Platelets as a surrogate disease model of neurodevelopmental disorders: Insights from Fragile X Syndrome

Platelets

Volumn 29, Issue 2, 2018, Pages 113-124

  Pellerin, David ^a,b   Lortie, Audrey ^a   Corbin, François ^a  

^a UNIVERSITY OF SHERBROOKE   (Canada)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

Autism spectrum disorder; biomarkers; ERK; Fragile X Syndrome; intellectual disability; platelets

Indexed keywords

BIOLOGICAL MARKER; CYCLIC AMP; GELATINASE B; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ALZHEIMER DISEASE; AUTISM; CLINICAL TRIAL (TOPIC); DEGENERATIVE DISEASE; DISEASE MODEL; ENZYME ACTIVITY; FRAGILE X SYNDROME; HUMAN; MENTAL DISEASE; NERVE CELL; PATHOPHYSIOLOGY; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; SIGNAL TRANSDUCTION; THROMBOCYTE; ANIMAL; BLOOD; METABOLISM; MOUSE; PATHOLOGY;

ANIMALS; BLOOD PLATELETS; FRAGILE X SYNDROME; HUMANS; MICE; NEURODEVELOPMENTAL DISORDERS;

EID: 85034828846     PISSN: 09537104     EISSN: 13691635     Source Type: Journal    
DOI: 10.1080/09537104.2017.1317733     Document Type: Review

References (164)

1. Gallagher A, Hallahan B., Fragile X-associated disorders: A clinical overview. J Neurol 2012;259(3):401–413.
2. Hessl D, Nguyen DV, Green C, Chavez A, Tassone F, Hagerman RJ, et al. A solution to limitations of cognitive testing in children with intellectual disabilities: The case of fragile X syndrome. J Neurodev Disord 2009;1(1):33–45.
3. Wang LW, Berry-Kravis E, Hagerman RJ., Fragile X: Leading the way for targeted treatments in autism. Neurotherapeutics 2010;7(3):264–274.
4. Subramanian M, Timmerman CK, Schwartz JL, Pham DL, Meffert MK., Characterizing autism spectrum disorders by key biochemical pathways. Front Neurosci 2015;9:313.
5. Schaefer GB, Mendelsohn NJ., Genetics evaluation for the etiologic diagnosis of autism spectrum disorders. Genet Med 2008;10(1):4–12.
6. Sztainberg Y, Zoghbi HY., Lessons learned from studying syndromic autism spectrum disorders. Nat Neurosci 2016;19(11):1408–1417.
7. Fung LK, Quintin EM, Haas BW, Reiss AL., Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome. Curr Opin Neurol 2012;25(2):112–124.
8. Berry-Kravis E., Mechanism-based treatments in neurodevelopmental disorders: Fragile X syndrome. Pediatr Neurol 2014;50(4):297–302.
9. Newschaffer CJ, Croen LA, Daniels J, Giarelli E, Grether JK, Levy SE, et al. The epidemiology of autism spectrum disorders. Annu Rev Publ Health 2007;28:235–258.
10. Huttenlocher PR, Dabholkar AS., Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 1997;387(2):167–178.
11. Ghosh A, Michalon A, Lindemann L, Fontoura P, Santarelli L., Drug discovery for autism spectrum disorder: Challenges and opportunities. Nat Rev Drug Discov 2013;12(10):777–790.
12. Boyle CA, Boulet S, Schieve LA, Cohen RA, Blumberg SJ, Yeargin-Allsopp M, et al. Trends in the prevalence of developmental disabilities in US children, 1997-2008. Pediatrics 2011;127(6):1034–1042.
13. Prevalence of autism spectrum disorder among children aged. 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill Summ 2014;63 (2)1–21.
14. Werling DM, Geschwind DH., Sex differences in autism spectrum disorders. Curr Opin Neurol 2013;26(2):146–153.
15. Kelleher RJ, 3rd, Bear MF. The autistic neuron: Troubled translation? Cell 2008;135(3):401–406.
16. Gilman SR, Iossifov I, Levy D, Ronemus M, Wigler M, Vitkup D., Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses. Neuron 2011;70(5):898–907.
