Making the brain glow: In vivo bioluminescence imaging to study neurodegeneration

Molecular Neurobiology

Volumn 47, Issue 3, 2013, Pages 868-882

  Hochgräfe, Katja ^a,c   Mandelkow, Eva Maria ^a,b,c  

^a GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^b CENTER OF ADVANCED EUROPEAN STUDIES AND RESEARCH CAESAR   (Germany)

^c MAX PLANCK INSTITUTE FOR NEUROLOGICAL RESEARCH   (Germany)

Author keywords

Bioluminescence imaging; Luciferase; Mouse model; Neurodegeneration

Indexed keywords

GLIAL FIBRILLARY ACIDIC PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LUCIFERASE; TOLL LIKE RECEPTOR 2; TRANSFORMING GROWTH FACTOR BETA;

ARTICLE; BIOLUMINESCENCE; BRAIN DYSFUNCTION; BRAIN INJURY; BRAIN MITOCHONDRION; ENCEPHALITIS; ENZYME SUBSTRATE; GENE EXPRESSION; IN VIVO STUDY; LONGITUDINAL STUDY; MITOCHONDRIAL TOXICITY; MOLECULAR MODEL; NERVE DEGENERATION; NERVE REGENERATION; NERVOUS SYSTEM DEVELOPMENT; NERVOUS SYSTEM INFLAMMATION; NEUROSCIENCE; NONHUMAN; TRANSGENE; ANIMAL; BRAIN; DISEASE MODEL; LUMINESCENCE; METABOLISM; METHODOLOGY; PATHOLOGY; REVIEW;

ANIMALS; BRAIN; DISEASE MODELS, ANIMAL; LUMINESCENT MEASUREMENTS; NERVE DEGENERATION; NEUROGENESIS; TRANSGENES;

EID: 84885836119     PISSN: 08937648     EISSN: 15591182     Source Type: Journal    
DOI: 10.1007/s12035-012-8379-1     Document Type: Article

References (118)

1. Massoud TF, Gambhir S.S. (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17(5):545-580. doi:10.1101/gad.1047403
2. Ewers M, Frisoni GB, Teipel S.J., Grinberg LT, Amaro E Jr, Heinsen H, Thompson PM, Hampel H (2011) Staging Alzheimer's disease progression with multimodality neuroimaging. Prog Neurobiol 95(4):535-546. doi:10.1016/j. pneurobio.2011.06.004
3. Herholz K, Ebmeier K. (2011) Clinical amyloid imaging in Alzheimer's disease. Lancet Neurol 10(7):667-670. doi:10.1016/S1474-4422(11)70123-5
4. Ono M, Saji H. (2012) Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's disease: novel PET/SPECT imaging probes for diagnosis of Alzheimer's disease. J Pharmacol Sci 118(3):338-344
5. Troy T, Jekic-McMullen D, Sambucetti L., Rice B. (2004) Quantitative comparison of the sensitivity of detection of fluorescent and bioluminescent reporters in animal models. Mol Imaging 3(1):9-23. doi:10.1162/ 153535004773861688
6. Contag CH (2007) In vivo pathology: seeing with molecular specificity and cellular resolution in the living body. Annu Rev Pathol 2:277-305. doi:10.1146/annurev.pathol.2.010506.091930
7. Keyaerts M, Remory I, Caveliers V., Breckpot K, Bos TJ, Poelaert J, Bossuyt A., Lahoutte T. (2012) Inhibition of firefly luciferase by general anesthetics: effect on in vitro and in vivo bioluminescence imaging. PLoS One 7(1):e30061. doi:10.1371/journal.pone.0030061
8. Luker KE, Luker G.D. (2008) Applications of bioluminescence imaging to antiviral research and therapy: multiple luciferase enzymes and quantitation. Antivir Res 78(3):179-187. doi:10.1016/j.antiviral.2008.01.158
9. Prescher JA, Contag C.H. (2010) Guided by the light: visualizing biomolecular processes in living animals with bioluminescence. Curr Opin Chem Biol 14(1):80-89. doi:10.1016/j.cbpa.2009.11.001
10. Virostko J, Jansen E.D. (2009) Validation of bioluminescent imaging techniques. Methods Mol Biol 574:15-23. doi:10.1007/978-1-60327-321-3-2
