, et al. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci USA. 2009;106:2029-34.
107. Guy J, Gan J, Selfridge J, Cobb S, Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science. 2007;315:1143-7.
108. Ehninger D, Li W, Fox K, Stryker MP, Silva AJ. Reversing neurodevelopmental disorders in adults. Neuron. 2008;60:950-60.
109. Bienvenu T, Chelly J. Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized. Nat Rev Genet. 2006;7:415-26.
110. Ballestar E, Ropero S, Alaminos M, Armstrong J, Setien F, Agrelo R, et al. The impact of MECP2 mutations in the expression patterns of Rett syndrome patients. Hum Genet. 2005;116:91-104.
111. Nuber UA, Kriaucionis S, Roloff TC, Guy J, Selfridge J, Steinhoff C, et al. Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett syndrome. Hum Mol Genet. 2005;14:2247-56.
112. Delgado IJ, Kim DS, Thatcher KN, Lasalle JM, Van den Veyver IB. Expression profiling of clonal lymphocyte cell cultures from Rett syndrome patients. BMC Med Genet. 2006;7:61.
113. Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC, et al. Derepression of BDNF transcription involves calciumdependent phosphorylation of MeCP2. Science. 2003;302:885-9.
114. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, et al. DNA methylation-related chromatin remodeling in activity dependent BDNF gene regulation. Science. 2003;302:890-3.
115. Abuhatzira L, Makedonski K, Kaufman Y, Razin A, Shemer R. MeCP2 deficiency in the brain decreases BDNF levels by REST/ CoREST-mediated repression and increases TRKB production. Epigenetics. 2007;4:214-22.
116. Deng V, Matagne V, Banine F, Frerking M, Ohliger P, Budden S, et al. FXYD1 is an MeCP2 target gene overexpressed in the brains of Rett syndrome patients and Mecp2-null mice. Hum Mol Genet. 2007;16:640-50.
117. Lappalainen R, Lindholm D, Riikonen R. Low levels of nerve growth factor in cerebrospinal fluid of children with Rett syndrome. J Child Neurol. 1996;11:296-300.
118. Vanhala R, Korhonen L, Mikelsaar M, Lindholm D, Riikonen R. Neurotrophic factors in cerebrospinal fluid and serum of patients with Rett syndrome. J Child Neurol. 1998;13:429-33.
119. Riikonen R, Vanhala R. Levels of cerebrospinal fluid nervegrowth factor differ in infantile autism and Rett syndrome. Dev Med Child Neurol. 1999;41:148-52.
120. Riikonen R. Neurotrophic factors in the pathogenesis of Rett syndrome. J Child Neurol. 2003;18:693-7.
121. Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME. Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron. 1998;20:709-26.
122. Klein ME, Lioy DT, Ma L, Impey S, Mandel G, Goodman RH. Homeostatic regulation of MeCP2 expression by a CREBinduced microRNA. Nat Neurosci. 2007;10:1513-4.
123. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science. 2008;320:1224-9.
124. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112:257-69.
125. Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, et al. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci. 2004;24:4401-11.
126. Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, et al. Genetic variant BDNF (Val66Met) polymorphism alters anxietyrelated behavior. Science. 2006;314:140-3.
127. Nectoux J, Bahi-Buisson N, Guellec I, Coste J, De Roux N, Rosas H, et al. The p.Val66Met polymorphism in the BDNF gene protects against early seizures in Rett syndrome. Neurology. 2008;70:2145-51.
128. Zeev BB, Bebbington A, Ho G, Leonard H, de Klerk N, Gak E, Vecksler M, Christodoulou J. The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome. Neurology. 2009;72:1242-7.
129. Parton RG, Schrotz P, Bucci C, Gruenberg J. Plasticity of early endosomes. J Cell Sci. 1992;103:335-48.
130. Stoorvogel W, Oorschot V, Geuze HJ. A novel class of clathrincoated vesicles budding from endosomes. J Cell Biol. 1996;132:21-33.
131. Bonifacino JS, Glick BS. The mechanisms of vesicle budding and fusion. Cell. 2004;116:153-66.
132. Racz B, Blanpied TA, Ehlers MD, Weinberg RJ. Lateral organization of endocytic machinery in dendritic spines. Nat Neurosci. 2004;7:917-8.
133. Park M, Salgado JM, Ostroff L, Helton TD, Robinson CG, Harris KM, et al. Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes. Neuron. 2006;52:817-30.
134. Roohi J, Tegay DH, Pomeroy JC, Burkett S, Stone G, Stanyon R, et al. A de novo apparently balanced translocation [46, XY, t (2;9)(p13;p24)] interrupting RAB11FIP5 identifies a potential candidate gene for autism spectrum disorder. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:411-7.