17. El-Fishawy P, State MW., The genetics of autism: Key issues, recent findings, and clinical implications. Psychiatr Clin North Am 2010;33(1):83–105.
18. Iossifov I, O’Roak BJ, Sanders SJ, Ronemus M, Krumm N, Levy D, et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 2014;515(7526):216–221.
19. Auerbach BD, Osterweil EK, Bear MF., Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 2011;480(7375):63–68.
20. Washbourne P., Synapse assembly and neurodevelopmental disorders. Neuropsychopharmacology 2015;40(1):4–15.
21. Bourgeron T., A synaptic trek to autism. Curr Opin Neurobiol 2009;19(2):231–234.
22. Benvenuto A, Moavero R, Alessandrelli R, Manzi B, Curatolo P., Syndromic autism: Causes and pathogenetic pathways. World J Pediatr 2009;5(3):169–176.
23. Peprah E., Fragile X syndrome: The FMR1 CGG repeat distribution among world populations. Ann Hum Genet 2012;76(2):178–191.
24. Hagerman RJ. The Physical and Behavioral Phenotype. In: Rj H, Pj H, editors. Fragile X Syndrome: Diagnosis, Treatment, and Research. 3rd ed. Baltimore: The Johns Hopkins University Press; 2002. p. 3–109.
25. Harris SW, Hessl D, Goodlin-Jones B, Ferranti J, Bacalman S, Barbato I, et al. Autism profiles of males with fragile X syndrome. Am J Ment Retard 2008;113(6):427–438.
26. Rogers SJ, Wehner DE, Hagerman R., The behavioral phenotype in fragile X: Symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. J Dev Behav Pediatr 2001;22(6):409–417.
27. Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox. Cell 1991;67(6):1047–1058.
28. Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991;65(5):905–914.
29. Khandjian EW., Biology of the fragile X mental retardation protein, an RNA-binding protein. Biochem Cell Biol 1999;77(4):331–342.
30. McCoy M, Poliquin-Duchesneau D, Corbin F., Molecular dynamics of FMRP and other RNA-binding proteins in MEG-01 differentiation: The role of mRNP complexes in non-neuronal development. Biochem Cell Biol 2016;94(6):597–608.
31. Lauziere V, Lessard M, Meunier AJ, McCoy M, Bergeron LJ, Corbin F., Unusual subcellular confinement of the fragile X mental retardation protein (FMRP) in circulating human platelets: Complete polyribosome dissociation. Biochimie 2012;94(4):1069–1073.
32. Ashley CT, Jr., Wilkinson KD, Reines D, Warren ST., FMR1 protein: Conserved RNP family domains and selective RNA binding. Science 1993;262(5133):563–566.
33. Khandjian EW, Huot ME, Tremblay S, Davidovic L, Mazroui R, Bardoni B., Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles. Proc Natl Acad Sci USA 2004;101(36):13357–13362.
34. Corbin F, Bouillon M, Fortin A, Morin S, Rousseau F, Khandjian EW., The fragile X mental retardation protein is associated with poly(A)+ mRNA in actively translating polyribosomes. Hum Mol Genet 1997;6(9):1465–1472.
35. Bassell GJ, Warren ST., Fragile X syndrome: Loss of local mRNA regulation alters synaptic development and function. Neuron 2008;60(2):201–214.
36. Darnell JC, Van Driesche SJ, Zhang C, Hung KY, Mele A, Fraser CE, et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 2011;146(2):247–261.
37. Darnell JC, Klann E., The translation of translational control by FMRP: Therapeutic targets for FXS. Nat Neurosci 2013;16(11):1530–1536.
38. Dolen G, Carpenter RL, Ocain TD, Bear MF., Mechanism-based approaches to treating fragile X. Pharmacol Ther 2010;127(1):78–93.
39. Bear MF, Huber KM, Warren ST., The mGluR theory of fragile X mental retardation. Trends Neurosci 2004;27(7):370–377.
40. Costa-Mattioli M, Sossin WS, Klann E, Sonenberg N., Translational control of long-lasting synaptic plasticity and memory. Neuron 2009;61(1):10–26.
