Modulation of actin dynamics by Rac1 to target cognitive function

Journal of Neurochemistry

Volumn 133, Issue 6, 2015, Pages 767-779

  Tejada Simon, Maria V ^a,b  

^a UNIVERSITY OF HOUSTON   (United States)

^b University of Houston   (United States)

Author keywords

autism; cognitive disorders; fragile X syndrome; small GTPase inhibitors

Indexed keywords

2 (MORPHOLIN 4 YLMETHYL) 5 [5 [7 (TRIFLUOROMETHYL)QUINOLIN 4 YL]SULFANYLPENTOXY]PYRAN 4 ONE; 4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE; 4 N (9 ETHYLCARBAZOL 3 YL) 2 N,N (3 MORPHOLIN 4 ULPROPYL)PYRIMIDINE 2,4 DIAMINE; ACTIN; HYDROLASE INHIBITOR; N2,N4 BIS(2 METHYL 1H INDOL 5 YL)PYRIMIDINE 2,4 DIAMINE; RAC1 PROTEIN; UNCLASSIFIED DRUG;

ACTIN FILAMENT; COGNITION; DEGENERATIVE DISEASE; DENDRITIC SPINE; DRUG STRUCTURE; FRAGILE X SYNDROME; HUMAN; LONG TERM DEPRESSION; LONG TERM POTENTIATION; MEMORY CONSOLIDATION; MENTAL DEFICIENCY; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PRIORITY JOURNAL; REVIEW; SPINAL CORD INJURY; ANIMAL; BRAIN; GROWTH, DEVELOPMENT AND AGING; MENTAL DISEASE; METABOLISM; PHYSIOLOGY;

ACTINS; ANIMALS; BRAIN; COGNITION; HUMANS; MENTAL DISORDERS; NEUROGENESIS; RAC1 GTP-BINDING PROTEIN;

EID: 84930941334     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.13100     Document Type: Review

References (135)

1. Akbar H., Cancelas J., Williams D. A., Zheng J., and, Zheng Y., (2006) Rational design and applications of a Rac GTPase-specific small molecule inhibitor. Methods Enzymol. 406, 554-565.
2. Aman M. G., Hollway J. A., Leone S., Masty J., Lindsay R., Nash P., and, Arnol E., (2009) Effects of risperidone on cognitive-motor performance and motor movements in chronically medicated children. Res. Dev. Disabil. 30, 386-396.
3. Baier A., Ndoh V. N., Lacy P., and, Eitzen G., (2014). Rac1 and Rac2 control distinct events during antigen-stimulated mast cell exocytosis. J. Leukoc. Biol. 95, 763-774.
4. Bakker C. E., de Diego Otero Y., Bontekoe C., Raghoe P., Lutejin T., Hoogeveen A. T., Oostra B. A., and, Willemsen R., (2000) Immunocytochemical and biochemical characterization of FMRP, FXR1P, and FXR2P in the mouse. Exp. Cell Res. 258, 162-170.
5. Barnes N. Y., Shi J., Yajima H., Thinakaran G., and, Parent A. T., (2008) Steady-state increase of cAMP-response element binding protein, Rac, and PAK signaling in presenilin-deficient neurons. J. Neurochem. 104, 1637-1648.
6. Belichenko P. V., and, Dahlström A., (1995) Confocal laser scanning microscopy and 3-D reconstructions of neuronal structures in human brain cortex. NeuroImage 2, 201-2017.
7. Belichenko P. V., Sourander P., Malmgren K., Nordborg C., von Essen C., Rydenhag B., Lindström S., Hedström A., Uvebrant P., and, Dahlström A., (1994a) Dendritic morphology in epileptogenic cortex from TRPE patients, revealed by intracellular Lucifer Yellow microinjection and confocal laser scanning microscopy. Epilepsy Res. 18, 233-247.
8. Belichenko P. V., Oldfors A., Hagberg B., and, Dahlström A., (1994b) Rett syndrome: 3-D confocal microscopy of cortical pyramidal dendrites and afferents. NeuroReport 5, 1509-1513.
