Mechanisms of chemotherapy-induced behavioral toxicities

Frontiers in Neuroscience

Volumn 9, Issue APR, 2015, Pages

  Vichaya, Elisabeth G ^a   Chiu, Gabriel S ^a   Krukowski, Karen ^a   Lacourt, Tamara E ^a   Kavelaars, Annemieke ^a   Dantzer, Robert ^a   Heijnen, Cobi J ^a   Walker, Adam K ^a,b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b MONASH UNIVERSITY   (Australia)

Author keywords

Cellular metabolism; Chemotherapy; Cognition; DAMP; Fatigue; Inflammation; Mitochondria; Neuropathy

Indexed keywords

ANTINEOPLASTIC AGENT; HIGH MOBILITY GROUP B1 PROTEIN; MITOCHONDRIAL DNA; NUCLEIC ACID; PROTEIN P53; PURINE DERIVATIVE; REACTIVE OXYGEN METABOLITE;

BEHAVIOR CHANGE; BEHAVIOR DISORDER; CANCER CHEMOTHERAPY; CANCER PATIENT; CELL METABOLISM; CHEMOTHERAPY INDUCED BEHAVIORAL TOXICITY; COGNITIVE DEFECT; DISEASE ASSOCIATION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA ADDUCT; DRUG INDUCED DISEASE; FATIGUE; HUMAN; LONG TERM SURVIVAL; MITOCHONDRION; NERVOUS SYSTEM INFLAMMATION; NEUROPATHY; OXIDATIVE STRESS; REVIEW;

EID: 84928664472     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2015.00131     Document Type: Review

References (230)

1. Adam-Vizi, V., and Chinopoulos, C. (2006). Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol. Sci. 27, 639-645. doi: 10.1016/j.tips.2006.10.005
2. Ale, A., Bruna, J., Morell, M., Van De Velde, H., Monbaliu, J., Navarro, X., et al. (2014). Treatment with anti-TNF alpha protects against the neuropathy induced by the proteasome inhibitor bortezomib in a mouse model. Exp. Neurol. 253, 165-173. doi: 10.1016/j.expneurol.2013.12.020
3. Alexandrescu, D. T., Ichim, T. E., Kabigting, F., and Dasanu, C. A. (2009). Acute gout during treatment with paclitaxel for metastatic melanoma. Rheumatology (Oxford) 48, 862-863. doi: 10.1093/rheumatology/kep123
4. Alexopoulou, L., Holt, A. C., Medzhitov, R., and Flavell, R. A. (2001). Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413, 732-738. doi: 10.1038/35099560
5. Alfano, C. M., Imayama, I., Neuhouser, M. L., Kiecolt-Glaser, J. K., Smith, A. W., Meeske, K., et al. (2012). Fatigue, inflammation, and omega-3 and omega-6 fatty acid intake among breast cancer survivors. J. Clin. Oncol. 30, 1280-1287. doi: 10.1200/JCO.2011.36.4109
6. Aluise, C. D., Sultana, R., Tangpong, J., Vore, M., St Clair, D., Moscow, J. A., et al. (2010). Chemo brain (chemo fog) as a potential side effect of doxorubicin administration: role of cytokine-induced, oxidative/nitrosative stress in cognitive dysfunction. Adv. Exp. Med. Biol. 678, 147-156. doi: 10.1007/978-1-4419-6306-2_19
7. Angulo, E., Casado, V., Mallol, J., Canela, E. I., Vinals, F., Ferrer, I., et al. (2003). A1 adenosine receptors accumulate in neurodegenerative structures in Alzheimer disease and mediate both amyloid precursor protein processing and tau phosphorylation and translocation. Brain Pathol. 13, 440-451. doi: 10.1111/j.1750-3639.2003.tb00475.x
8. Areti, A., Yerra, V. G., Naidu, V., and Kumar, A. (2014). Oxidative stress and nerve damage: role in chemotherapy induced peripheral neuropathy. Redox Biol. 2, 289-295. doi: 10.1016/j.redox.2014.01.006
9. Aymeric, L., Apetoh, L., Ghiringhelli, F., Tesniere, A., Martins, I., Kroemer, G., et al. (2010). Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity. Cancer Res. 70, 855-858. doi: 10.1158/0008-5472.CAN-09-3566
10. Barry, M. A., Behnke, C. A., and Eastman, A. (1990). Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem. Pharmacol. 40, 2353-2362. doi: 10.1016/0006-2952(90)90733-2
11. Baudino, B., D'agata, F., Caroppo, P., Castellano, G., Cauda, S., Manfredi, M., et al. (2012). The chemotherapy long-term effect on cognitive functions and brain metabolism in lymphoma patients. Q. J. Nucl. Med. Mol. Imaging 56, 559-568.
12. Becker, B. F. (1993). Towards the physiological function of uric acid. Free Radic. Biol. Med. 14, 615-631. doi: 10.1016/0891-5849(93)90143-I
13. Berger, A. M., Abernethy, A. P., Atkinson, A., Barsevick, A. M., Breitbart, W. S., Cella, D., et al. (2010). Cancer-related fatigue. J. Natl. Compr. Canc. Netw. 8, 904-931.
14. Bernard, J. J., Cowing-Zitron, C., Nakatsuji, T., Muehleisen, B., Muto, J., Borkowski, A. W., et al. (2012). Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat. Med. 18, 1286-1290. doi: 10.1038/nm.2861
15. Bock, P. R., Hanisch, J., Matthes, H., and Zanker, K. S. (2014). Targeting inflammation in cancer-related-fatigue: a rationale for mistletoe therapy as supportive care in colorectal cancer patients. Inflamm. Allergy Drug Targets 13, 105-111. doi: 10.2174/1871528113666140428103332
16. Boison, D. (2007). Adenosine as a modulator of brain activity. Drug News Perspect. 20, 607-611. doi: 10.1358/dnp.2007.20.10.1181353
17. Boison, D. (2008). Adenosine as a neuromodulator in neurological diseases. Curr. Opin. Pharmacol. 8, 2-7. doi: 10.1016/j.coph.2007.09.002
18. Bonuccelli, G., Tsirigos, A., Whitaker-Menezes, D., Pavlides, S., Pestell, R. G., Chiavarina, B., et al. (2010). Ketones and lactate "fuel" tumor growth and metastasis: evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 9, 3506-3514. doi: 10.4161/cc.9.17.12731
19. Bottiglieri, S., Tierson, N., Patel, R., Mo, J. H., and Mehdi, S. (2013). Gemcitabine-induced gouty arthritis attacks. J. Oncol. Pharm. Pract. 19, 284-288. doi: 10.1177/1078155212464893
20. Boyette-Davis, J., and Dougherty, P. M. (2011). Protection against oxaliplatin-induced mechanical hyperalgesia and intraepidermal nerve fiber loss by minocycline. Exp. Neurol. 229, 353-357. doi: 10.1016/j.expneurol.2011.02.019
21. Boyette-Davis, J., Xin, W., Zhang, H., and Dougherty, P. M. (2011). Intraepidermal nerve fiber loss corresponds to the development of taxol-induced hyperalgesia and can be prevented by treatment with minocycline. Pain 152, 308-313. doi: 10.1016/j.pain.2010.10.030
22. Bragado, P., Armesilla, A., Silva, A., and Porras, A. (2007). Apoptosis by cisplatin requires p53 mediated p38alpha MAPK activation through ROS generation. Apoptosis 12, 1733-1742. doi: 10.1007/s10495-007-0082-8
23. Briones, T. L., and Woods, J. (2014). Dysregulation in myelination mediated by persistent neuroinflammation: possible mechanisms in chemotherapy-related cognitive impairment. Brain Behav. Immun. 35, 23-32. doi: 10.1016/j.bbi.2013.07.175
24. Brown, L. F., and Kroenke, K. (2009). Cancer-related fatigue and its associations with depression and anxiety: a systematic review. Psychosomatics 50, 440-447. doi: 10.1016/S0033-3182(09)70835-7
25. Capuron, L., Gumnick, J. F., Musselman, D. L., Lawson, D. H., Reemsnyder, A., Nemeroff, C. B., et al. (2002). Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 26, 643-652. doi: 10.1016/S0893-133X(01)00407-9
26. Cardoso, S., Santos, R. X., Carvalho, C., Correia, S., Pereira, G. C., Pereira, S. S., et al. (2008). Doxorubicin increases the susceptibility of brain mitochondria to Ca(2+)-induced permeability transition and oxidative damage. Free Radic. Biol. Med. 45, 1395-1402. doi: 10.1016/j.freeradbiomed.2008.08.008
27. Castellani, P., Balza, E., and Rubartelli, A. (2014). Inflammation, DAMPs, tumor development, and progression: a vicious circle orchestrated by redox signaling. Antioxid. Redox Signal. 20, 1086-1097. doi: 10.1089/ars.2012.5164
28. Cata, J. P., Weng, H. R., and Dougherty, P. M. (2008). The effects of thalidomide and minocycline on taxol-induced hyperalgesia in rats. Brain Res. 1229, 100-110. doi: 10.1016/j.brainres.2008.07.001
29. Cavaletti, G., Alberti, P., Frigeni, B., Piatti, M., and Susani, E. (2011). Chemotherapy-induced neuropathy. Curr. Treat. Options Neurol. 13, 180-190. doi: 10.1007/s11940-010-0108-3
30. Cavaletti, G., Cavalletti, E., Oggioni, N., Sottani, C., Minoia, C., D'incalci, M., et al. (2001). Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. Neurotoxicology 21, 389-393. doi: 10.1046/j.1529-8027.2001.01008-5.x
31. Cavaletti, G., Marzorati, L., Bogliun, G., Colombo, N., Marzola, M., Pittelli, M. R., et al. (1992). Cisplatin-induced peripheral neurotoxicity is dependent on total-dose intensity and single-dose intensity. Cancer 69, 203-207.