11. Day JC, Tisi LC, Bailey M.J. (2004) Evolution of beetle bioluminescence: the origin of beetle luciferin. Luminescence 19(1):8-20. doi:10.1002/bio.749
12. Widder EA (2010) Bioluminescence in the ocean: origins of biological, chemical, and ecological diversity. Science 328 (5979):704-708. doi:10.1126/science.1174269
13. Contag CH, Spilman SD, Contag P.R., Oshiro M., Eames B, Dennery P, Stevenson D.K., Benaron D.A. (1997) Visualizing gene expression in living mammals using a bioluminescent reporter. Photochem Photobiol 66(4):523-531
14. Marques SM, Esteves da Silva JC (2009) Firefly bioluminescence: a mechanistic approach of luciferase catalyzed reactions. IUBMB Life 61(1):6-17. doi:10.1002/iub.134
15. Tromberg BJ, Shah N, Lanning R., Cerussi A, Espinoza J, Pham T., Svaasand L, Butler J (2000) Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy. Neoplasia 2 (1-2):26-40
16. Zhao H, Doyle TC, Coquoz O, Kalish F., Rice BW, Contag C.H. (2005) Emission spectra of bioluminescent reporters and interaction with mammalian tissue determine the sensitivity of detection in vivo. J Biomed Opt 10(4):41210. doi:10.1117/1.2032388
17. Lalancette-Hebert M, Phaneuf D, Soucy G, Weng YC, Kriz J (2009) Live imaging of Toll-like receptor 2 response in cerebral ischaemia reveals a role of olfactory bulb microglia as modulators of inflammation. Brain: J Neurol 132 (Pt 4):940-954. doi:10.1093/brain/awn345
18. Virostko J, Chen Z, Fowler M., Poffenberger G, Powers AC, Jansen E.D. (2004) Factors influencing quantification of in vivo bioluminescence imaging: application to assessment of pancreatic islet transplants. Mol Imaging 3(4):333-342. doi:10.1162/1535350042973508
19. Allard M, Cote D, Davidson L., Dazai J, Henkelman R.M. (2007) Combined magnetic resonance and bioluminescence imaging of live mice. J Biomed Opt 12(3):034018. doi:10.1117/1.2745298
20. Klose AD, Beattie BJ, Dehghani H, Vider L., Le C, Ponomarev V, Blasberg R. (2010) In vivo bioluminescence tomography with a blocking-off finite-difference SP3 method and MRI/CT coregis-tration. Med Phys 37(1):329-338
21. Razansky D, Deliolanis NC, Vinegoni C, Ntziachristos V. (2012) Deep tissue optical and optoacoustic molecular imaging technologies for pre-clinical research and drug discovery. Curr Pharm Biotechnol 13(4):504-522
22. Kuo C, Coquoz O, Troy T.L., Xu H., Rice B.W. (2007) Three-dimensional reconstruction of in vivo bioluminescent sources based on multispectral imaging. J Biomed Opt 12(2):024007. doi:10.1117/1.2717898
23. Sydow A, Van der Jeugd A, Zheng F, Ahmed T, Balschun D, Petrova O, Drexler D, Zhou L, Rune G, Mandelkow E, D'Hooge R, Alzheimer C, Mandelkow EM (2011) Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic Tau mutant. J Neurosci 31(7):2511-2525. doi:10.1523/JNEUROSCI.5245-10.2011
24. Berger F, Paulmurugan R, Bhaumik S., Gambhir S.S. (2008) Uptake kinetics and biodistribution of 14C-D-luciferin-a radiolabeled substrate for the firefly luciferase catalyzed bioluminescence reaction: impact on bioluminescence based reporter gene imaging. Eur J Nucl Med Mol Imaging 35(12):2275-2285. doi:10.1007/s00259-008-0870-6
25. Lee KH, Byun SS, Paik J.Y., Lee SY, Song SH, Choe YS, Kim B.T. (2003) Cell uptake and tissue distribution of radioiodine labelled D-luciferin: implications for luciferase based gene imaging. Nucl Med Commun 24(9):1003-1009. doi:10.1097/01.mnm.0000090431.24184.49