9. Benvenuto A., Battan B., Porfirio M. C., and, Curatolo P., (2013) Pharmacotherapy of autism spectrum disorders. Brain Dev. 35, 119-127.
10. Berry-Kravis E., (2002) Epilepsia in fragile X syndrome. Dev. Med. Child Neurol. 44, 724-728.
11. Blanpied T. A., and, Ehlers M. D., (2004) Microanatomy of dendritic spines: emerging principles of synaptic pathology in psychiatric and neurological disease. Biol. Psychiatry 55, 1121-1127.
12. Blumcke I., Zuschratter W., Schewe J. C., Suter B., Lie A. A., Riederer B. M., Meyer B., Schramm J., Elger C. E., and, Wiestler O. D., (1999) Cellular pathology of hilar neurons in ammon's horn sclerosis. J. Comp. Neurol. 414, 437-453.
13. Boguski M. S., and, McCormick F., (1993) Proteins regulating Ras and its relatives. Nature 366, 643-655.
14. Bongmba O. Y. N., Martinez L. A., Elhardt M. E., Butler K., and, Tejada-Simon M. V., (2011). Modulation of dendritic spine and synaptic function by Rac1: a possible link to Fragile X syndrome pathology. Brain Res. 1399, 79-95. [Corrigendum Brain Res.,1423:114-115.]
15. Brown V., Jin P., Ceman S., et al,. (2001). Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107, 477-487.
16. von Campe G., Spencer D. D., and, Lanerolle N. C., (1997) Morphology of dentate granule cells in the human epileptogenic hippocampus. Hippocampus 7, 472-488.
17. Chen H. J., Rojas-Soto M., Oguni A., and, Kennedy M. B., (1998) A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II. Neuron 20, 895-904.
18. Comery T. A., Harris J. B., Willems P. J., Oostra B. A., Irwin S. A., Weiler I. J., and, Greenough W. T., (1997) Abnormal dendritic spines in fragile X knockout mice. Maturation and pruning deficits. Proc. Natl Acad. Sci. USA 94, 5401-5404.
19. De Rubeis S., Pasciuto E., Li K. W., et al,. (2013) CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation. Neuron 79, 1169-1182.
20. DeGeer J., and, Lamarche-Vane N., (2013) Rho GTPases in neurodegeneration diseases. Exp. Cell Res. 319, 2384-2394.
21. DeSantiago J., Bare D. J., Xiao L., Ke Y., Solaro R. J., and, Banach K., (2014) P21-activated kinase 1 (Pak1) is a negative regulator of NADPH-oxidase 2 in ventricular myocytes. J. Mol. Cell. Cardiol. 67, 77-85.
22. Desire L., Bourdin J., Loiseau N., et al,. (2005) Rac1 inhibition targets amyloid precursor protein processing by γ-secretase and decreases Aβ production in vitro and in vivo. J. Biol. Chem. 280, 37516-37525.
23. Dharmawardhane S., Hernandez E., and, Vlaar C., (2013) Development of EHop-016: a small molecule inhibitor of Rac. Enzymes 33, 117-146.
24. Dierkes R., Warnking K., Liedmann S., Seyer R., Ludwig S., and, Ehrhardt C., (2014) The Rac1 inhibitor NSC23766 exerts anti-influenza virus properties by affecting the viral polymerase complex activity. PLoS One 9, e88520.
25. Ding Z. B., Wu P., Luo Y. X., Shi H. S., Shen H. W., Wang S. J., and, Lu L., (2013) Region-specific role of Rac in nucleus accumbens core and basolateral amygdala in consolidation and reconsolidation of cocaine-associated cue memory in rats. Psychopharmacology (Berl.) 228, 427-437.
26. Dipaolo B. C., Davidovich N., Kazanietz M. G., and, Margulies S. S., (2013) Rac1 pathway mediates stretch responses in pulmonary alveolar epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 305, L141-L153.
27. Dolen G., Osterweil E., Rao B. S., Smith G. B., Auerbach B. D., Chattarji S., and, Bear M. F., (2007) Correction of fragile X syndrome in mice. Neuron 56, 955-962.