32. Cella, D., Davis, K., Breitbart, W., Curt, G., and Fatigue, C. (2001). Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. J. Clin. Oncol. 19, 3385-3391.
33. Chance, B., Sies, H., and Boveris, A. (1979). Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59, 527-605.
34. Chaudhuri, A., and Behan, P. O. (2000). Fatigue and basal ganglia. J. Neurol. Sci. 179, 34-42. doi: 10.1016/S0022-510X(00)00411-1
35. Chavan, S. S., Huerta, P. T., Robbiati, S., Valdes-Ferrer, S. I., Ochani, M., Dancho, M., et al. (2012). HMGB1 mediates cognitive impairment in sepsis survivors. Mol. Med. 18, 930-937. doi: 10.2119/molmed.2012.00195
36. Chen, G. Y., and Nunez, G. (2010). Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol. 10, 826-837. doi: 10.1038/nri2873
37. Chen, Y., Jungsuwadee, P., Vore, M., Butterfield, D. A., and St Clair, D. K. (2007). Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues. Mol. Interv. 7, 147-156. doi: 10.1124/mi.7.3.6
38. Cherry, J. D., Olschowka, J. A., and O'banion, M. K. (2014). Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J. Neuroinflammation 11, 98. doi: 10.1186/1742-2094-11-98
39. Chiu, G. S., Chatterjee, D., Darmody, P. T., Walsh, J. P., Meling, D. D., Johnson, R. W., et al. (2012). Hypoxia/reoxygenation impairs memory formation via adenosine-dependent activation of caspase 1. J. Neurosci. 32, 13945-13955. doi: 10.1523/JNEUROSCI.0704-12.2012
40. Chiu, G. S., Darmody, P. T., Walsh, J. P., Moon, M. L., Kwakwa, K. A., Bray, J. K., et al. (2014). Adenosine through the A2A adenosine receptor increases IL-1beta in the brain contributing to anxiety. Brain Behav. Immun. 41, 218-231. doi: 10.1016/j.bbi.2014.05.018
41. Chiu, G. S., and Freund, G. G. (2014). Modulation of neuroimmunity by adenosine and its receptors: metabolism to mental illness. Metab. Clin. Exp. 63, 1491-1498. doi: 10.1016/j.metabol.2014.09.003
42. Chowdhury, S. K., Smith, D. R., and Fernyhough, P. (2013). The role of aberrant mitochondrial bioenergetics in diabetic neuropathy. Neurobiol. Dis. 51, 56-65. doi: 10.1016/j.nbd.2012.03.016
43. Circu, M. L., and Aw, T. Y. (2010). Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med. 48, 749-762. doi: 10.1016/j.freeradbiomed.2009.12.022
44. Cleeland, C. S. (2007). Symptom burden: multiple symptoms and their impact as patient-reported outcomes. J. Natl. Cancer Inst. Monographs 2007, 16-21. doi: 10.1093/jncimonographs/lgm005
45. Cleeland, C. S., Bennett, G. J., Dantzer, R., Dougherty, P. M., Dunn, A. J., Meyers, C. A., et al. (2003). Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms. Cancer 97, 2919-2925. doi: 10.1002/cncr.11382
46. Collado-Hidalgo, A., Bower, J. E., Ganz, P. A., Cole, S. W., and Irwin, M. R. (2006). Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin. Cancer Res. 12, 2759-2766. doi: 10.1158/1078-0432.CCR-05-2398
47. Cook, S. P., Vulchanova, L., Hargreaves, K. M., Elde, R., and Mccleskey, E. W. (1997). Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature 387, 505-508. doi: 10.1038/387505a0
48. Corona, C., Masciopinto, F., Silvestri, E., Viscovo, A. D., Lattanzio, R., Sorda, R. L., et al. (2010). Dietary zinc supplementation of 3xTg-AD mice increases BDNF levels and prevents cognitive deficits as well as mitochondrial dysfunction. Cell Death Dis. 1, e91. doi: 10.1038/cddis.2010.73
49. Crouser, E. D., Julian, M. W., Blaho, D. V., and Pfeiffer, D. R. (2002). Endotoxin-induced mitochondrial damage correlates with impaired respiratory activity. Crit. Care Med. 30, 276-284. doi: 10.1097/00003246-200202000-00002
50. Curt, G. A. (2000). Impact of fatigue on quality of life in oncology patients. Semin. Hematol. 37, 14-17. doi: 10.1016/S0037-1963(00)90063-5
51. Curt, G. A., Breitbart, W., Cella, D., Groopman, J. E., Horning, S. J., Itri, L. M., et al. (2000). Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition. Oncologist 5, 353-360. doi: 10.1634/theoncologist.5-5-353
52. Cutolo, M., Sulli, A., Pizzorni, C., Seriolo, B., and Straub, R. H. (2001). Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann. Rheum. Dis. 60, 729-735. doi: 10.1136/ard.60.8.729
53. Dalakas, M. C., Semino-Mora, C., and Leon-Monzon, M. (2001). Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC). Lab. Invest. 81, 1537-1544. doi: 10.1038/labinvest.3780367
54. Dall'igna, O. P., Fett, P., Gomes, M. W., Souza, D. O., Cunha, R. A., and Lara, D. R. (2007). Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice. Exp. Neurol. 203, 241-245. doi: 10.1016/j.expneurol.2006.08.008
55. Dantzer, R., Heijnen, C. J., Kavelaars, A., Laye, S., and Capuron, L. (2014). The neuroimmune basis of fatigue. Trends Neurosci. 37, 39-46. doi: 10.1016/j.tins.2013.10.003
56. Dantzer, R., Meagher, M. W., and Cleeland, C. S. (2012). Translational approaches to treatment-induced symptoms in cancer patients. Nat. Rev. Clin. Oncol. 9, 414-426. doi: 10.1038/nrclinonc.2012.88
57. D'avila, J. C., Santiago, A. P., Amancio, R. T., Galina, A., Oliveira, M. F., and Bozza, F. A. (2008). Sepsis induces brain mitochondrial dysfunction. Crit. Care Med. 36, 1925-1932. doi: 10.1097/CCM.0b013e3181760c4b
58. Davis, J. M. (1995). Central and peripheral factors in fatigue. J. Sports Sci. 13, S49-S53. doi: 10.1080/02640419508732277
59. Davis, J. M., Zhao, Z., Stock, H. S., Mehl, K. A., Buggy, J., and Hand, G. A. (2003). Central nervous system effects of caffeine and adenosine on fatigue. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284, R399-R404. doi: 10.1152/ajpregu.00386.2002
60. Di Cesare Mannelli, L., Pacini, A., Bonaccini, L., Zanardelli, M., Mello, T., and Ghelardini, C. (2013). Morphologic features and glial activation in rat oxaliplatin-dependent neuropathic pain. J. Pain 14, 1585-1600. doi: 10.1016/j.jpain.2013.08.002
61. Di Cesare Mannelli, L., Pacini, A., Micheli, L., Tani, A., Zanardelli, M., and Ghelardini, C. (2014). Glial role in oxaliplatin-induced neuropathic pain. Exp. Neurol. 261, 22-33. doi: 10.1016/j.expneurol.2014.06.016