26. Paroo Z, Bollinger RA, Braasch D.A., Richer E., Corey DR, Antich PP, Mason R.P. (2004) Validating bioluminescence imaging as a high-throughput, quantitative modality for assessing tumor burden. Mol Imaging 3(2):117-124. doi:10.1162/1535350041464865
27. Selkoe DJ (1991) The molecular pathology of Alzheimer's disease. Neuron 6(4):487-498
28. Denk F, Wade-Martins R (2009) Knock-out and transgenic mouse models of tauopathies. Neurobiol Aging 30(1):1-13. doi:10.1016/j.neurobiolaging.2007.05. 010
29. Lee VM, Kenyon TK, Trojanowski J.Q. (2005) Transgenic animal models of tauopathies. Biochim Biophys Acta 1739 (2-3):251-259. doi:10.1016/j.bbadis.2004. 06.014
30. Eckermann K, Mocanu MM, Khlistunova I, Biernat J., Nissen A, Hofmann A, Schonig K., Bujard H, Haemisch A, Mandelkow E, Zhou L, Rune G, Mandelkow EM (2007) The beta-propensity of Tau determines aggregation and synaptic loss in inducible mouse models of tauopathy. J Biol Chem 282(43):31755-31765. doi:10.1074/jbc.M705282200
31. Mocanu MM, Nissen A, Eckermann K., Khlistunova I, Biernat J, Drexler D., Petrova O, Schonig K, Bujard H, Mandelkow E, Zhou L, Rune G, Mandelkow EM (2008) The potential for beta-structure in the repeat domain of tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous Tau in inducible mouse models of tauopathy. J Neurosci 28(3):737-748. doi:10.1523/JNEUROSCI.2824-07.2008
32. Van der Jeugd A, Hochgrafe K, Ahmed T, Decker JM, Sydow A, Hofmann A, Wu D, Messing L, Balschun D, D'Hooge R, Mandelkow EM (2012) Cognitive defects are reversible in induc-ible mice expressing pro-aggregant full-length human Tau. Acta neuropathol 123(6):787-805. doi:10.1007/s00401-012-0987-3
33. Baron U, Freundlieb S, Gossen M., Bujard H. (1995) Co-regulation of two gene activities by tetracycline via a bidirectional promoter. Nucleic Acids Res 23(17):3605-3606
34. Krestel HE, Mayford M, Seeburg P.H., Sprengel R. (2001) A GFP-equipped bidirectional expression module well suited for monitoring tetracycline- regulated gene expression in mouse. Nucleic Acids Res 29(7):E39
35. Mayford M, Bach ME, Huang Y.Y., Wang L., Hawkins RD, Kandel E.R. (1996) Control of memory formation through regulated expression of a CaMKII transgene. Science 274 (5293):1678-1683
36. Gossen M, Bujard H. (2002) Studying gene function in eukaryotes by conditional gene inactivation. Annu Rev Genet 36:153-173. doi:10.1146/annurev. genet.36.041002.120114
37. Luker KE, Luker G.D. (2010) Bioluminescence imaging of reporter mice for studies of infection and inflammation. Antivir Res 86(1):93-100. doi:10.1016/j.antiviral.2010.02.002
38. Luo J, Ho P, Steinman L., Wyss-Coray T (2008) Bioluminescence in vivo imaging of autoimmune encephalomyelitis predicts disease. Journal of Neuroinflammation 5:6. doi:10.1186/1742-2094-5-6
39. Burgin KE, Waxham MN, Rickling S, Westgate S.A., Mobley WC, Kelly P.T. (1990) In situ hybridization histochemistry of Ca2+/calmodulin-dependent protein kinase in developing rat brain. J Neurosci: Off J Soc Neurosci 10(6):1788-1798
40. Crain B, Cotman C, Taylor D., Lynch G. (1973) A quantitative electron microscopic study of synaptogenesis in the dentate gyrus of the rat. Brain Res 63:195-204