41. Osterweil EK, Krueger DD, Reinhold K, Bear MF., 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.
42. Huber KM, Gallagher SM, Warren ST, Bear MF., Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci USA 2002;99(11):7746–7750.
43. Waung MW, Pfeiffer BE, Nosyreva ED, Ronesi JA, Huber KM., Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate. Neuron 2008;59(1):84–97.
44. Fmr1. knockout mice: A model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium. Cell 1994;78 (1)23–33.
45. Mientjes EJ, Nieuwenhuizen I, Kirkpatrick L, Zu T, Hoogeveen-Westerveld M, Severijnen L, et al. The generation of a conditional Fmr1 knock out mouse model to study Fmrp function in vivo. Neurobiol Dis 2006;21(3):549–555.
46. Kelley DJ, Bhattacharyya A, Lahvis GP, Yin JC, Malter J, Davidson RJ., The cyclic AMP phenotype of fragile X and autism. Neurosci Biobehav Rev 2008;32(8):1533–1543.
47. Lozano R, Hare EB, Hagerman RJ., Modulation of the GABAergic pathway for the treatment of fragile X syndrome. Neuropsychiatr Dis Treat 2014;10:1769–1779.
48. Curia G, Papouin T, Seguela P, Avoli M., Downregulation of tonic GABAergic inhibition in a mouse model of fragile X syndrome. Cereb Cortex 2009;19(7):1515–1520.
49. Olmos-Serrano JL, Paluszkiewicz SM, Martin BS, Kaufmann WE, Corbin JG, Huntsman MM., Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome. J Neurosci 2010;30(29):9929–9938.
50. Bilousova TV, Dansie L, Ngo M, Aye J, Charles JR, Ethell DW, et al. Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet 2009;46(2):94–102.
51. Janusz A, Milek J, Perycz M, Pacini L, Bagni C, Kaczmarek L, et al. The Fragile X mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses. J Neurosci 2013;33(46):18234–18241.
52. Kelley DJ, Davidson RJ, Elliott JL, Lahvis GP, Yin JC, Bhattacharyya A., The cyclic AMP cascade is altered in the fragile X nervous system. Plos One 2007;2(9):e931.
53. Bhattacharya A, Kaphzan H, Alvarez-Dieppa AC, Murphy JP, Pierre P, Klann E., Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron 2012;76(2):325–337.
54. Hou L, Antion MD, Hu D, Spencer CM, Paylor R, Klann E., Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron 2006;51(4):441–454.
55. Michalon A, Sidorov M, Ballard TM, Ozmen L, Spooren W, Wettstein JG, et al. Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron 2012;74(1):49–56.
56. Price TJ, Rashid MH, Millecamps M, Sanoja R, Entrena JM, Cervero F., Decreased nociceptive sensitization in mice lacking the fragile X mental retardation protein: Role of mGluR1/5 and mTOR. J Neurosci 2007;27(51):13958–13967.
57. Wang X, Snape M, Klann E, Stone JG, Singh A, Petersen RB, et al. Activation of the extracellular signal-regulated kinase pathway contributes to the behavioral deficit of fragile x-syndrome. J Neurochem 2012;121(4):672–679.
58. Gross C, Nakamoto M, Yao X, Chan CB, Yim SY, Ye K, 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.
59. Sharma A, Hoeffer CA, Takayasu Y, Miyawaki T, McBride SM, Klann E, et al. Dysregulation of mTOR signaling in fragile X syndrome. J Neurosci 2010;30(2):694–702.
60. Bolduc FV, Bell K, Cox H, Broadie KS, Tully T., Excess protein synthesis in Drosophila fragile X mutants impairs long-term memory. Nat Neurosci 2008;11(10):1143–1145.
61. Greenough WT, Klintsova AY, Irwin SA, Galvez R, Bates KE, Weiler IJ., Synaptic regulation of protein synthesis and the fragile X protein. Proc Natl Acad Sci USA 2001;98(13):7101–7106.
62. Irwin SA, Patel B, Idupulapati M, Harris JB, Crisostomo RA, Larsen BP, 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.