62. Dickens, A. M., Vainio, S., Marjamaki, P., Johansson, J., Lehtiniemi, P., Rokka, J., et al. (2014). Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers 11C-(R)-PK11195 and 18F-GE-180. J. Nucl. Med. 55, 466-472. doi: 10.2967/jnumed.113.125625
63. Dienel, G. A. (2012). Brain lactate metabolism: the discoveries and the controversies. J. Cereb. Blood Flow Metab. 32, 1107-1138. doi: 10.1038/jcbfm.2011.175
64. Dina, O. A., Chen, X., Reichling, D., and Levine, J. D. (2001). Role of protein kinase Cepsilon and protein kinase A in a model of paclitaxel-induced painful peripheral neuropathy in the rat. Neuroscience 108, 507-515. doi: 10.1016/S0306-4522(01)00425-0
65. Dougherty, P. M., Cata, J. P., Cordella, J. V., Burton, A., and Weng, H. R. (2004). Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain 109, 132-142. doi: 10.1016/j.pain.2004.01.021
66. Dragicevic, N., Mamcarz, M., Zhu, Y., Buzzeo, R., Tan, J., Arendash, G. W., et al. (2010). Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer's transgenic mice. J. Alzheimers. Dis. 20(Suppl. 2), S535-S550. doi: 10.3233/JAD-2010-100342
67. Drouin-Ouellet, J., Brownell, A. L., Saint-Pierre, M., Fasano, C., Emond, V., Trudeau, L. E., et al. (2011). Neuroinflammation is associated with changes in glial mGluR5 expression and the development of neonatal excitotoxic lesions. Glia 59, 188-199. doi: 10.1002/glia.21086
68. Dulla, C., and Masino, S. (2013). "Physiologic and metabolic regulation of adenosine: mechanisms," in Adenosine, eds S. Masino and D. Boison (New York, NY: Springer), 87-107.
69. Dunwiddie, T. V., Diao, L., and Proctor, W. R. (1997). Adenine nucleotides undergo rapid, quantitative conversion to adenosine in the extracellular space in rat hippocampus. J. Neurosci. 17, 7673-7682.
70. Feldman, P., Due, M. R., Ripsch, M. S., Khanna, R., and White, F. A. (2012). The persistent release of HMGB1 contributes to tactile hyperalgesia in a rodent model of neuropathic pain. J. Neuroinflammation 9, 180. doi: 10.1186/1742-2094-9-180
71. Flanary, B. E., and Streit, W. J. (2004). Progressive telomere shortening occurs in cultured rat microglia, but not astrocytes. Glia 45, 75-88. doi: 10.1002/glia.10301
72. Florio, C., Prezioso, A., Papaioannou, A., and Vertua, R. (1998). Adenosine A1 receptors modulate anxiety in CD1 mice. Psychopharmacology (Berl). 136, 311-319. doi: 10.1007/s002130050572
73. Fuchs, S. Y., Adler, V., Pincus, M. R., and Ronai, Z. (1998). MEKK1/JNK signaling stabilizes and activates p53. Proc. Natl. Acad. Sci. U.S.A. 95, 10541-10546. doi: 10.1073/pnas.95.18.10541
74. Fukui, K., Omoi, N. O., Hayasaka, T., Shinnkai, T., Suzuki, S., Abe, K., et al. (2002). Cognitive impairment of rats caused by oxidative stress and aging, and its prevention by vitamin E. Ann. N. Y. Acad. Sci. 959, 275-284. doi: 10.1111/j.1749-6632.2002.tb02099.x
75. Gamelin, E., Gamelin, L., Bossi, L., and Quasthoff, S. (2002). Clinical aspects and molecular basis of oxaliplatin neurotoxicity: current management and development of preventive measures. Semin. Oncol. 29, 21-33. doi: 10.1053/sonc.2002.35525
76. Gan, H. K., Bernstein, L. J., Brown, J., Ringash, J., Vakilha, M., Wang, L., et al. (2011). Cognitive functioning after radiotherapy or chemoradiotherapy for head-and-neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 81, 126-134. doi: 10.1016/j.ijrobp.2010.05.004
77. Ganz, P. A., Kwan, L., Castellon, S. A., Oppenheim, A., Bower, J. E., Silverman, D. H., et al. (2013). Cognitive complaints after breast cancer treatments: examining the relationship with neuropsychological test performance. J. Natl. Cancer Inst. 105, 791-801. doi: 10.1093/jnci/djt073
78. Gasse, P., Riteau, N., Charron, S., Girre, S., Fick, L., Petrilli, V., et al. (2009). Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis. Am. J. Respir. Crit. Care Med. 179, 903-913. doi: 10.1164/rccm.200808-1274OC
79. Gehrmann, J., and Banati, R. B. (1995). Microglial turnover in the injured CNS: activated microglia undergo delayed DNA fragmentation following peripheral nerve injury. J. Neuropathol. Exp. Neurol. 54, 680-688. doi: 10.1097/00005072-199509000-00010
80. Gibbs, M. E., and Hertz, L. (2008). Inhibition of astrocytic energy metabolism by D-lactate exposure impairs memory. Neurochem. Int. 52, 1012-1018. doi: 10.1016/j.neuint.2007.10.014
81. Giurgiovich, A. J., Diwan, B. A., Lee, K. B., Anderson, L. M., Rice, J. M., and Poirier, M. C. (1996). Cisplatin-DNA adduct formation in maternal and fetal rat tissues after transplacental cisplatin exposure. Carcinogenesis 17, 1665-1669. doi: 10.1093/carcin/17.8.1665
82. Giurgiovich, A. J., Diwan, B. A., Olivero, O. A., Anderson, L. M., Rice, J. M., and Poirier, M. C. (1997). Elevated mitochondrial cisplatin-DNA adduct levels in rat tissues after transplacental cisplatin exposure. Carcinogenesis 18, 93-96. doi: 10.1093/carcin/18.1.93
83. Grothey, A., Nikcevich, D. A., Sloan, J. A., Kugler, J. W., Silberstein, P. T., Dentchev, T., et al. (2011). Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer: NCCTG N04C7. J. Clin. Oncol. 29, 421-427. doi: 10.1200/JCO.2010.31.5911
84. Grundtman, C., Bruton, J., Yamada, T., Ostberg, T., Pisetsky, D. S., Harris, H. E., et al. (2010). Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional aspects in skeletal muscles of idiopathic inflammatory myopathies. FASEB J. 24, 570-578. doi: 10.1096/fj.09-144782
85. Gu, X., Zheng, Y., Ren, B., Zhang, R., Mei, F., Zhang, J., et al. (2010). Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-alpha expression in a mouse model. Mol. Pain 6, 64. doi: 10.1186/1744-8069-6-64
86. Gwak, Y. S., Kang, J., Unabia, G. C., and Hulsebosch, C. E. (2012). Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats. Exp. Neurol. 234, 362-372. doi: 10.1016/j.expneurol.2011.10.010