41. Yamauchi T (2005) Neuronal Ca2+/calmodulin-dependent protein kinase II-discovery, progress in a quarter of a century, and perspective: implication for learning and memory. Biol Pharm Bull 28(8):1342-1354
42. Wang Y, Mandelkow E. (2012) Degradation of tau protein by autophagy and proteasomal pathways. Biochem Soc Trans 40(4):644-652. doi:10.1042/BST20120071
43. Gould SJ, Subramani S. (1988) Firefly luciferase as a tool in molecular and cell biology. Anal Biochem 175(1):5-13
44. Keller GA, Gould S, Deluca M., Subramani S. (1987) Firefly luciferase is targeted to peroxisomes in mammalian cells. Proc Natl Acad Sci U S A 84(10):3264-3268
45. Ignowski JM, Schaffer D.V. (2004) Kinetic analysis and modeling of firefly luciferase as a quantitative reporter gene in live mammalian cells. Biotechnol Bioeng 86(7):827-834. doi:10.1002/bit.20059
46. Thompson JF, Hayes LS, Lloyd D.B. (1991) Modulation of firefly luciferase stability and impact on studies of gene regulation. Gene 103(2):171-177
47. Price JC, Guan S, Burlingame A., Prusiner SB, Ghaemmaghami S. (2010) Analysis of proteome dynamics in the mouse brain. Proc Natl Acad Sci U S A 107(32):14508-14513. doi:10.1073/pnas.1006551107
48. Riond JL, Riviere J.E. (1988) Pharmacology and toxicology of doxycycline. Vet Hum Toxicol 30(5):431-443
49. Middeldorp J, Hol E.M. (2011) GFAP in health and disease. Prog Neurobiol 93(3):421-443. doi:10.1016/j.pneurobio.2011.01.005
50. Zhu L, Ramboz S, Hewitt D., Boring L, Grass DS, Purchio A.F. (2004) Non-invasive imaging of GFAP expression after neuronal damage in mice. Neurosci Lett 367(2):210-212. doi:10.1016/j.neulet.2004.06.020
51. Cho W, Hagemann TL, Johnson D.A., Johnson JA, Messing A. (2009) Dual transgenic reporter mice as a tool for monitoring expression of glial fibrillary acidic protein. J Neurochem 110(1):343-351. doi:10.1111/j.1471-4159.2009.06146. x
52. Cordeau P Jr, Lalancette-Hebert M, Weng YC, Kriz J. (2008) Live imaging of neuroinflammation reveals sex and estrogen effects on astrocyte response to ischemic injury. Stroke 39(3):935-942. doi:10.1161/STROKEAHA.107.501460
53. Maysinger D, Behrendt M, Lalancette-Hebert M, Kriz J. (2007) Real-time imaging of astrocyte response to quantum dots: in vivo screening model system for biocompatibility of nanoparticles. Nano Lett 7(8):2513-2520. doi:10.1021/nl071611t
54. Di Giorgio F.P., Carrasco MA, Siao M.C., Maniatis T., Eggan K. (2007) Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci 10(5):608-614. doi:10.1038/nn1885
55. Nagai M, Re DB, Nagata T, Chalazonitis A., Jessell TM, Wichterle H, Przedborski S. (2007) Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci 10(5):615-622. doi:10.1038/nn1876
56. Cheng C, Zochodne D.W. (2002) In vivo proliferation, migration and phenotypic changes of Schwann cells in the presence of myelinated fibers. Neuroscience 115(1):321-329
57. Keller AF, Gravel M, Kriz J. (2009) Live imaging of amyotrophic lateral sclerosis pathogenesis: disease onset is characterized by marked induction of GFAP in Schwann cells. Glia 57(10):1130-1142. doi:10.1002/glia.20836
58. Swarup V, Phaneuf D, Bareil C., Robertson J, Rouleau GA, Kriz J, Julien J.P. (2011) Pathological hallmarks of amyotrophic lateral sclerosis/ frontotemporal lobar degeneration in transgenic mice produced with TDP-43 genomic fragments. Brain: J Neurol 134 (Pt 9):2610-2626. doi:10.1093/brain/ awr159