63. Nosyreva ED, Huber KM., Metabotropic receptor-dependent long-term depression persists in the absence of protein synthesis in the mouse model of fragile X syndrome. J Neurophysiol 2006;95(5):3291–3295.
64. Bear MF, Dolen G, Osterweil E, Fragile NN. X, : Translation in action. Neuropsychopharmacology 2008;33(1):84–87.
65. Hoeffer CA, Sanchez E, Hagerman RJ, Mu Y, Nguyen DV, Wong H, et al. Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome. Genes Brain Behav 2012;11(3):332–341.
66. Kazdoba TM, Leach PT, Silverman JL, Crawley JN., Modeling fragile X syndrome in the Fmr1 knockout mouse. Intractable Rare Dis Res 2014;3(4):118–133.
67. Berry-Kravis E, Des Portes V, Hagerman R, Jacquemont S, Charles P, Visootsak J, et al. Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. Sci Transl Med 2016;8(321):321ra5.
68. Jacquemont S, Curie A, Des Portes V, Mg T, Berry-Kravis E, Rj H, 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.
69. Berry-Kravis E, Krause SE, Block SS, Guter S, Wuu J, Leurgans S, et al. Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: A controlled trial. J Child Adolesc Psychopharmacol 2006;16(5):525–540.
70. Leigh MJ, Nguyen DV, Mu Y, Winarni TI, Schneider A, Chechi T, et al. A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome. J Dev Behav Pediatr 2013;34(3):147–155.
71. Berry-Kravis EM, Hessl D, Rathmell B, Zarevics P, Cherubini M, Walton-Bowen K, et al. Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: A randomized, controlled, phase 2 trial. Sci Transl Med 2012;4(152):152ra127.
72. De Vrij FM, Levenga J, Van Der Linde HC, Koekkoek SK, De Zeeuw CI, Nelson DL, et al. Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol Dis 2008;31(1):127–132.
73. Gantois I, Pop AS, De Esch CE, Buijsen RA, Pooters T, Gomez-Mancilla B, et al. Chronic administration of AFQ056/Mavoglurant restores social behaviour in Fmr1 knockout mice. Behav Brain Res 2013;239:72–79.
74. Pop AS, Levenga J, de Esch CE, Buijsen RA, Nieuwenhuizen IM, Li T, et al. Rescue of dendritic spine phenotype in Fmr1 KO mice with the mGluR5 antagonist AFQ056/Mavoglurant. Psychopharmacology (Berl) 2014;231 (6)1227–1235.
75. Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP., Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 2005;49(7):1053–1066.
76. Levenga J, Hayashi S, de Vrij FM, Koekkoek SK, van der Linde HC, Nieuwenhuizen I, et al. AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome. Neurobiol Dis 2011;42 (3)311–317.
77. Berry-Kravis E, Hessl D, Abbeduto L, Reiss AL, Beckel-Mitchener A, Urv TK., Outcome measures for clinical trials in fragile X syndrome. J Dev Behav Pediatr 2013;34(7):508–522.
78. Spencer CM, Alekseyenko O, Hamilton SM, Thomas AM, Serysheva E, Yuva-Paylor LA, et al. Modifying behavioral phenotypes in Fmr1KO mice: Genetic background differences reveal autistic-like responses. Autism Res 2011;4(1):40–56.
79. Gross C, Bassell GJ., Excess protein synthesis in FXS patient lymphoblastoid cells can be rescued with a p110beta-selective inhibitor. Mol Med 2012;18:336–345.
80. Berry-Kravis E, Hicar M, Ciurlionis R., Reduced cyclic AMP production in fragile X syndrome: Cytogenetic and molecular correlations. Pediatr Res 1995;38(5):638–643.
81. Weng N, Weiler IJ, Sumis A, Berry-Kravis E, Greenough WT., Early-phase ERK activation as a biomarker for metabolic status in fragile X syndrome. Am J Med Genet B Neuropsychiatr Genet 2008;147b(7):1253–1257.
82. Pellerin D, Caku A, Fradet M, Bouvier P, Dube J, Corbin F., Lovastatin corrects ERK pathway hyperactivation in fragile X syndrome: Potential of platelet’s signaling cascades as new outcome measures in clinical trials. Biomarkers 2016;21(6):497–508.