87. Hartman, S. C., and Buchanan, J. M. (1959). Nucleic acids, purines, pyrimidines (nucleotide synthesis). Annu. Rev. Biochem. 28, 365-410. doi: 10.1146/annurev.bi.28.070159.002053
88. Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., et al. (2004). Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303, 1526-1529. doi: 10.1126/science.1093620
89. Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., et al. (2000). A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745. doi: 10.1038/35047123
90. Hu, D. E., Moore, A. M., Thomsen, L. L., and Brindle, K. M. (2004). Uric acid promotes tumor immune rejection. Cancer Res. 64, 5059-5062. doi: 10.1158/0008-5472.CAN-04-1586
91. Hunter, R. L., Dragicevic, N., Seifert, K., Choi, D. Y., Liu, M., Kim, H. C., et al. (2007). Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J. Neurochem. 100, 1375-1386. doi: 10.1111/j.1471-4159.2006.04327.x
92. Huston, J. P., Haas, H. L., Boix, F., Pfister, M., Decking, U., Schrader, J., et al. (1996). Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats. Neuroscience 73, 99-107. doi: 10.1016/0306-4522(96)00021-8
93. Hutchinson, A. D., Hosking, J. R., Kichenadasse, G., Mattiske, J. K., and Wilson, C. (2012). Objective and subjective cognitive impairment following chemotherapy for cancer: a systematic review. Cancer Treat. Rev. 38, 926-934. doi: 10.1016/j.ctrv.2012.05.002
94. Hwang, P. M., Bunz, F., Yu, J., Rago, C., Chan, T. A., Murphy, M. P., et al. (2001). Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in colorectal cancer cells. Nat. Med. 7, 1111-1117. doi: 10.1038/nm1001-1111
95. Illman, J., Corringham, R., Robinson, D. Jr., Davis, H. M., Rossi, J. F., Cella, D., et al. (2005). Are inflammatory cytokines the common link between cancer-associated cachexia and depression? J. Support. Oncol. 3, 37-50.
96. Innominato, P. F., Giacchetti, S., Moreau, T., Bjarnason, G. A., Smaaland, R., Focan, C., et al. (2013). Fatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancer. Cancer 119, 2564-2573. doi: 10.1002/cncr.28072
97. Inoue, K. (2002). Microglial activation by purines and pyrimidines. Glia 40, 156-163. doi: 10.1002/glia.10150
98. Ishii, K. J., and Akira, S. (2005). Innate immune recognition of nucleic acids: beyond toll-like receptors. Int. J. Cancer 117, 517-523. doi: 10.1002/ijc.21402
99. Jamieson, E. R., and Lippard, S. J. (1999). Structure, recognition, and processing of Cisplatin-DNA adducts. Chem. Rev. 99, 2467-2498. doi: 10.1021/cr980421n
100. Janelsins, M. C., Mustian, K. M., Palesh, O. G., Mohile, S. G., Peppone, L. J., Sprod, L. K., et al. (2012). Differential expression of cytokines in breast cancer patients receiving different chemotherapies: implications for cognitive impairment research. Support. Care Cancer 20, 831-839. doi: 10.1007/s00520-011-1158-0
101. Janes, K., Little, J. W., Li, C., Bryant, L., Chen, C., Chen, Z., et al. (2014a). The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1. J. Biol. Chem. 289, 21082-21097. doi: 10.1074/jbc. M114.569574
102. Janes, K., Wahlman, C., Little, J. W., Doyle, T., Tosh, D. K., Jacobson, K. A., et al. (2014b). Spinal neuroimmmune activation is independent of T-cell infiltration and attenuated by A3 adenosine receptor agonists in a model of oxaliplatin-induced peripheral neuropathy. Brain Behav. Immun. 44, 91-99. doi: 10.1016/j.bbi.2014.08.010
103. Jin, H. W., Flatters, S. J., Xiao, W. H., Mulhern, H. L., and Bennett, G. J. (2008). Prevention of paclitaxel-evoked painful peripheral neuropathy by acetyl-L-carnitine: effects on axonal mitochondria, sensory nerve fiber terminal arbors, and cutaneous Langerhans cells. Exp. Neurol. 210, 229-237. doi: 10.1016/j.expneurol.2007.11.001
104. Johnsson, A., Olsson, C., Nygren, O., Nilsson, M., Seiving, B., and Cavallin-Stahl, E. (1995). Pharmacokinetics and tissue distribution of cisplatin in nude mice: platinum levels and cisplatin-DNA adducts. Cancer Chemother. Pharmacol. 37, 23-31. doi: 10.1007/BF00685625
105. Jones, D., Vichaya, E. G., Wang, X. S., Sailors, M. H., Cleeland, C. S., and Wefel, J. S. (2013). Acute cognitive impairment in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplant. Cancer 119, 4188-4195. doi: 10.1002/cncr.28323
106. Jounai, N., Kobiyama, K., Takeshita, F., and Ishii, K. J. (2012). Recognition of damage-associated molecular patterns related to nucleic acids during inflammation and vaccination. Front. Cell. Infect. Microbiol. 2:168. doi: 10.3389/fcimb.2012.00168
107. Kaczmarek, A., Vandenabeele, P., and Krysko, D. V. (2013). Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 38, 209-223. doi: 10.1016/j.immuni.2013.02.003
108. Kennedy, G., Spence, V. A., Mclaren, M., Hill, A., Underwood, C., and Belch, J. J. (2005). Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radic. Biol. Med. 39, 584-589. doi: 10.1016/j.freeradbiomed.2005.04.020
109. Kesler, S., Janelsins, M., Koovakkattu, D., Palesh, O., Mustian, K., Morrow, G., et al. (2013). Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors. Brain Behav. Immun. 30 Suppl, S109-S116. doi: 10.1016/j.bbi.2012.05.017
110. Kim, J. H., Dougherty, P. M., and Abdi, S. (2015). Basic science and clinical management of painful and non-painful chemotherapy-related neuropathy. Gynecol. Oncol. 136, 453-459. doi: 10.1016/j.ygyno.2015.01.524
111. Kosturakis, A. K., He, Z., Li, Y., Boyette-Davis, J. A., Shah, N., Thomas, S. K., et al. (2014). Subclinical peripheral neuropathy in patients with multiple myeloma before chemotherapy is correlated with decreased fingertip innervation density. J. Clin. Oncol. 32, 3156-3162. doi: 10.1200/JCO.2013.54.5418
112. Kruidering, M., Van De Water, B., De Heer, E., Mulder, G. J., and Nagelkerke, J. F. (1997). Cisplatin-induced nephrotoxicity in porcine proximal tubular cells: mitochondrial dysfunction by inhibition of complexes I to IV of the respiratory chain. J. Pharmacol. Exp. Ther. 280, 638-649.