59. Verkhratsky A, Olabarria M, Noristani H.N., Yeh CY, Rodriguez J.J. (2010) Astrocytes in Alzheimer's disease. Neurotherapeutics 7(4):399-412. doi:10.1016/j.nurt.2010.05.017
60. Balducci C, Forloni G. (2011) APP transgenic mice: their use and limitations. Neuromol Med 13(2):117-137. doi:10.1007/s12017-010-8141-7
61. Watts JC, Giles K, Grillo S.K., Lemus A., DeArmond SJ, Prusiner S.B. (2011) Bioluminescence imaging of Abeta deposition in bigenic mouse models of Alzheimer's disease. Proc Natl Acad Sci U S A 108(6):2528-2533. doi:10.1073/pnas.1019034108
62. Meyer-Luehmann M., Coomaraswamy J, Bolmont T., Kaeser S, Schaefer C, Kilger E., Neuenschwander A, Abramowski D, Frey P, Jaton AL, Vigouret JM, Paganetti P, Walsh DM, Mathews PM, Ghiso J, Staufenbiel M, Walker LC, Jucker M (2006) Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science 313(5794):1781-1784. doi:10.1126/science.1131864
63. Stohr J, Watts JC, Mensinger Z.L., Oehler A., Grillo SK, Dearmond SJ, Prusiner SB, Giles K. (2012) Purified and synthetic Alzheimer's amyloid beta (Abeta) prions. Proc Natl Acad Sci U S A 109(27):11025-11030. doi:10.1073/pnas.1206555109
64. Kovacs GG, Budka H. (2008) Prion diseases: from protein to cell pathology. Am J Pathol 172(3):555-565. doi:10.2353/ajpath.2008.070442
65. Tamguney G, Francis KP, Giles K, Lemus A., DeArmond SJ, Prusiner S.B. (2009) Measuring prions by bioluminescence imaging. Proc Natl Acad Sci U S A 106(35):15002-15006. doi:10.1073/pnas.0907339106
66. Beynon SB, Walker F.R. (2012) Microglial activation in the injured and healthy brain: what are we really talking about? Practical and theoretical issues associated with the measurement of changes in microglial morphology. Neuroscience. doi:10.1016/j.neuroscience.2012.07.029
67. Olson JK, Miller S.D. (2004) Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol 173(6):3916-3924
68. Lalancette-Hebert M., Moquin A, Choi A.O., Kriz J., Maysinger D. (2010) Lipopolysaccharide-QD micelles induce marked induction of TLR2 and lipid droplet accumulation in olfactory bulb microglia. Mol Pharm 7(4):1183-1194. doi:10.1021/mp1000372
69. Malek R, Borowicz KK, Jargiello M, Czuczwar S.J. (2007) Role of nuclear factor kappaB in the central nervous system. Pharmacol Rep 59(1):25-33
70. Memet S (2006) NF-kappaB functions in the nervous system: from development to disease. Biochem Pharmacol 72(9):1180-1195. doi:10.1016/j.bcp. 2006.09.003
71. Blackwell TS, Yull FE, Chen C.L., Venkatakrishnan A., Blackwell TR, Hicks DJ, Lancaster LH, Christman J.W., Kerr L.D. (2000) Multiorgan nuclear factor kappa B activation in a transgenic mouse model of systemic inflammation. Am J Respir Crit Care Med 162 (3 Pt 1):1095-1101
72. Carlsen H, Moskaug JO, Fromm S.H., Blomhoff R. (2002) In vivo imaging of NF-kappa B activity. J Immunol 168(3):1441-1446
73. Hubbard AK, Timblin CR, Shukla A, Rincon M., Mossman B.T. (2002) Activation of NF-kappaB-dependent gene expression by silica in lungs of luciferase reporter mice. Am J Physiol Lung Cell Mol Physiol 282(5):L968-L975. doi:10.1152/ajplung.00327.2001