28. Duffney L. J., Wei J., Cheng J., Liu W., Smith K. R., Kittler J. T., and, Yan Z., (2013) Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism. J. Neurosci. 33, 15767-15778.
29. Ferrer I., Guionnet N., Cruz-Sanchez F., and, Tunon T., (1990) Neuronal alterations in patients with dementia: a Golgi study on biopsy samples. Neurosci. Lett. 114, 11-16.
30. Ferri N., Corsini A., Bottino P., Clerici F., and, Contini A., (2009) Virtual screening approach for the identification of new Rac1 inhibitors. J. Med. Chem. 52, 4087-4090.
31. Freiman T. M., Eismann-Schweimier J., and, Froscher M., (2011) Granule cell dispersion in temporal lobe epilepsy is associated with changes in dendritic orientation and spine distribution. Exp. Neurol. 229, 332-338.
32. Galvez R., and, Greenough W. T., (2005) Sequence of abnormal dendritic spine development in primary somatosensory cortex of a mouse model of the fragile X mental retardation syndrome. Am. J. Med. Genet. A 135, 155-160.
33. Gao Y., Xing J., Streuli M., Leto T. L., and, Zheng Y., (2001) Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors. J. Biol. Chem. 276, 47530-47541.
34. Gao Y., Dickerson J. B., Guo F., Zheng J., and, Zheng Y., (2004) Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad. Sci. USA 101, 7618-7623.
35. Garey L. J., Ong W. Y., Patel T. S., Kanani M., Davis A., Mortimer A. M., et al,. (1998) Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J. Neurol. Neurosurg. Psychiatry 65, 446-453.
36. Glantz L. A., and, Lewis D. A., (2000) Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch. Gen. Psychiatry 57, 65-73.
37. Glausier J. R., and, Lewis D. A., (2013) Dendritic spine pathology in schizophrenia. Neuroscience 251, 90-107.
38. Golden S. A., Christoffel D. J., Heshmati M., et al,. (2013) Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression. Nat. Med. 19, 337-344.
39. Haditsch U., Leone D. P., Farinelli M., Chrostek-Grashoff A., Brakebusch C., Mansuy I. M., McConnell S. K., and, Palmer T. D., (2009) A central role for the small GTPase Rac1 in hippocampal plasticity and spatial learning and memory. Mol. Cell Neurosci. 41, 409-419.
40. Haditsch U., Anderson M. P., Freewoman J., Cord B., Babu H., Brakebusch C., and, Palmer T. D., (2013) Neuronal Rac1 is required for learning-evoked neurogenesis. J. Neurosci. 33, 12229-12241.
41. Hagerman R. J., (2002). Physical and Behavioral Phenotype, in Fragile X syndrome: diagnosis, treatment and Research, 3rd edn (, Baltimore M. D., ed.), pp. 3-109. The Johns Hopkins University Press, Baltimore, Maryland.
42. Hagerman R. J., and, Cronister A., (1996). Fragile X syndrome: Diagnosis, Treatment, and Research. 2nd Ed. Johns Hopkins University Press, Baltimore.
43. Hall A., (1998) Rho GTPases and the actin cytoskeleton. Science 279, 509-514.
44. Hall A., (2005) Rho GTPases and the control of cell behavior. Biochem. Soc. Trans. 33, 891-895.
45. Harwood A., and, Braga V. M. M., (2003) Cdc42 and GSK-3: signals at the crossroads. Nat. Cell Biol. 5, 275-277.
46. Hayashi M. L., Rao B. S., Seo J. S., choi H. S., Dolan B. M., Choi S. Y., Chattarji S., and, Tonegawa S., (2007). Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc. Natl Acad. Sci. USA 104, 11489-11494.
47. Hayashi-Takagi A., Takaki M., Graziane N. M., et al,. (2010) Disrupted-in-Schizophrenia-1 (DISC1) regulates spines of the glutamate synapse via Rac1. Nat. Neurosci. 13, 327-332.
48. Hernandez E., De la Mota-Peynado A., Dharmawardhane S., and, Vloaar C. P., (2010) Novel inhibitors of Rac1 in metastatic breast cancer. P. R. Health Sci. J. 29, 348-356.