83. Lessard M, Chouiali A, Drouin R, Sebire G, Corbin F., Quantitative measurement of FMRP in blood platelets as a new screening test for fragile X syndrome. Clin Genet 2012;82(5):472–477.
84. Berry-Kravis E, Huttenlocher PR., Cyclic AMP metabolism in fragile X syndrome. Ann Neurol 1992;31(1):22–26.
85. Berry-Kravis E, Sklena P., Demonstration of abnormal cyclic AMP production in platelets from patients with fragile X syndrome. Am J Med Genet 1993;45(1):81–87.
86. Kumari D, Bhattacharya A, Nadel J, Moulton K, Zeak NM, Glicksman A, et al. Identification of fragile X syndrome specific molecular markers in human fibroblasts: A useful model to test the efficacy of therapeutic drugs. Hum Mutat 2014;35(12):1485–1494.
87. Berk M., Platelet Glutamate Receptors as a Window into Psychiatric Disorders. In: Gill S, Pulido O, editors. Glutamate Receptors in Peripheral Tissue: Excitatory Transmission Outside the CNS. 1. New York: Springer; 2005. p. 233–241.
88. Asor E, Ben-Shachar D., Platelets: A possible glance into brain biological processes in schizophrenia. World J Psychiatry 2012;2(6):124–133.
89. Camacho A, Dimsdale JE., Platelets and psychiatry: Lessons learned from old and new studies. Psychosom Med 2000;62(3):326–336.
90. Ehrlich D, Humpel C., Platelets in psychiatric disorders. World J Psychiatry 2012;2(6):91–94.
91. Talib LL, Joaquim HP, Forlenza OV., Platelet biomarkers in Alzheimer’s disease. World J Psychiatry 2012;2(6):95–101.
92. Baier PC, Koch JM, Seeck-Hirschner M, Ohlmeyer K, Wilms S, Aldenhoff JB, et al. A flow-cytometric method to investigate glutamate-receptor-sensitivity in whole blood platelets - results from healthy controls and patients with schizophrenia. J Psychiatr Res 2009;43(6):585–591.
93. Berk M, Plein H, Belsham B., The specificity of platelet glutamate receptor supersensitivity in psychotic disorders. Life Sci 2000;66(25):2427–2432.
94. Berk M, Plein H, Csizmadia T., Supersensitive platelet glutamate receptors as a possible peripheral marker in schizophrenia. Int Clin Psychopharmacol 1999;14(2):119–122.
95. Mangano RM, Schwarcz R., The human platelet as a model for the glutamatergic neuron: Platelet uptake of L-glutamate. J Neurochem 1981;36(3):1067–1076.
96. Boyanova D, Nilla S, Birschmann I, Dandekar T, Dittrich M., PlateletWeb: A systems biologic analysis of signaling networks in human platelets. Blood 2012;119(3):e22–e34.
97. Aslan JE, Tormoen GW, Loren CP, Pang J, McCarty OJ., S6K1 and mTOR regulate Rac1-driven platelet activation and aggregation. Blood 2011;118(11):3129–3136.
98. Hunter RW, Mackintosh C, Hers I., Protein kinase C-mediated phosphorylation and activation of PDE3A regulate cAMP levels in human platelets. J Biol Chem 2009;284(18):12339–12348.
99. Lang F, Munzer P, Gawaz M, Borst O., Regulation of STIM1/Orai1-dependent Ca2+ signalling in platelets. Thromb Haemost 2013;110(5):925–930.
100. Lewandrowski U, Wortelkamp S, Lohrig K, Zahedi RP, Wolters DA, Walter U, et al. Platelet membrane proteomics: A novel repository for functional research. Blood 2009;114(1):e10–9.
101. Li Z, Delaney MK, O’Brien KA, Du X., Signaling during platelet adhesion and activation. Arterioscler Thromb Vasc Biol 2010;30(12):2341–2349.
102. Niu H, Chen X, Gruppo RA, Li D, Wang Y, Zhang L, et al. Integrin alphaIIb-mediated PI3K/Akt activation in platelets. PLoS One 2012;7(10):e47356.