74. Zangani M, Carlsen H, Kielland A., Os A, Hauglin H, Blomhoff R., Munthe LA, Bogen B (2009) Tracking early autoimmune disease by bioluminescent imaging of NF-kappaB activation reveals pathology in multiple organ systems. Am J Pathol 174(4):1358-1367. doi:10.2353/ajpath.2009.080700
75. Sadikot RT, Blackwell T.S. (2005) Bioluminescence imaging. Proc Am Thorac Soc 2(6):537-540. doi:10.1513/pats.200507-067DS, 511-532
76. Dohlen G, Carlsen H, Blomhoff R., Thaulow E, Saugstad O.D. (2005) Reoxygenation of hypoxic mice with 100 % oxygen induces brain nuclear factor-kappa B. Pediatr Res 58(5):941-945. doi:10.1203/01.PDR.0000182595.62545. EE
77. Dohlen G, Odland HH, Carlsen H, Blomhoff R., Thaulow E, Saugstad O.D. (2008) Antioxidant activity in the newborn brain: a luciferase mouse model. Neonatology 93(2):125-131. doi:10.1159/000107777
78. Gutierrez H, Davies A.M. (2011) Regulation of neural process growth, elaboration and structural plasticity by NF-kappaB. Trends Neurosci 34(6):316-325. doi:10.1016/j.tins.2011.03.001
79. Tesseur I, Wyss-Coray T (2006) A role for TGF-beta signaling in neurodegeneration: evidence from genetically engineered models. Current Alzheimer Res 3(5):505-513
80. Lin AH, Luo J, Mondshein L.H., ten Dijke P, Vivien D, Contag C.H., Wyss-Coray T (2005) Global analysis of Smad2/3-depen-dent TGF-beta signaling in living mice reveals prominent tissue-specific responses to injury. J Immunol 175(1):547-554
81. Luo J, Wyss-Coray T (2009) Bioluminescence analysis of Smad-dependent TGF-beta signaling in live mice. Methods Mol Biol 574:193-202. doi:10.1007/978-1-60327-321-3-16
82. de Heredia L.L., Gengatharan A, Foster J., Mather S, Magoulas C. (2011) Bioluminescence imaging of the brain response to acute inflammation in living C/EBP reporter mice. Neurosci Lett 497(2):134-138. doi:10.1016/j.neulet.2011.04. 046
83. Li L, Fei Z, Ren J., Sun R, Liu Z, Sheng Z., Wang L, Sun X, Yu J, Wang Z, Fei J (2008) Functional imaging of interleukin 1 beta expression in inflammatory process using bioluminescence imaging in transgenic mice. BMC Immunol 9:49. doi:10.1186/1471-2172-9-49
84. Zhao C, Deng W, Gage F.H. (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132(4):645-660. doi:10.1016/j.cell.2008.01.033
85. Couillard-Despres S., Finkl R, Winner B., Ploetz S, Wiedermann D, Aigner R., Bogdahn U, Winkler J, Hoehn M, Aigner L (2008) In vivo optical imaging of neurogenesis: watching new neurons in the intact brain. Mol Imaging 7(1):28-34
86. Villeda SA, Luo J, Mosher K.I., Zou B., Britschgi M, Bieri G, Stan T.M., Fainberg N., Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Despres S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T (2011) The ageing systemic milieu negatively regulates neuro-genesis and cognitive function. Nature 477(7362):90-94. doi:10.1038/nature10357
87. Reumers V, Deroose CM, Krylyshkina O, Nuyts J., Geraerts M, Mortelmans L, Gijsbers R., Van den Haute C, Debyser Z, Baekelandt V (2008) Noninvasive and quantitative monitoring of adult neuronal stem cell migration in mouse brain using bioluminescence imaging. Stem Cells 26(9):2382-2390. doi:10.1634/ stemcells.2007-1062
88. Reekmans KP, Praet J, De Vocht N, Tambuyzer BR, Bergwerf I, Daans J., Baekelandt V, Vanhoutte G, Goossens H, Jorens PG, Ysebaert DK, Chatterjee S, Pauwels P, Van Marck E, Berneman ZN, Van der Linden A, Ponsaerts P (2011) Clinical potential of intravenous neural stem cell delivery for treatment of neuroin-flammatory disease in mice? Cell Transplant 20(6):851-869. doi:10.3727/096368910X543411