49. Higashi Y., Murayama S., Pentchev P. G., and, Suzuki K., (1993) Cerebellar degeneration in the Niemann-Pick type C mouse. Acta Neuropathol. 85, 175-184.
50. Hinterleitner C., Huelsenbeck J., Henninger C., Wartlick F., Schorr A., Kaina B., and, Fritz G., (2013) Rac1 signaling protects monocytic AML cells expressing the MLL-AF9 oncogene from caspase-mediated apoptotic death. Apoptosis 18, 963-979.
51. Hinton V. J., Brown W. T., Wisniewski K., and, Rudelli R. D., (1991) Analysis of neocortex in three males with the fragile X syndrome. Am. J. Med. Genet. 41, 289-294.
52. Hirshberg M., Stockley R. W., Dodson G., and, Webb M. R., (1997) The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue. Nat. Struct. Biol. 4, 147-152.
53. Hofbauer S. W., Krenn P. W., Ganghammer S., et al,. (2014) Tiam1/Rac1 signals contribute to the proliferation and chemoresistance, but not motility, of chronic lymphocytic leukemia cells. Blood 123, 2181-2188.
54. Huttenlocher P. R., (1970) Dendritic development and mental defect. Neurology 20, 381.
55. Huttenlocher P. R., (1991) Dendritic and synaptic pathology in mental retardation. Pediatr. Neurol. 7, 79-85.
56. Hwaiz R., Rahman M., Zhang E., and, Thorlacius H., (2014) Rac1 regulates platelet shedding of CD40L in abdominal sepsis. Lab. Invest. 94, 1054-1063.
57. Irwin S. A., Galvez R., and, Greenough W. T., (2000) Dendritic spine structural anomalies in fragile X mental retardation syndrome. Cereb. Cortex 10, 1038-1044.
58. Irwin S. A., Patel B., Idupulapati M., et al,. (2001) Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile X syndrome: a quantitative examination. Am. J. Med. Genet. 98, 161-167.
59. Isokawa M., and, Levesque M. F., (1991) Increased NMDA responses and dendritic degeneration in human epileptic hippocampal neurons in slices. Neurosci. Lett. 132, 212-216.
60. Jin P., and, Warren S. T., (2000) Understanding the molecular basis of fragile X syndrome. Hum. Mol. Genet. 9, 901-908.
61. Jin P., and, Warren S. T., (2003) New insights into fragile X syndrome: from molecules to neurobehaviors. Trends Biochem. Sci. 28, 152-158.
62. Katz E., Sims A. H., Sproul D., Caldwell H., Dixon M. J., Meehan R. R., and, Harrison D. J., (2012) Targeting of Rac GTPases blocks the spread of intact human breast cancer. Oncotarget 3, 608-619.
63. Kaufmann W. E., and, Moser H. W., (2000) Dendritic anomalies in disorders associated with mental retardation. Cereb. Cortex 10, 981-991.
64. Kawakami-Mori F., Shimosawa T., Mu S., Wang H., Ogura S., Yatomi Y., and, Fujita T., (2012) NADPH oxidase-mediated Rac1 GTP activity is necessary for nongenomic actions of the mineralocorticoid receptor in the CA1 region of the rat hippocampus. Am. J. Physiol. Endocrinol. Metab. 302.
65. Kawarazaki W., Magase M., Yoshida S., Takeuchi M., Ishizawa K., Ayuzawa N., Ueda K., and, Fujita T., (2012) Angiotensin II-and salt-induced kidney injury through Rac1-mediated mineralcorticoid receptor activation. J. Am. Soc. Nephrol. 23, 997-1007.
66. Kiao J., and, Ye Z., (2014) Delayed treatment with NSC23766 in streptozotocin-induced diabetic rats ameliorates post-ischemic neuronal apoptosis through suppression of mitochondrial p53 translocation. Neuropharmacology 85, 508-516.
67. Kim I. H., Park S. K., Hong S. T., et al,. (2009) Inositol 1,4,5-trisphosphate 3-kinase a functions as a scaffold for synaptic Rac signaling. J. Neurosci. 29, 14039-14049.