113. Krukowski, K., Huo, X. J., Ozcan, M., Nijboer, C. H., Heijnen, C. J., and Kavelaars, A. (2014). 109. Pifithrin-μ prevents paclitaxel-induced peripheral neuropathy in a mouse model. Brain Behav. Immun. 40(Suppl.), e32. doi: 10.1016/j.bbi.2014.06.129
114. Lassmann, H., Bancher, C., Breitschopf, H., Wegiel, J., Bobinski, M., Jellinger, K., et al. (1995). Cell death in Alzheimer's disease evaluated by DNA fragmentation in situ. Acta Neuropathol. 89, 35-41. doi: 10.1007/BF00294257
115. Lecrubier, Y. (2006). Physical components of depression and psychomotor retardation. J. Clin. Psychiatry 67(Suppl. 6), 23-26.
116. Ledeboer, A., Jekich, B. M., Sloane, E. M., Mahoney, J. H., Langer, S. J., Milligan, E. D., et al. (2007). Intrathecal interleukin-10 gene therapy attenuates paclitaxel-induced mechanical allodynia and proinflammatory cytokine expression in dorsal root ganglia in rats. Brain Behav. Immun. 21, 686-698. doi: 10.1016/j.bbi.2006.10.012
117. Leist, M., Single, B., Castoldi, A. F., Kuhnle, S., and Nicotera, P. (1997). Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J. Exp. Med. 185, 1481-1486. doi: 10.1084/jem.185.8.1481
118. Li, R. L., Zhang, Z. Z., Peng, M., Wu, Y., Zhang, J. J., Wang, C. Y., et al. (2013). Postoperative impairment of cognitive function in old mice: a possible role for neuroinflammation mediated by HMGB1, S100B, and RAGE. J. Surg. Res. 185, 815-824. doi: 10.1016/j.jss.2013.06.043
119. Liu, C. Y., Sims-Mccallum, R. P., and Schiffer, C. A. (2005). A single dose of rasburicase is sufficient for the treatment of hyperuricemia in patients receiving chemotherapy. Leuk. Res. 29, 463-465. doi: 10.1016/j.leukres.2004.09.004
120. Liu, J. (2008). The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview. Neurochem. Res. 33, 194-203. doi: 10.1007/s11064-007-9403-0
121. Liu, J., Head, E., Gharib, A. M., Yuan, W., Ingersoll, R. T., Hagen, T. M., et al. (2002). Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc. Natl. Acad. Sci. U.S.A. 99, 2356-2361. doi: 10.1073/pnas.261709299
122. Logan, A. C., and Wong, C. (2001). Chronic fatigue syndrome: oxidative stress and dietary modifications. Altern. Med. Rev. 6, 450-459.
123. Lotze, M. T., and Tracey, K. J. (2005). High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat. Rev. Immunol. 5, 331-342. doi: 10.1038/nri1594
124. Lotze, M. T., Zeh, H. J., Rubartelli, A., Sparvero, L. J., Amoscato, A. A., Washburn, N. R., et al. (2007). The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol. Rev. 220, 60-81. doi: 10.1111/j.1600-065X.2007.00579.x
125. Low, P. A., Nickander, K. K., and Tritschler, H. J. (1997). The roles of oxidative stress and antioxidant treatment in experimental diabetic neuropathy. Diabetes 46(Suppl. 2), S38-S42. doi: 10.2337/diab.46.2.S38
126. Ma, M. H., Yang, H. H., Parker, K., Manyak, S., Friedman, J. M., Altamirano, C., et al. (2003). The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. Clin. Cancer Res. 9, 1136-1144.
127. Mao-Ying, Q. L., Kavelaars, A., Krukowski, K., Huo, X. J., Zhou, W., Price, T. J., et al. (2014). The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model. PLoS ONE 9:e100701. doi: 10.1371/journal.pone.0100701
128. Marchenko, N. D., Zaika, A., and Moll, U. M. (2000). Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J. Biol. Chem. 275, 16202-16212. doi: 10.1074/jbc.275.21.16202
129. Martinon, F., Petrilli, V., Mayor, A., Tardivel, A., and Tschopp, J. (2006). Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237-241. doi: 10.1038/nature04516
130. Martins, I., Tesniere, A., Kepp, O., Michaud, M., Schlemmer, F., Senovilla, L., et al. (2009). Chemotherapy induces ATP release from tumor cells. Cell Cycle 8, 3723-3728. doi: 10.4161/cc.8.22.10026
131. Mattson, M. P. (2000). Apoptosis in neurodegenerative disorders. Nat. Rev. Mol. Cell Biol. 1, 120-129. doi: 10.1038/35040009
132. Mcdonald, E. S., Randon, K. R., Knight, A., and Windebank, A. J. (2005). Cisplatin preferentially binds to DNA in dorsal root ganglion neurons in vitro and in vivo: a potential mechanism for neurotoxicity. Neurobiol. Dis. 18, 305-313. doi: 10.1016/j.nbd.2004.09.013
133. Melli, G., Taiana, M., Camozzi, F., Triolo, D., Podini, P., Quattrini, A., et al. (2008). Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy. Exp. Neurol. 214, 276-284. doi: 10.1016/j.expneurol.2008.08.013
134. Michaud, M., Martins, I., Sukkurwala, A. Q., Adjemian, S., Ma, Y., Pellegatti, P., et al. (2011). Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 334, 1573-1577. doi: 10.1126/science.1208347
135. Mielke, S., Sparreboom, A., and Mross, K. (2006). Peripheral neuropathy: a persisting challenge in paclitaxel-based regimes. Eur. J. Cancer 42, 24-30. doi: 10.1016/j.ejca.2005.06.030
136. Mileshkin, L., Stark, R., Day, B., Seymour, J. F., Zeldis, J. B., and Prince, H. M. (2006). Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring. J. Clin. Oncol. 24, 4507-4514. doi: 10.1200/JCO.2006.05.6689
137. Miller, A. H., Ancoli-Israel, S., Bower, J. E., Capuron, L., and Irwin, M. R. (2008). Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. J. Clin. Oncol. 26, 971-982. doi: 10.1200/JCO.2007.10.7805
138. Miltenburg, N. C., and Boogerd, W. (2014). Chemotherapy-induced neuropathy: a comprehensive survey. Cancer Treat. Rev. 40, 872-882. doi: 10.1016/j.ctrv.2014.04.004
139. Mitsiades, C. S., Mcmillin, D., Kotoula, V., Poulaki, V., Mcmullan, C., Negri, J., et al. (2006). Antitumor effects of the proteasome inhibitor bortezomib in medullary and anaplastic thyroid carcinoma cells in vitro. J. Clin. Endocrinol. Metab. 91, 4013-4021. doi: 10.1210/jc.2005-2472
140. Moore, H. C., Parsons, M. W., Yue, G. H., Rybicki, L. A., and Siemionow, W. (2014). Electroencephalogram power changes as a correlate of chemotherapy-associated fatigue and cognitive dysfunction. Support. Care Cancer 22, 2127-2131. doi: 10.1007/s00520-014-2197-0
141. Murrough, J. W., Mao, X., Collins, K. A., Kelly, C., Andrade, G., Nestadt, P., et al. (2010). Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder. NMR Biomed. 23, 643-650. doi: 10.1002/nbm.1512
142. Myhill, S., Booth, N. E., and Mclaren-Howard, J. (2009). Chronic fatigue syndrome and mitochondrial dysfunction. Int. J. Clin. Exp. Med. 2, 1-16.
143. Myhill, S., Booth, N. E., and Mclaren-Howard, J. (2013). Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-a clinical audit. Int. J. Clin. Exp. Med. 6, 1-15.
144. Nagamatsu, M., Nickander, K. K., Schmelzer, J. D., Raya, A., Wittrock, D. A., Tritschler, H., et al. (1995). Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care 18, 1160-1167. doi: 10.2337/diacare.18.8.1160
145. Ness, K. K., Kaste, S. C., Zhu, L., Pui, C. H., Jeha, S., Nathan, P. C., et al. (2014). Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia. Leuk. Lymphoma. doi: 10.31.09/10428194.2014.944519. [Epub ahead of print].