89. Gravel M, Weng YC, Kriz J. (2011) Model system for live imaging of neuronal responses to injury and repair. Mol Imaging 10(6):434-445
90. Denny JB (2006) Molecular mechanisms, biological actions, and neuropharmacology of the growth-associated protein GAP-43. Curr Neuropharmacol 4(4):293-304
91. Lezi E, Swerdlow R.H. (2012) Mitochondria in neurodegeneration. Adv Exp Med Biol 942:269-286. doi:10.1007/978-94-007-2869-1-12
92. Lauritzen KH, Moldestad O, Eide L., Carlsen H, Nesse G, Storm J.F., Mansuy IM, Bergersen LH, Klungland A (2010) Mitochondrial DNA toxicity in forebrain neurons causes apopto-sis, neurodegeneration, and impaired behavior. Mol Cell Biol 30(6):1357-1367. doi:10.1128/MCB.01149-09
93. Lauritzen KH, Cheng C, Wiksen H., Bergersen LH, Klungland A. (2011) Mitochondrial DNA toxicity compromises mitochondrial dynamics and induces hippocampal antioxidant defenses. DNA Repair (Amst) 10(6):639-653. doi:10.1016/j.dnarep.2011.04.011
94. Close DM, Xu T, Sayler G.S., Ripp S. (2011) In vivo bioluminescent imaging (BLI): noninvasive visualization and interrogation of biological processes in living animals. Sensors (Basel) 11(1):180-206. doi:10.3390/ s110100180
95. Massoud TF, Paulmurugan R, De A., Ray P, Gambhir S.S. (2007) Reporter gene imaging of protein-protein interactions in living subjects. Curr Opin Biotechnol 18(1):31-37. doi:10.1016/j.copbio.2007.01.007
96. Villalobos V, Naik S, Piwnica-Worms D (2007) Current state of imaging protein-protein interactions in vivo with genetically encoded reporters. Annu Rev Biomed Eng 9:321-349. doi:10.1146/annurev.bioeng.9.060906.152044
97. Naik S, Piwnica-Worms D (2007) Real-time imaging of beta-catenin dynamics in cells and living mice. Proc Natl Acad Sci U S A 104(44):17465-17470. doi:10.1073/pnas.0704465104
98. Kesarwala AH, Samrakandi MM, Piwnica-Worms D (2009) Proteasome inhibition blocks ligand-induced dynamic processing and internalization of epidermal growth factor receptor via altered receptor ubiquitination and phosphorylation. Cancer Res 69(3):976-983. doi:10.1158/0008-5472.CAN-08-2938
99. Moroz E, Carlin S, Dyomina K., Burke S, Thaler HT, Blasberg R, Serganova I. (2009) Real-time imaging of HIF-1alpha stabilization and degradation. PLoS One 4(4):e5077. doi:10.1371/journal.pone.0005077
100. Ray P, Pimenta H, Paulmurugan R., Berger F, Phelps ME, Iyer M, Gambhir S.S. (2002) Noninvasive quantitative imaging of protein-protein interactions in living subjects. Proc Natl Acad Sci U S A 99(5):3105-3110. doi:10.1073/pnas. 052710999
101. Paulmurugan R, Umezawa Y, Gambhir S.S. (2002) Noninvasive imaging of protein-protein interactions in living subjects by using reporter protein complementation and reconstitution strategies. Proc Natl Acad Sci U S A 99(24):15608-15613. doi:10.1073/pnas.242594299
102. Zhang L, Lee KC, Bhojani M.S., Khan AP, Shilman A, Holland EC, Ross B.D., Rehemtulla A. (2007) Molecular imaging of Akt kinase activity. Nat Med 13(9):1114-1119. doi:10.1038/nm1608
103. Coppola JM, Ross BD, Rehemtulla A. (2008) Noninvasive imaging of apoptosis and its application in cancer therapeutics. Clin Cancer Res 14(8):2492-2501. doi:10.1158/1078-0432.CCR-07-0782