135. Edwards RH. Neurotransmitter release: variations on a theme. Curr Biol. 1998;8:R883-5.
136. Horton AC, Ehlers MD. Dual modes of endoplasmic reticulumto-Golgi transport in dendrites revealed by live-cell imaging. J Neurosci. 2003;23:6188-99.
137. Horton AC, Ehlers MD. Secretory trafficking in neuronal dendrites. Nat Cell Biol. 2004;6:585-91.
138. Horton AC, Racz B, Monson EE, Lin AL, Weinberg RJ, Ehlers MD. Polarized secretory trafficking directs cargo for asymmetric dendrite growth and morphogenesis. Neuron. 2005;48:757-71.
139. Urbe S, Page LJ, Tooze SA. Homotypic fusion of immature secretory granules during maturation in a cell-free assay. J Cell Biol. 1998;143:1831-44.
140. Tooze SA. Biogenesis of secretory granules Implications arising from the immature secretory granule in the regulated pathway of secretion. FEBS Lett. 1991;285:220-4.
141. Austin C, Hinners I, Tooze SA. Direct and GTP-dependent interaction of ADP-ribosylation factor 1 with clathrin adaptor protein AP-1 on immature secretory granules. J Biol Chem. 2000;275:21862-9.
142. Dittie A, Hajibagheri N, Tooze S. The AP-1 adaptor complex binds to immature secretory granules from PC12 cells, and is regulated by ADP-ribosylation factor. J Cell Biol. 1996;132:523-36.
143. Wang H, Chan SA, Ogier M, Hellard D, Wang Q, Smith C, et al. Dysregulation of brain-derived neurotrophic factor expression and neurosecretory function in Mecp2 null mice. J Neurosci. 2006;26:10911-5.
144. Campbell DB, Sutcliffe JS, Ebert PJ, Militerni R, Bravaccio C, Trillo S, et al. A genetic variant that disrupts MET transcription is associated with autism. Proc Natl Acad Sci USA. 2006;103:16834-9.
145. Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya KJ, Sekine Y, et al. Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism. Prog Neuro-Psychopharmacol Biol Psych. 2006;30:1529-31.
146. Katoh-Semba R, Tsuzuki M, Miyazaki N, Matsuda M, Nakagawa C, Ichisaka S, et al. A phase advance of the light-dark cycle stimulates production of BDNF, but not of other neurotrophins, in the adult rat cerebral cortex: association with the activation of CREB. J Neurochem. 2008;106: 2131-42.
147. Kwon C-H, Luikart BW, Powell CM, Zhou J, Matheny SA, Zhang W, et al. Pten regulates neuronal arborization and social interaction in mice. Neuron. 2006;50:377-88.
148. Meikle L, Talos DM, Onda H, Pollizzi K, Rotenberg A, Sahin M, et al. A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci. 2007;27:5546-58.
149. Wassink TH, Piven J, Vieland VJ, Jenkins L, Frantz R, Bartlett CW, et al. Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene. Am J Med Gen Part B: Neuropsych Gen. 2005;136B:36-44.
150. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, et al. Strong association of de novo copy number mutations with autism. Science. 2007;316:445-9.
151. Sadakata T, Washida M, Iwayama Y, Shoji S, Sato Y, Ohkura T, et al. Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients. J Clin Invest. 2007;117:931-43.
152. Sadakata T, Mizoguchi A, Sato Y, Katoh-Semba R, Fukuda M, Mikoshiba K, et al. The secretory granule-associated protein CAPS2 regulates neurotrophin release and cell survival. J Neurosci. 2004;24:43-52.
153. Sadakata T, Kakegawa W, Mizoguchi A, Washida M, Katoh-Semba R, Shutoh F, et al. Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release. J Neurosci. 2007;27:2472-82.
154. Nelson KB, Grether JK, Croen LA, Dambrosia JM, Dickens BF, Jelliffe LL, et al. Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann Neurol. 2001;49:597-606.
155. Miyazaki K, Narita N, Sakuta R, Miyahara T, Naruse H, Okado N, et al. Serum neurotrophin concentrations in autism and mental retardation: a pilot study. Brain Dev. 2004;26:292-5.
156. Connolly AM, Chez M, Streif EM, Keeling RM, Golumbek PT, Kwon JM, et al. Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy. Biol Psychiatry. 2006;59:354-63.
157. Katoh-Semba R, Wakako R, Komori T, Shigemi H, Miyazaki N, Ito H, et al. Age-related changes in BDNF protein levels in human serum: differences between autism cases and normal controls. Int J Dev Neurosci. 2007;25:367-72.