146. Nijboer, C. H., Bonestroo, H. J., Zijlstra, J., Kavelaars, A., and Heijnen, C. J. (2013). Mitochondrial JNK phosphorylation as a novel therapeutic target to inhibit neuroinflammation and apoptosis after neonatal ischemic brain damage. Neurobiol. Dis. 54, 432-444. doi: 10.1016/j.nbd.2013.01.017
147. Nijboer, C. H., Heijnen, C. J., Van Der Kooij, M. A., Zijlstra, J., Van Velthoven, C. T., Culmsee, C., et al. (2011). Targeting the p53 pathway to protect the neonatal ischemic brain. Ann. Neurol. 70, 255-264. doi: 10.1002/ana.22413
148. Nijboer, C. H., Van Der Kooij, M. A., Van Bel, F., Ohl, F., Heijnen, C. J., and Kavelaars, A. (2010). Inhibition of the JNK/AP-1 pathway reduces neuronal death and improves behavioral outcome after neonatal hypoxic-ischemic brain injury. Brain Behav. Immun. 24, 812-821. doi: 10.1016/j.bbi.2009.09.008
149. Novak, C. M., Burghardt, P. R., and Levine, J. A. (2012). The use of a running wheel to measure activity in rodents: relationship to energy balance, general activity, and reward. Neurosci. Biobehav. Rev. 36, 1001-1014. doi: 10.1016/j.neubiorev.2011.12.012
150. O'farrell, E., Mackenzie, J., and Collins, B. (2013). Clearing the air: a review of our current understanding of "chemo fog." Curr. Oncol. Rep. 15, 260-269. doi: 10.1007/s11912-013-0307-7
151. Paludan, S. R., and Bowie, A. G. (2013). Immune sensing of DNA. Immunity 38, 870-880. doi: 10.1016/j.immuni.2013.05.004
152. Park, S. B., Lin, C. S., Krishnan, A. V., Goldstein, D., Friedlander, M. L., and Kiernan, M. C. (2011). Utilizing natural activity to dissect the pathophysiology of acute oxaliplatin-induced neuropathy. Exp. Neurol. 227, 120-127. doi: 10.1016/j.expneurol.2010.10.002
153. Pavlides, S., Whitaker-Menezes, D., Castello-Cros, R., Flomenberg, N., Witkiewicz, A. K., Frank, P. G., et al. (2009). The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 8, 3984-4001. doi: 10.4161/cc.8.23.10238
154. Peixoto, R. D., Cossetti, R., Lim, H., Cheung, W. Y., and Kennecke, H. (2014). Acute gout episodes during treatment with capecitabine: a case report. Gastrointest. Cancer Res. 7, 59-60.
155. Pertl, M. M., Hevey, D., Boyle, N. T., Hughes, M. M., Collier, S., O'dwyer, A. M., et al. (2013). C-reactive protein predicts fatigue independently of depression in breast cancer patients prior to chemotherapy. Brain Behav. Immun. 34, 108-119. doi: 10.1016/j.bbi.2013.07.177
156. Pevida, M., Lastra, A., Hidalgo, A., Baamonde, A., and Menendez, L. (2013). Spinal CCL2 and microglial activation are involved in paclitaxel-evoked cold hyperalgesia. Brain Res. Bull. 95, 21-27. doi: 10.1016/j.brainresbull.2013.03.005
157. Podratz, J. L., Knight, A. M., Ta, L. E., Staff, N. P., Gass, J. M., Genelin, K., et al. (2011). Cisplatin induced mitochondrial DNA damage in dorsal root ganglion neurons. Neurobiol. Dis. 41, 661-668. doi: 10.1016/j.nbd.2010.11.017
158. Polomano, R. C., and Bennett, G. J. (2001). Chemotherapy-evoked painful peripheral neuropathy. Pain Med. 2, 8-14. doi: 10.1046/j.1526-4637.2001.002001008.x
159. Pomykala, K. L., Ganz, P. A., Bower, J. E., Kwan, L., Castellon, S. A., Mallam, S., et al. (2013). The association between pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints following adjuvant chemotherapy for breast cancer. Brain Imaging Behav. 7, 511-523. doi: 10.1007/s11682-013-9243-2
160. Porkka-Heiskanen, T., Strecker, R. E., Thakkar, M., Bjorkum, A. A., Greene, R. W., and Mccarley, R. W. (1997). Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276, 1265-1268. doi: 10.1126/science.276.5316.1265
161. Prabakaran, S., Swatton, J. E., Ryan, M. M., Huffaker, S. J., Huang, J. T., Griffin, J. L., et al. (2004). Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol. Psychiatry 9, 684-697, 643. doi: 10.1038/sj.mp.4001532
162. Pradere, J. P., Dapito, D. H., and Schwabe, R. F. (2014). The Yin and Yang of Toll-like receptors in cancer. Oncogene 33, 3485-3495. doi: 10.1038/onc.2013.302
163. Pratico, D., Clark, C. M., Liun, F., Rokach, J., Lee, V. Y., and Trojanowski, J. Q. (2002). Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch. Neurol. 59, 972-976. doi: 10.1001/archneur.59.6.972
164. Pritchard, D. M., Watson, A. J., Potten, C. S., Jackman, A. L., and Hickman, J. A. (1997). Inhibition by uridine but not thymidine of p53-dependent intestinal apoptosis initiated by 5-fluorouracil: evidence for the involvement of RNA perturbation. Proc. Natl. Acad. Sci. U.S.A. 94, 1795-1799. doi: 10.1073/pnas.94.5.1795
165. Prue, G., Rankin, J., Allen, J., Gracey, J., and Cramp, F. (2006). Cancer-related fatigue: a critical appraisal. Eur. J. Cancer 42, 846-863. doi: 10.1016/j.ejca.2005.11.026
166. Quiroz, J. A., Gray, N. A., Kato, T., and Manji, H. K. (2008). Mitochondrially mediated plasticity in the pathophysiology and treatment of bipolar disorder. Neuropsychopharmacology 33, 2551-2565. doi: 10.1038/sj.npp.1301671
167. Rassendren, F., and Ulmann, L. (2014). "P2X Receptors and Pain," in Pathologies of Calcium Channels, eds N. Weiss and A. Koschak. Berlin; Heidelberg: Springer), 615-633.
168. Reinertsen, K. V., Grenaker Alnaes, G. I., Landmark-Hoyvik, H., Loge, J. H., Wist, E., Kristensen, V. N., et al. (2011). Fatigued breast cancer survivors and gene polymorphisms in the inflammatory pathway. Brain Behav. Immun. 25, 1376-1383. doi: 10.1016/j.bbi.2011.04.001
169. Rezin, G. T., Amboni, G., Zugno, A. I., Quevedo, J., and Streck, E. L. (2009). Mitochondrial dysfunction and psychiatric disorders. Neurochem. Res. 34, 1021-1029. doi: 10.1007/s11064-008-9865-8
170. Robinson, C. R., Zhang, H., and Dougherty, P. M. (2014). Astrocytes, but not microglia, are activated in oxaliplatin and bortezomib-induced peripheral neuropathy in the rat. Neuroscience 274, 308-317. doi: 10.1016/j.neuroscience.2014.05.051
171. Roelcke, U., Kappos, L., Lechner-Scott, J., Brunnschweiler, H., Huber, S., Ammann, W., et al. (1997). Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology 48, 1566-1571. doi: 10.1212/WNL.48.6.1566
172. Rossignol, D. A., and Frye, R. E. (2012). Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol. Psychiatry 17, 290-314. doi: 10.1038/mp.2010.136
173. Rowinsky, E. K., Chaudhry, V., Cornblath, D. R., and Donehower, R. C. (1993a). Neurotoxicity of Taxol. J. Natl. Cancer Inst. Monographs 1993, 107-115.