68. Kim S. du, An J. M., Lee H. G., Seo S. R., Kim S. S., Kim J. Y., Kang J. W., Bae Y. S., and, Seo J. T., (2013) Activation of Rac1-dependent redox signaling is critically involved in staurosporine-induced neurite outgrowth in PC12 cells. Free Radic. Res. 47, 95-103.
69. Levay M., Krobert K. A., Wittig K., Voigt N., Bermudez M., Wolber G., Dobrev D., Levy F. O., and, Wieland T., (2013) NSC23766, a widely used inhibitor of Rac1 activation, additionally acts as a competitive antagonist at muscarinic acetylcholine receptors. J. Pharmacol. Exp. Ther. 347, 69-79.
70. Liu Z. H., Chuang D. M., and, Smith C. B., (2011). Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int. J. Neuropsychopharmacol. 14, 618-630.
71. Liu L., Zhang H., Shi L., Zhang W., Yuan J., Chen X., Liu J., Zhang Y., and, Wang Z., (2014) Inhibition of Rac1 activity induces G1/S phase arrest through the GSK3/cyclin D1 pathway in human cancer cells. Oncol. Rep. 32, 1395-1400.
72. Ma Q. L., Yang F., Calon F., Ubeda O. J., Hansen J. E., Weisbart R. H., Beech W., Frautschy S. A., and, Cole G. M., (2008) p21-activated kinase-aberrant activation and translocation in Alzheimer disease pathogenesis. J. Biol. Chem. 283, 14132-14143.
73. Machado-Salas J. P., (1984) Abnormal dendritic patterns and aberrant spine development in Bourneville's disease-a Golgi survey. Clin. Neuropathol. 3, 52-58.
74. Marin-Padilla M., (1974) Structural organization of the cerebral cortex (motor area) in human chromosomal aberrations. A Golgi study. I. D1 (13-15) trisomy Patau syndrome. Brain Res. 60, 375-391.
75. Marin-Padilla M., (1976) Pyramidal cell abnormalities in the motor cortex of a child with Down's syndrome. A Golgi study. J. Comp. Neurol. 167, 63-81.
76. Martin H., Mali R. S., Ma P., et al,. (2013) Pak and Rac GTPases promote oncogenic KIT-induced neoplasms. J. Clin. Invest. 123, 4449-4463.
77. Martinez L. A., and, Tejada-Simon M. V., (2011) Pharmacological inactivation of the small GTPase Rac1 impairs long-term plasticity in the mouse hippocampus. Neuropharmacology 61, 305-312.
78. Martinez L. A., Klann E., and, Tejada-Simon M. V., (2007) Translocation and activation of Rac in the hippocampus during associative contextual fear learning. Neurobiol. Learn. Mem. 88, 104-113.
79. McKinney B. C., Grossman A. W., Elisseou N. M., and, Greenough W. T., (2005) Dendritic spine abnormalities in the occipital cortex of C57BL/6 Fmr1 knockout mice. Am. J. Med. Genet. B Neuropsychiatr. Genet. 136, 98-102.
80. Menna E., Disanza A., Cagnoli C., et al,. (2009) Eps8 regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF). PLoS Biol. 7.
81. Minobe S., Sakakibara A., Ohdachi T., et al,. (2009) Rac is involved in the interkinetic nuclear migration of cortical progenitor cells. Neurosci. Res. 63, 294-301.
82. Miyashiro K. Y., Beckel-Mitchener A., Purk T. P., Becker K. G., Barret T., Liu L., Carbonetto S., Weiler I. J., Greenough W. T., and, Eberwine J., (2003) RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 37, 417-431.
83. Montalvo-Ortiz B. L., Castillo-Pichardo L., Hernandez E., Humphries-Bickley T., De la Mota-Peynado A., Cubano L. A., Vlaar C. P., and, Dharmawardhane S., (2012) Characterization of EHop-016, novel small molecule inhibitor of Rac GTPase. J. Biol. Chem. 287, 13228-13238.
84. Nara A., Aki T., Funakoshi T., Unuma K., and, Uemura K., (2012) Hyperstimulation of micropinocytosis leads to lysosomal dysfunction during exposure to methamphetamine in SH-SY5Y cells. Brain Res. 1466, 1-14.