103. Borroni B, Colciaghi F, Caltagirone C, Rozzini L, Broglio L, Cattabeni F, et al. Platelet amyloid precursor protein abnormalities in mild cognitive impairment predict conversion to dementia of Alzheimer type: A 2-year follow-up study. Arch Neurol 2003;60(12):1740–1744.
104. Borroni B, Colciaghi F, Pastorino L, Pettenati C, Cottini E, Rozzini L, et al. Amyloid precursor protein in platelets of patients with Alzheimer disease: Effect of acetylcholinesterase inhibitor treatment. Arch Neurol 2001;58(3):442–446.
105. Casoli T, Di Stefano G, Balietti M, Solazzi M, Giorgetti B, Fattoretti P., Peripheral inflammatory biomarkers of Alzheimer’s disease: The role of platelets. Biogerontology 2010;11(5):627–633.
106. Catricala S, Torti M, Ricevuti G., Alzheimer disease and platelets: How’s that relevant. Immun Ageing 2012;9(1):20.
107. Evin G, Li QX., Platelets and Alzheimer’s disease: Potential of APP as a biomarker. World J Psychiatry 2012;2(6):102–113.
108. Veitinger M, Varga B, Guterres SB, Zellner M., Platelets, a reliable source for peripheral Alzheimer’s disease biomarkers? Acta Neuropathol Commun 2014;2:65.
109. Berk M, Plein H, Ferreira D., Platelet glutamate receptor supersensitivity in major depressive disorder. Clin Neuropharmacol 2001;24(3):129–132.
110. Das I, Khan NS, Puri BK, Sooranna SR, de Belleroche J, Hirsch SR., Elevated platelet calcium mobilization and nitric oxide synthase activity may reflect abnormalities in schizophrenic brain. Biochem Biophys Res Commun 1995;212(2):375–380.
111. Vignini A, Sartini D, Morganti S, Nanetti L, Luzzi S, Provinciali L, et al. Platelet amyloid precursor protein isoform expression in Alzheimer’s disease: Evidence for peripheral marker. Int J Immunopathol Pharmacol 2011;24:529–534. Italy.
112. Tang K, Hynan LS, Baskin F, Rosenberg RN., Platelet amyloid precursor protein processing: A bio-marker for Alzheimer’s disease. J Neurol Sci 2006;240(1–2):53–58.
113. Borroni B, Agosti C, Marcello E, Di Luca M, Padovani A., Blood cell markers in Alzheimer Disease: Amyloid Precursor Protein form ratio in platelets. Exp Gerontol 2010;45(1):53–56.
114. Zimmermann M, Borroni B, Cattabeni F, Padovani A, Di Luca M., Cholinesterase inhibitors influence APP metabolism in Alzheimer disease patients. Neurobiol Dis 2005;19(1–2):237–242.
115. Skop BP, Brown TM., Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors. Psychosomatics 1996;37(1):12–16.
116. Karege F, Widmer J, Bovier P, Gaillard JM., Platelet serotonin and plasma tryptophan in depressed patients: Effect of drug treatment and clinical outcome. Neuropsychopharmacology 1994;10(3):207–214.
117. Marcolin MA, Davis JM., Platelet monoamine oxidase in schizophrenia: A meta-analysis. Schizophr Res 1992;7(3):249–267.
118. Rosado JA, Sage SO., The ERK cascade, a new pathway involved in the activation of store-mediated calcium entry in human platelets. Trends Cardiovasc Med 2002;12(5):229–234.
119. Janusonis S., Serotonin dynamics in and around the central nervous system: Is autism solvable without fundamental insights? Int J Dev Neurosci 2014;39:9–15.
120. Gabriele S, Sacco R, Persico AM., Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis. Eur Neuropsychopharmacol 2014;24(6):919–929.
121. McBride PA, Anderson GM, Hertzig ME, Snow ME, Thompson SM, Khait VD, et al. Effects of diagnosis, race, and puberty on platelet serotonin levels in autism and mental retardation. J Am Acad Child Adolesc Psychiatry 1998;37(7):767–776.
122. Pagan C, Delorme R, Callebert J, Goubran-Botros H, Amsellem F, Drouot X, et al. The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders. Transl Psychiatry 2014;4:e479.