174. Rowinsky, E. K., Eisenhauer, E. A., Chaudhry, V., Arbuck, S. G., and Donehower, R. C. (1993b). Clinical toxicities encountered with paclitaxel (Taxol). Semin. Oncol. 20, 1-15.
175. Rubartelli, A., and Lotze, M. T. (2007). Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox. Trends Immunol. 28, 429-436. doi: 10.1016/j.it.2007.08.004
176. Sadler, I. J., Jacobsen, P. B., Booth-Jones, M., Belanger, H., Weitzner, M. A., and Fields, K. K. (2002). Preliminary evaluation of a clinical syndrome approach to assessing cancer-related fatigue. J. Pain Symptom Manage. 23, 406-416. doi: 10.1016/S0885-3924(02)00388-3
177. Sarges, R., Howard, H. R., Browne, R. G., Lebel, L. A., Seymour, P. A., and Koe, B. K. (1990). 4-Amino[1,2,4]triazolo[4,3-a]quinoxalines. A novel class of potent adenosine receptor antagonists and potential rapid-onset antidepressants. J. Med. Chem. 33, 2240-2254. doi: 10.1021/jm00170a031
178. Sauerbeck, A., Gao, J., Readnower, R., Liu, M., Pauly, J. R., Bing, G., et al. (2011). Pioglitazone attenuates mitochondrial dysfunction, cognitive impairment, cortical tissue loss, and inflammation following traumatic brain injury. Exp. Neurol. 227, 128-135. doi: 10.1016/j.expneurol.2010.10.003
179. Schaefer, L. (2014). Complexity of danger: the diverse nature of damage-associated molecular patterns. J. Biol. Chem. 289, 35237-35245. doi: 10.1074/jbc. R114.619304
180. Schafers, M., and Sorkin, L. (2008). Effect of cytokines on neuronal excitability. Neurosci. Lett. 437, 188-193. doi: 10.1016/j.neulet.2008.03.052
181. Schumacher, H. R., Taylor, W., Edwards, L., Grainger, R., Schlesinger, N., Dalbeth, N., et al. (2009). Outcome domains for studies of acute and chronic gout. J. Rheumatol. 36, 2342-2345. doi: 10.3899/jrheum.090370
182. Schwarzschild, M. A., Agnati, L., Fuxe, K., Chen, J. F., and Morelli, M. (2006). Targeting adenosine A2A receptors in Parkinson's disease. Trends Neurosci. 29, 647-654. doi: 10.1016/j.tins.2006.09.004
183. Seigers, R., Schagen, S. B., Van Tellingen, O., and Dietrich, J. (2013). Chemotherapy-related cognitive dysfunction: current animal studies and future directions. Brain Imaging Behav. 7, 453-459. doi: 10.1007/s11682-013-9250-3
184. Seigers, R., Timmermans, J., Van Der Horn, H. J., De Vries, E. F., Dierckx, R. A., Visser, L., et al. (2010). Methotrexate reduces hippocampal blood vessel density and activates microglia in rats but does not elevate central cytokine release. Behav. Brain Res. 207, 265-272. doi: 10.1016/j.bbr.2009.10.009
185. Seretny, M., Currie, G. L., Sena, E. S., Ramnarine, S., Grant, R., Macleod, M. R., et al. (2014). Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain 155, 2461-2470. doi: 10.1016/j.pain.2014.09.020
186. Sheng, R., Xu, X., Tang, Q., Bian, D., Li, Y., Qian, C., et al. (2011). Polysaccharide of radix pseudostellariae improves chronic fatigue syndrome induced by poly I:C in mice. Evid. Based Complement. Alternat. Med. 2011, 840516. doi: 10.1093/ecam/nep208
187. Shibasaki, M., Sasaki, M., Miura, M., Mizukoshi, K., Ueno, H., Hashimoto, S., et al. (2010). Induction of high mobility group box-1 in dorsal root ganglion contributes to pain hypersensitivity after peripheral nerve injury. Pain 149, 514-521. doi: 10.1016/j.pain.2010.03.023
188. Smith, L. B., Leo, M. C., Anderson, C., Wright, T. J., Weymann, K. B., and Wood, L. J. (2014). The role of IL-1beta and TNF-alpha signaling in the genesis of cancer treatment related symptoms (CTRS): a study using cytokine receptor-deficient mice. Brain Behav. Immun. 38, 66-76. doi: 10.1016/j.bbi.2013.12.022
189. Srinivasan, S., Stevens, M., and Wiley, J. W. (2000). Diabetic peripheral neuropathy: evidence for apoptosis and associated mitochondrial dysfunction. Diabetes 49, 1932-1938. doi: 10.2337/diabetes.49.11.1932
190. Stadelmann, C., Bruck, W., Bancher, C., Jellinger, K., and Lassmann, H. (1998). Alzheimer disease: DNA fragmentation indicates increased neuronal vulnerability, but not apoptosis. J. Neuropathol. Exp. Neurol. 57, 456-464. doi: 10.1097/00005072-199805000-00009
191. Suzuki, A., Stern, S. A., Bozdagi, O., Huntley, G. W., Walker, R. H., Magistretti, P. J., et al. (2011). Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144, 810-823. doi: 10.1016/j.cell.2011.02.018
192. Tan, G., Heqing, L., Jiangbo, C., Ming, J., Yanhong, M., Xianghe, L., et al. (2002). Apoptosis induced by low-dose paclitaxel is associated with p53 upregulation in nasopharyngeal carcinoma cells. Int. J. Cancer 97, 168-172. doi: 10.1002/ijc.1591
193. Tanaka, M., and Watanabe, Y. (2008). Reduced energy utilization in the brain is a feature of an animal model of fatigue. Int. J. Neurosci. 118, 683-692. doi: 10.1080/00207450701242974
194. Tang, D., Kang, R., Cheh, C. W., Livesey, K. M., Liang, X., Schapiro, N. E., et al. (2010). HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene 29, 5299-5310. doi: 10.1038/onc.2010.261
195. Tang, F., Lane, S., Korsak, A., Paton, J. F., Gourine, A. V., Kasparov, S., et al. (2014). Lactate-mediated glia-neuronal signalling in the mammalian brain. Nat. Commun. 5, 3284. doi: 10.1038/ncomms4284
196. Tangpong, J., Cole, M. P., Sultana, R., Joshi, G., Estus, S., Vore, M., et al. (2006). Adriamycin-induced, TNF-alpha-mediated central nervous system toxicity. Neurobiol. Dis. 23, 127-139. doi: 10.1016/j.nbd.2006.02.013
197. Tominaga, M., Wada, M., and Masu, M. (2001). Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia. Proc. Natl. Acad. Sci. U.S.A. 98, 6951-6956. doi: 10.1073/pnas.111025298
198. Topp, K. S., Tanner, K. D., and Levine, J. D. (2000). Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat. J. Comp. Neurol. 424, 563-576. doi: 10.1002/1096-9861(20000904)424:4<563::AID-CNE1>3.0.CO;2-U
199. Troncoso, J. C., Sukhov, R. R., Kawas, C. H., and Koliatsos, V. E. (1996). In situ labeling of dying cortical neurons in normal aging and in Alzheimer's disease: correlations with senile plaques and disease progression. J. Neuropathol. Exp. Neurol. 55, 1134-1142. doi: 10.1097/00005072-199611000-00004
200. Tuppen, H. A. L., Blakely, E. L., Turnbull, D. M., and Taylor, R. W. (2010). Mitochondrial DNA mutations and human disease. Biochim. Biophys. Acta Bioenerg. 1797, 113-128. doi: 10.1016/j.bbabio.2009.09.005
201. Uhm, J. H., and Yung, W. K. (1999). Neurologic complications of cancer therapy. Curr. Treat. Options Neurol. 1, 428-437. doi: 10.1007/s11940-996-0006-x