85. Newey S. E., Velamoor V., Govek W.-E., Van Aelst L., et al,. (2005) Rho GTPases, dendritic structure, and mental retardation. J. Neurobiol. 64, 58-74.
86. Nicola C., Lala P. K., and, Chakraborty C., (2008) Prostaglandin E2- mediated migration of human trophoblast requires Rac1 and Cdc42. Biol. Reprod. 78, 976-982.
87. Nithianantharajah J., and, Hannan A. J., (2013) Dysregulation of synaptic proteins, dendritic spine abnormalities and pathological plasticity of synapses as experience-dependent mediators of cognitive and psychiatric symptoms in Huntington's disease. Neuroscience 251, 66-74.
88. O'Donnell W. T., and, Warren S. T., (2002) A decade of molecular studies of fragile X syndrome. Annu. Rev. Neurosci. 25, 315-338.
89. Onesto C., Shutes A., Picard V., Schweighoffer F., and, Der C. J., (2008) Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. Methods in Enzymology 439, 111-129.
90. Penzes P., Johnson R. C., Kambampati V., Mains R. E., and, Eipper B. A., (2001) Distinct roles for the two Rho GDP/GTP exchange factor domains of kalirin in regulation of neurite growth and neuronal morphology. J. Neurosci. 21, 8426-8434.
91. Penzes P., Cahill M. E., Jones K. A., VanLeeuwen J. E., and, Woolfrey K. M., (2011) Dendritic spine pathology in neuropsychiatric disorders. Nat. Neurosci. 14, 285-293.
92. Pozueta J., Lefort R., and, Shelanski M. L., (2013) Synaptic changes in Alzheimer's disease and its models. Neuroscience 251, 51-65.
93. Rahman A., Davis B., Lovdahl C., Hanumaiah V. T., Feil R., Brakebush C., and, Arner A., (2014) The small GTPase Rac1 is required for smooth muscle contraction. J. Physiol. 592, 915-926.
94. Raynaud F., Moutin E., Schmidt S., Dahl J., Bertaso F., Boeckers T. M., Homburger V., and, Fagni L., (2014) Rho-GTPase-activating protein interacting with Cdc-42-interacting protein 4 homolog 2 (Rich2): a new Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase-activating protein that controls dendritic spine morphogenesis. J. Biol. Chem. 289, 2600-2609.
95. Raz L., Zhang Q. G., Zhou C. F., Han D., Gulati P., Yang L. C., Yang F., Wang R. M., and, Brann D. W., (2010) Role of Rac1 GTPase in NADPH oxidase activation and cognitive impairment following cerebral ischemia in the rat. PLoS One 5.
96. Reif K., and, Cantrell D. A., (1998) Networking Rho family GTPases in lymphocytes. Immunity 8, 395-401.
97. Ridley A. J., (1995) Rac and Bcr regulated phagocytic boxes. Curr. Biol. 5, 710-712.
98. Ridley A. J., (1996) Rho: theme and variations. Curr. Biol. 6, 1256-1264.
99. Roberts R. C., Conley R., Kung L., Peretti F. J., and, Chute D. J., (1996) Reduced striatal spine size in schizophrenia: a postmortem ultrastructural study. NeuroReport 7, 1214-1218.
100. Rochfort K. D., Collins L. E., Murphy R. P., and, Cummin P. M., (2014) Downregulation of blood-brain barrier phenotype by proinflammatory cytokines involves NADPH oxidase, dependent ROS generation: consequences for inerendothelial adherens and tight junctions. PLoS One 9, e101815.
101. Rosenblatt A. E., Garcia M. I., Lyons L., Xie Y., Maiorino C., Désiré L., Slingerland J., and, Burnstein K. L., (2011) Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer. Endocr. Relat. Cancer 18, 207-219.
102. Rosoklija G., Toomayan G., Ellis S. P., Keilp J., Mann J. J., Lator N., et al,. (2000) Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings. Arch. Gen. Psychiatry 57, 349-356.
103. Rudelli R. D., Brown W. T., Wisniewski K., Jenkins E. C., Laure-Kamionowska M., Connell F., and, Wisniewski H. M., (1985) Adult fragile X syndrome. Clinico-neuropathologic findings. Acta Neuropathol. 67, 289-295.