123. Azmitia EC, Singh JS, Whitaker-Azmitia PM., Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors. Neuropharmacology 2011;60(7–8):1347–1354.
124. Adamsen D, Ramaekers V, Ho HT, Britschgi C, Rufenacht V, Meili D, et al. Autism spectrum disorder associated with low serotonin in CSF and mutations in the SLC29A4 plasma membrane monoamine transporter (PMAT) gene. Mol Autism 2014;5:43.
125. Marazziti D, Muratori F, Cesari A, Masala I, Baroni S, Giannaccini G, et al. Increased density of the platelet serotonin transporter in autism. Pharmacopsychiatry 2000;33(5):165–168.
126. Goldani AA, Downs SR, Widjaja F, Lawton B, Hendren RL., Biomarkers in autism. Front Psychiatry 2014;5:100.
127. Bijl N, Thys C, Wittevrongel C, De la Marche W, Devriendt K, Peeters H, et al. Platelet studies in autism spectrum disorder patients and first-degree relatives. Mol Autism 2015;6:57.
128. Cecchetti L, Tolley ND, Michetti N, Bury L, Weyrich AS, Gresele P., Megakaryocytes differentially sort mRNAs for matrix metalloproteinases and their inhibitors into platelets: A mechanism for regulating synthetic events. Blood 2011;118(7):1903–1911.
129. Patel SR, Hartwig JH, Italiano JE, Jr. The biogenesis of platelets from megakaryocyte proplatelets. J Clin Invest 2005;115(12):3348–3354.
130. Dictenberg JB, Swanger SA, Antar LN, Singer RH, Bassell GJ., A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. Dev Cell 2008;14(6):926–939.
131. Ferrari F, Mercaldo V, Piccoli G, Sala C, Cannata S, Achsel T, et al. The fragile X mental retardation protein-RNP granules show an mGluR-dependent localization in the post-synaptic spines. Mol Cell Neurosci 2007;34(3):343–354.
132. Feng Y, Absher D, Eberhart DE, Brown V, Malter HE, Warren ST., FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association. Mol Cell 1997;1(1):109–118.
133. Eberhart DE, Malter HE, Feng Y, Warren ST., The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals. Hum Mol Genet 1996;5(8):1083–1091.
134. Khandjian EW, Corbin F, Woerly S, Rousseau F., The fragile X mental retardation protein is associated with ribosomes. Nat Genet 1996;12(1):91–93.
135. Feng Y, Gutekunst CA, Eberhart DE, Yi H, Warren ST, Hersch SM., Fragile X mental retardation protein: Nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J Neurosci 1997;17(5):1539–1547.
136. Zimmerman GA, Weyrich AS., Signal-dependent protein synthesis by activated platelets: New pathways to altered phenotype and function. Arterioscler Thromb Vasc Biol 2008;28(3):s17–24.
137. Stefani G, Fraser CE, Darnell JC, Darnell RB., Fragile X mental retardation protein is associated with translating polyribosomes in neuronal cells. J Neurosci 2004;24(33):7272–7276.
138. Siomi MC, Zhang Y, Siomi H, Dreyfuss G., Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them. Mol Cell Biol 1996;16(7):3825–3832.
139. Weyrich AS, Schwertz H, Kraiss LW, Zimmerman GA., Protein synthesis by platelets: Historical and new perspectives. J Thromb Haemost 2009;7(2):241–246.
140. Valverde R, Pozdnyakova I, Kajander T, Venkatraman J, Regan L., Fragile X mental retardation syndrome: Structure of the KH1-KH2 domains of fragile X mental retardation protein. Structure 2007;15(9):1090–1098.
141. Vasilyev N, Polonskaia A, Darnell JC, Darnell RB, Patel DJ, Serganov A., Crystal structure reveals specific recognition of a G-quadruplex RNA by a beta-turn in the RGG motif of FMRP. Proc Natl Acad Sci USA 2015;112(39):E5391–E5400.
142. Lin KH, Lu WJ, Wang SH, Fong TH, Chou DS, Chang CC, et al. Characteristics of endogenous gamma-aminobutyric acid (GABA) in human platelets: Functional studies of a novel collagen glycoprotein VI inhibitor. J Mol Med (Berl) 2014;92(6):603–614.