104. Hickson J, Ackler S, Klaubert D., Bouska J, Ellis P, Foster K., Oleksijew A, Rodriguez L, Schlessinger S, Wang B, Frost D (2010) Noninvasive molecular imaging of apoptosis in vivo using a modified firefly luciferase substrate, Z-DEVD-aminoluciferin. Cell Death Differ 17(6):1003-1010. doi:10.1038/cdd.2009. 205
105. Shah K, Tung CH, Breakefield X.O., Weissleder R. (2005) In vivo imaging of S-TRAIL-mediated tumor regression and apoptosis. Mol Ther 11(6):926-931. doi:10.1016/j.ymthe.2005.01.017
106. Pfleger KD, Eidne K.A. (2006) Illuminating insights into proteinprotein interactions using bioluminescence resonance energy transfer (BRET). Nat Methods 3(3):165-174. doi:10.1038/nmeth841
107. Xia Z, Rao J. (2009) Biosensing and imaging based on bioluminescence resonance energy transfer. Curr Opin Biotechnol 20(1):37-44. doi:10.1016/j.copbio.2009.01.001
108. Dragulescu-Andrasi A., Chan CT, De A, Massoud T.F., Gambhir S.S. (2011) Bioluminescence resonance energy transfer (BRET) imaging of protein-protein interactions within deep tissues of living subjects. Proc Natl Acad Sci U S A 108(29):12060-12065. doi:10.1073/pnas.1100923108
109. Loening AM, Wu AM, Gambhir S.S. (2007) Red-shifted Renilla reniformis luciferase variants for imaging in living subjects. Nat Methods 4(8):641-643. doi:10.1038/nmeth1070
110. Walls ZF, Gambhir S.S. (2008) BRET-based method for detection of specific RNA species. Bioconjug Chem 19(1):178-184. doi:10.1021/bc700278n
111. Gammon ST, Villalobos VM, Roshal M, Samrakandi M., Piwnica-Worms D (2009) Rational design of novel red-shifted BRET pairs: platforms for real-time single-chain protease biosensors. Biotechnol Prog 25(2):559-569. doi:10.1002/btpr.144
112. Gross S, Gammon ST, Moss B.L., Rauch D., Harding J, Heinecke JW, Ratner L, Piwnica-Worms D (2009) Bioluminescence imaging of myeloperoxidase activity in vivo. Nat Med 15(4):455-461. doi:10.1038/nm.1886
113. Lee D, Khaja S, Velasquez-Castano JC, Dasari M., Sun C, Petros J, Taylor W.R., Murthy N. (2007) In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles. Nat Mater 6(10):765-769. doi:10.1038/nmat1983
114. Stafford P, Abdelwahab MG, Kim do Y, Preul MC, Rho J.M., Scheck A.C. (2010) The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr Metab (Lond) 7(74). doi:10.1186/1743-7075-7-74
115. Hall DJ, Han SH, Chepetan A, Inui E.G., Rogers M., Dugan L.L. (2012) Dynamic optical imaging of metabolic and NADPH oxidase-derived superoxide in live mouse brain using fluorescence lifetime unmixing. J Cereb Blood Flow Metab 32(1):23-32. doi:10.1038/jcbfm.2011.119
116. Kundu K, Knight SF, Lee S, Taylor W.R., Murthy N. (2010) A significant improvement of the efficacy of radical oxidant probes by the kinetic isotope effect. Angew Chem 49(35):6134-6138. doi:10.1002/anie.201002228
117. Liu H, Ren G, Miao Z., Zhang X, Tang X, Han P., Gambhir SS, Cheng Z (2010) Molecular optical imaging with radioactive probes. PLoS One 5(3):e9470. doi:10.1371/journal.pone.0009470
118. Robertson R, Germanos MS, Li C, Mitchell G.S., Cherry SR, Silva M.D. (2009) Optical imaging of Cerenkov light generation from positron-emitting radiotracers. Phys Med Biol 54(16):N355-N365. doi:10.1088/0031-9155/54/16/N01