104. Sananbenesi F., Fischer A., Wang X., Schrick C., Neve R., Radulovic J., and, Tsai L. H., (2007) A hippocamal Cdk5 pathway regulates extinction of contextual fear. Nat. Neurosci. 10, 1012-1019.
105. Scheibel M. E., Crandall P. H., and, Scheibel A. B., (1974) The hippocampal-dentate complex in temporal lobe epilepsy. Epilepsia 15, 55-80.
106. Shen L., Yang A., Yao P., Sun X., Chen C., Mo C., Shi L., Chen Y., and, Liu Q., (2014) Gadolinium promoted proliferation in mouse embryo fibroblast NIH3T3 cells through Rac and PI3K/Akt signaling pathways. Biometals 27, 753-762.
107. Shutes A., Onesto C., Picard V., Leblond B., Schweighoffer F., and, Der C. J., (2007) Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. J. Biol. Chem. 282, 35666-35678.
108. Smith K. R., Davenport E. C., Wei J., Li X., Pathania M., Vaccaro V., Yan Z., and, Kittler J. T., (2014) GIT1 and βPIX link Rac1 signalling to GABAA receptor cluster stability and inhibitory synapse strength. Cell Rep. 9, 298-310.
109. Stefanini L., Boulaftali Y., Ouellette T. D., Holinstat M., Desire L., Leblond B., Andre P., Conley P. B., and, Bergmeier W., (2012) Rap1-Rac1 circuits potentiate platelet activation. Arterioscler. Thromb. Vasc. Biol. 32, 434-441.
110. Su T., Fan H. X., Jiang T., Sun W. W., Den W. Y., Gao M. M., Chen S. Q., Zhao Q. H., and, Yi Y. H., (2011) Early continuous inhibition of group 1 mGlu signaling partially rescues dendritic spine abnormalities in the Fmr1 knockout mouse model for fragile X syndrome. Psychopharmacology (Berl.) 215, 291-300.
111. Suetsugu M., and, Mehraein P., (1980) Spine distribution along the apical dendrites of the pyramidal neurons in Down's syndrome. A quantitative Golgi study. Acta Neuropathol. 50, 207-210.
112. Takashima S., Becker L. E., Armstrong D., and, Chan F. W., (1981) Abnormal neuronal development in the visual cortex of the human fetus and infant with Down's syndrome. A quantitative and qualitative Golgi study. Brain Res. 225, 1-21.
113. Takashima S., Iida K., Mito T., and, Arima M., (1994) Dendritic and histochemical development and ageing in patients with Down's syndrome. J. Intellect. Disabil. Res. 38, 265-273.
114. Tan A. M., Stamboulian S., Chang Y. W., Zhao P., Hains A. B., Waxman S. G., and, Hains B. C., (2008) Neuropathic pain memory is maintained by Rac1-regulated dendritic spine remodeling after spinal cord injury. J. Neurosci. 28, 13173-13183.
115. Tan A. M., Chang Y. W., Zhao P., Hains B. C., and, Waxman S. G., (2011) Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury. Exp. Neurol. 232, 222-233.
116. Tan A. M., Samad O. A., Liu S., Bandaru S., Zhao P., and, Waxman S. G., (2013) Burn injury-induced mechanical allodynia is maintained by Rac1-regulated dendritic spine dysgenesis. Exp. Neurol. 248, 509-519.
117. Tejada-Simon and Bongmba (2012) Regulation of neuronal morphology and plasticity by small GTP-binding proteins: implications for autism and mental retardation disorders, in Horizons Neurosci. Res. (, Andres Costa, and, Eugenio Villalba, ed.), pp. 1-67, Vol. 8, Ch.1, NOVA Sci. Pub., Hauppauge, NY.
118. Tejada-Simon M. V., Serrano F., Villasana L. E., Kanterewicz B., Wu G.-Y., Quinn M., and, Klann E., (2005) Synaptic localization of a functional NADPH oxidase in the mouse hippocampus. Mol. Cell Neurosci. 59, 97-106.