143. Garcia A, Quinton TM, Dorsam RT, Kunapuli SP., Src family kinase-mediated and Erk-mediated thromboxane A2 generation are essential for VWF/GPIb-induced fibrinogen receptor activation in human platelets. Blood 2005;106(10):3410–3414.
144. Li Z, Xi X, Du X., A mitogen-activated protein kinase-dependent signaling pathway in the activation of platelet integrin alpha IIbbeta3. J Biol Chem 2001;276(45):42226–42232.
145. Zucker MB, Nachmias VT. Platelet activation. Arteriosclerosis 1985;5(1):2–18.
146. Smolenski A., Novel roles of cAMP/cGMP-dependent signaling in platelets. J Thromb Haemost 2012;10(2):167–176.
147. Berry-Kravis E, Ciurlionis R., Overexpression of fragile X gene (FMR-1) transcripts increases cAMP production in neural cells. J Neurosci Res 1998;51(1):41–48.
148. Dziembowska M, Pretto DI, Janusz A, Kaczmarek L, Leigh MJ, Gabriel N, et al. High MMP-9 activity levels in fragile X syndrome are lowered by minocycline. Am J Med Genet A 2013;161a(8):1897–1903.
149. Ronesi JA, Collins KA, Hays SA, Tsai NP, Guo W, Birnbaum SG, et al. Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome. Nat Neurosci 2012;15(3):431–440, s1.
150. Jardin I, Albarran L, Bermejo N, Salido GM, Rosado JA., Homers regulate calcium entry and aggregation in human platelets: A role for Homers in the association between STIM1 and Orai1. Biochem J 2012;445(1):29–38.
151. Willemsen R, Smits A, Mohkamsing S, Van Beerendonk H, de Haan A, de Vries B, et al. Rapid antibody test for diagnosing fragile X syndrome: A validation of the technique. Hum Genet 1997;99(3):308–311.
152. Tassone F, Hagerman RJ, Ikle DN, Dyer PN, Lampe M, Willemsen R, et al. FMRP expression as a potential prognostic indicator in fragile X syndrome. Am J Med Genet 1999;84(3):250–261.
153. Mullard A., Fragile X disappointments upset autism ambitions. Nat Rev Drug Discov 2015;14:151–153.
154. Berry-Kravis E, Sumis A, Hervey C, Nelson M, Porges SW, Weng N, et al. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr 2008;29(4):293–302.
155. Erickson CA, Weng N, Weiler IJ, Greenough WT, Stigler KA, Wink LK, et al. Open-label riluzole in fragile X syndrome. Brain Res 2011;1380:264–270.
156. Caku A, Pellerin D, Bouvier P, Riou E, Corbin F., Effect of lovastatin on behavior in children and adults with fragile X syndrome: An open-label study. Am J Med Genet A 2014;164a(11):2834–2842.
157. Westmark CJ., The quest for fragile X biomarkers. Mol Cell Pediatr 2014;1(1):1.
158. Cohen JA, Leeksma CH., Determination of the life span of human blood platelets using labelled diisopropylfluorophosphonate. J Clin Invest 1956;35(9):964–969.
159. American Psychiatric Association. Neurodevelopmental Disorders. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013. p. 31–86.
160. Buescher AV, Cidav Z, Knapp M, Mandell DS., Costs of autism spectrum disorders in the United Kingdom and the United States. JAMA Pediatr 2014;168(8):721–728.
161. de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH., Advancing the understanding of autism disease mechanisms through genetics. Nat Med 2016;22(4):345–361.
162. Provenzano G, Zunino G, Genovesi S, Sgado P, Bozzi Y., Mutant mouse models of autism spectrum disorders. Dis Markers 2012;33(5):225–239.
163. Crawley JN., Translational animal models of autism and neurodevelopmental disorders. Dialogues Clin Neurosci 2012;14(3):293–305.
164. Russell VA., Overview of animal models of attention deficit hyperactivity disorder (ADHD). Curr Protoc Neurosci 2011;Chapter 9:Unit9.35.