202. Vacas, S., Degos, V., Tracey, K. J., and Maze, M. (2014). High-mobility group box 1 protein initiates postoperative cognitive decline by engaging bone marrow-derived macrophages. Anesthesiology 120, 1160-1167. doi: 10.1097/ALN.0000000000000045
203. Valcour, V., and Shiramizu, B. (2004). HIV-associated dementia, mitochondrial dysfunction, and oxidative stress. Mitochondrion 4, 119-129. doi: 10.1016/j.mito.2004.05.009
204. Van Belle, S., Paridaens, R., Evers, G., Kerger, J., Bron, D., Foubert, J., et al. (2005). Comparison of proposed diagnostic criteria with FACT-F and VAS for cancer-related fatigue: proposal for use as a screening tool. Support. Care Cancer 13, 246-254. doi: 10.1007/s00520-004-0734-y
205. Vichaya, E. G., Wang, X. S., Boyette-Davis, J. A., Mendoza, T. R., He, Z., Thomas, S. K., et al. (2013). Subclinical pretreatment sensory deficits appear to predict the development of pain and numbness in patients with multiple myeloma undergoing chemotherapy. Cancer Chemother. Pharmacol. 71, 1531-1540. doi: 10.1007/s00280-013-2152-7
206. Vincent, A. M., Russell, J. W., Low, P., and Feldman, E. L. (2004). Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr. Rev. 25, 612-628. doi: 10.1210/er.2003-0019
207. Visser, M. R., and Smets, E. M. (1998). Fatigue, depression and quality of life in cancer patients: how are they related? Support. Care Cancer 6, 101-108. doi: 10.1007/s005200050142
208. Walker, A. K., Kavelaars, A., Heijnen, C. J., and Dantzer, R. (2014). Neuroinflammation and comorbidity of pain and depression. Pharmacol. Rev. 66, 80-101. doi: 10.1124/pr.113.008144
209. Wallace, D. C. (2005). A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu. Rev. Genet. 39, 359-407. doi: 10.1146/annurev.genet.39.110304.095751
210. Wang, J., Markesbery, W. R., and Lovell, M. A. (2006). Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment. J. Neurochem. 96, 825-832. doi: 10.1111/j.1471-4159.2005.03615.x
211. Wang, X. S., Williams, L. A., Krishnan, S., Liao, Z., Liu, P., Mao, L., et al. (2012). Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy. Brain Behav. Immun. 26, 699-705. doi: 10.1016/j.bbi.2011.12.007
212. Waseem, M., and Parvez, S. (2013). Mitochondrial dysfunction mediated cisplatin induced toxicity: modulatory role of curcumin. Food Chem. Toxicol. 53, 334-342. doi: 10.1016/j.fct.2012.11.055
213. Wedding, U., Koch, A., Rohrig, B., Pientka, L., Sauer, H., Hoffken, K., et al. (2007). Requestioning depression in patients with cancer: contribution of somatic and affective symptoms to Beck's Depression Inventory. Ann. Oncol. 18, 1875-1881. doi: 10.1093/annonc/mdm353
214. Welty-Wolf, K. E., Simonson, S. G., Huang, Y. C., Fracica, P. J., Patterson, J. W., and Piantadosi, C. A. (1996). Ultrastructural changes in skeletal muscle mitochondria in gram-negative sepsis. Shock 5, 378-384. doi: 10.1097/00024382-199605000-00011
215. Weymann, K. B., Wood, L. J., Zhu, X., and Marks, D. L. (2014). A role for orexin in cytotoxic chemotherapy-induced fatigue. Brain Behav. Immun. 37, 84-94. doi: 10.1016/j.bbi.2013.11.003
216. White, F. A., Sun, J., Waters, S. M., Ma, C., Ren, D., Ripsch, M., et al. (2005). Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion. Proc. Natl. Acad. Sci. U.S.A. 102, 14092-14097. doi: 10.1073/pnas.0503496102
217. Wieseler-Frank, J., Maier, S. F., and Watkins, L. R. (2005). Immune-to-brain communication dynamically modulates pain: physiological and pathological consequences. Brain Behav. Immun. 19, 104-111. doi: 10.1016/j.bbi.2004.08.004
218. Windebank, A. J., and Grisold, W. (2008). Chemotherapy-induced neuropathy. J. Peripher. Nerv. Syst. 13, 27-46. doi: 10.1111/j.1529-8027.2008.00156.x
219. Wolf, S., Barton, D., Kottschade, L., Grothey, A., and Loprinzi, C. (2008). Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. Eur. J. Cancer 44, 1507-1515. doi: 10.1016/j.ejca.2008.04.018
220. Wood, L. J., Nail, L. M., Perrin, N. A., Elsea, C. R., Fischer, A., and Druker, B. J. (2006). The cancer chemotherapy drug etoposide (VP-16) induces proinflammatory cytokine production and sickness behavior-like symptoms in a mouse model of cancer chemotherapy-related symptoms. Biol. Res. Nurs. 8, 157-169. doi: 10.1177/1099800406290932
221. Xiao, W. H., Zheng, H., Zheng, F. Y., Nuydens, R., Meert, T. F., and Bennett, G. J. (2011). Mitochondrial abnormality in sensory, but not motor, axons in paclitaxel-evoked painful peripheral neuropathy in the rat. Neuroscience 199, 461-469. doi: 10.1016/j.neuroscience.2011.10.010
222. Xie, Z., Smith, C. J., and Van Eldik, L. J. (2004). Activated glia induce neuron death via MAP kinase signaling pathways involving JNK and p38. Glia 45, 170-179. doi: 10.1002/glia.10314
223. Yang, Z., Schumaker, L. M., Egorin, M. J., Zuhowski, E. G., Guo, Z., and Cullen, K. J. (2006). Cisplatin preferentially binds mitochondrial DNA and voltage-dependent anion channel protein in the mitochondrial membrane of head and neck squamous cell carcinoma: possible role in apoptosis. Clin. Cancer Res. 12, 5817-5825. doi: 10.1158/1078-0432.CCR-06-1037
224. Yasuda, K., Yu, P., Kirschning, C. J., Schlatter, B., Schmitz, F., Heit, A., et al. (2005). Endosomal translocation of vertebrate DNA activates dendritic cells via TLR9-dependent and -independent pathways. J. Immunol. 174, 6129-6136. doi: 10.4049/jimmunol.174.10.6129
225. Young, L. T. (2007). Is bipolar disorder a mitochondrial disease? J. Psychiatry Neurosci. 32, 160-161.
226. Zhang, H., Boyette-Davis, J. A., Kosturakis, A. K., Li, Y., Yoon, S. Y., Walters, E. T., et al. (2013). Induction of monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 in primary sensory neurons contributes to paclitaxel-induced peripheral neuropathy. J. Pain 14, 1031-1044. doi: 10.1016/j.jpain.2013.03.012
227. Zhang, H., Yoon, S. Y., Zhang, H., and Dougherty, P. M. (2012). Evidence that spinal astrocytes but not microglia contribute to the pathogenesis of Paclitaxel-induced painful neuropathy. J. Pain 13, 293-303. doi: 10.1016/j.jpain.2011.12.002
228. Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., et al. (2010). Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464, 104-107. doi: 10.1038/nature08780
229. Zheng, H., Xiao, W. H., and Bennett, G. J. (2011). Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy. Exp. Neurol. 232, 154-161. doi: 10.1016/j.expneurol.2011.08.016
230. Zheng, H., Xiao, W. H., and Bennett, G. J. (2012). Mitotoxicity and bortezomib-induced chronic painful peripheral neuropathy. Exp. Neurol. 238, 225-234. doi: 10.1016/j.expneurol.2012.08.023