119. Tejada-Simon M. V., Villasana L. E., Serrano F., and, Klann E., (2006) NMDA Receptor activation induces translocation and activation of Rac in mouse hippocampal area CA1. Biochem. Biophys. Res. Commun. 343, 504-512.
120. Verkerk A. J. M. H., Pieretti M., Sutcliffe J. S., Fu Y. H., Kuhl D. P. A., et al,. (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65, 905-914.
121. Vojtek A. B., and, Cooper J. A., (1995) Rho family members: activators of MAP kinase cascades. Cell 82, 527-529.
122. Walkely S. U., and, Baker H. J., (1984) Sphingomyelin lipidosis in a cat: golgi studies. Acta Neuropathol. 65, 138-144.
123. Wang J., Rao Q., Wang M., et al,. (2009a) Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth. Biochem. Biophys. Res. Commun. 386, 769-774.
124. Wang P. L., Niidome T., Akaike A., Kihara T., and, Sugimoto H., (2009b) Rac1 inhibition negatively regulates transcriptional activity of the amyloid precursor protein gene. J. Neurosci. Res. 87, 2105-2114.
125. Wang Z., Sugano E., Isago H., Hiroi T., Tamai M., and, Tomita H., (2011) Differentiation of neuronal cells from NIH/3T3 fibroblasts under defined conditions. Dev. Growth Differ. 53, 357-365.
126. Wang X., Zhu H., Zhang X., Liu Y., Chen J., Medvedovic M., Li H., Weiss M. J., Ren X., and, Fan G.-C., (2012) Loss of the miR-144/451 cluster impairs ischemic preconditioning-mediated cardioprotection by targeting Rac-1. Cardiovasc. Res. 94, 379-390.
127. Wartlick F., Bopp A., Henninger C., and, Fritz G., (2013) DNA damage response (DDR) induced by topoisomerase II poisons requires nuclear function of the small GTPase Rac. Biochim. Biophys. Acta 1833, 3093-3103.
128. Wong M., and, Guo S., (2013) Dendritic spine pathology in epilepsy: cause or consequence? Neuroscience 251, 141-150.
129. Wu P., Ding Z. B., Meng S. Q., Shen H. W., Sun S. C., Luo Y. X., Liu J. F., Lu L., Zhu W. L., and, Shi J., (2014) Differential role of Rac in the basolateral amygdala and cornu ammonis 1 in the reconsolidation of auditory and contextual Pavlovian fear memory in rats. Psychopharmacology (Berl.) 231, 2909-2919.
130. Yoshida S., Ishizawa K., Ayuzawa N., Ueda K., Takeuchi M., Kawarazaki W., Fujita T., and, Nagase M., (2014). Local mineralocorticoid receptor activation and the role of Rac1 in obesity-related diabetic kidney disease. Nephron Exp. Nephrol., 126, 16-24.
131. Yu C., Zhang S., Song L., Wang Y., Hwaiz R., Luo L., and, Thorlacius H., (2014) Rac1 signaling regulates neutrophil-dependent tissue damage in experimental colitis. Eur. J. Pharmacol. 741, 90-96.
132. Zhang Q. G., Wang R., Han D., Dong Y., and, Brann D. W., (2009) Role of Rac1 GTPase in JNK signaling and neuronal cell death following global cerebral ischemia. Brain Res. 1265, 138-147.
133. Zhou Z., Hu J., Passafaro M., Xie W., and, Jia Z., (2011) GluA2 (GluR2) regulates metabotropic glutamate receptor-dependent long-term depression through N-cadherin-dependent and cofilin-mediated actin reorganization. J. Neurosci. 31, 819-833.
134. Zhu S., Lu P., Liu H., et al,. (2015) Inhibition of Rac1 activity by controlled release of NSC23766 from chitosan microspheres effectively ameliorates osteoarthritis development in vivo. Ann. Rheum. Dis. 74, 285-293.
135. Zins K., Lucas T., Reichl P., Abraham D., and, Aharinejad S., (2013) A Rac1/Cdc42 GTPase-specific small molecule inhibitor suppresses growth of primary human prostate cancer xenografts and prolongs survival in mice. PLoS One 8, e74924.