Area, age and gender dependence of the Nucleoside system in the brain: A RE of current literature

Current Topics in Medicinal Chemistry

Volumn 11, Issue 8, 2011, Pages 1012-1033

  Kovács, Zsolt ^a   Juhász, Gábor ^b   Palkovits, Miklós ^c   Dobolyi, Árpád ^c   Kékesi, Katalin A ^b  

^a UNIVERSITY OF WEST HUNGARY   (Hungary)

^b EÖTVÖS LORÁND UNIVERSITY   (Hungary)

^c INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

Author keywords

Age; And gender dependence; Area; Brain; Nucleosides

Indexed keywords

ADENOSINE A1 RECEPTOR; ADENOSINE A2 RECEPTOR; ADENOSINE DEAMINASE; ADENOSINE KINASE; BRAIN PROTEIN; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 2; GUANINE DEAMINASE; ISTRADEFYLLINE; NITROBENZYLTHIOINOSINE; NUCLEOSIDE; PURINE NUCLEOSIDE PHOSPHORYLASE;

AGE; ALZHEIMER DISEASE; ARTICLE; BASAL AMYGDALA; BRAIN REGION; BRAIN TISSUE; CAUDATE NUCLEUS; CENTRAL NERVOUS SYSTEM; CEREBELLUM CORTEX; COCHLEAR NUCLEUS; ENZYME ACTIVITY; FRONTAL CORTEX; GENDER; HUMAN; IMMUNOMODULATION; INSULA; MEDIAL GENICULATE BODY; NEUROPROTECTION; NONHUMAN; NUCLEIC ACID METABOLISM; OCCIPITAL CORTEX; PARKINSON DISEASE; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; SENILE DEMENTIA; SIGNAL TRANSDUCTION; SUBSTANTIA INNOMINATA; SUPRAOPTIC NUCLEUS; TEMPORAL CORTEX; VESTIBULAR NUCLEUS;

AGE FACTORS; ALZHEIMER DISEASE; ANIMALS; BIOLOGICAL TRANSPORT; BRAIN; FEMALE; GENE EXPRESSION; HUMANS; MALE; METABOLIC NETWORKS AND PATHWAYS; MICE; NEUROGLIA; NEURONS; NUCLEOSIDE TRANSPORT PROTEINS; NUCLEOSIDES; ORGAN SPECIFICITY; PARKINSON DISEASE; RABBITS; RATS; RECEPTORS, PURINERGIC; SCHIZOPHRENIA; SEX FACTORS; SIGNAL TRANSDUCTION;

EID: 79954489669     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802611795347636     Document Type: Article

References (290)

1. Ribeiro, J. A.; Sebastiao, A. M.; de Mendonca, A. Adenosine receptors in the nervous system: pathophysiological implications. Prog. Neurobiol., 2002, 68, 377-392.
2. Bours, M. J. L.; Swennen, E. L. R.; Di Virgilio, F.; Cronstein, B. N.; Dagnelie, P. C. Adenosine 5'-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol. Thep., 2006, 112, 358-404.
3. Burnstock, G. Historical review: ATP as a neurotransmitter. Trends Pharmacol. Sci., 2006, 27, 166-176.
4. Fields, R. D.; Burnstock, G. Purinergic signalling in neuron-glia interactions. Nat. Rev. Neurosci., 2006, 7, 423-436.
5. Jacobson, K. A.; Gao, Z. G. Adenosine receptors as therapeutic targets. Nat. Rev. Drug Discov., 2006, 5, 247-264.
6. 2A receptors and basal ganglia physiology. Prog. Neurobiol., 2007, 83, 277-292.
7. Masino, S. A.; Geiger, J. D. Are purines mediators of the anticonvulsant/ neuroprotective effects of ketogenic diets? Trends Neurosci., 2008, 31, 273-278.
8. Dip, R. G. Adenosine receptor modulation: potential implications in veterinary medicine. Vet. J. 2009, 179, 38-49.
9. Housley, G. D.; Bringmann, A.; Reichenbach, A. Purinergic signaling in special senses. Trends Neurosci., 2009, 32, 128-141.
10. Neary, J. T.; Zimmermann, H. Trophic functions of nucleotides in the central nervous system. Trends Neurosci., 2009, 32, 189-198.
11. Merighi, S.; Mirandola, P.; Varani, K.; Gessi, S.; Leung, E.; Baraldi, P. G.; Tabrizi, M. A.; Borea, P. A. A glance at adenosine receptors: novel target for antitumor therapy. Pharmacol. Ther., 2003, 100, 31-48.
12. Linden, J. Adenosine in tissue protection and tissue regeneration. Mol. Pharmacol., 2005, 67, 1385-1387.
13. Podgorska, M.; Kocbuch, K.; Pawelczyk, T. Recent advences in studies on biochemical and structural properties of equilibrative and concentrative nucleoside transporters. Acta Biochim. Pol., 2005, 52, 749-758.
14. Boison, D. Adenosine as a neuromodulator in neurological diseases. Curr. Opin. Pharmacol., 2008, 8, 2-7.
15. Burnstock, G. Purinergic signalling and disorders of the central nervous system. Nat. Rev. Drug Discov., 2008, 7, 575-590.
16. Boison, D.; Stewart, K. A. Therapeutic epilepsy research: from pharmacological rationale to focal adenosine augmentation. Biochem. Pharmacol., 2009, 78, 1428-1437.
17. De Clercq, E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int. J. Antimicrob. Agents, 2009, 33, 307-320.
18. Schmidt, A. P.; Lara, D. R.; Souza, D. O. Proposal of a guaninebased purinergic system in the mammalian central nervous system. Pharmacol. Ther., 2007, 116, 401-416.
19. Sawynok, J.; Sweeney, M. I. The role of purines in nociception. Neuroscience, 1989, 32, 557-569.
20. Connolly, G. P.; Duley, J. A. Uridine and its nucleotides: biological actions, therapeutic potentials. Trends Pharmacol. Sci., 1999, 20, 218-225.
21. Kimura, T.; Ho, I. K.; Yamamoto, I. Uridine receptor: discovery and its involvement in sleep mechanism. Sleep, 2001, 24, 251-260.
22. Vinadé, E. R.; Schmidt, A. P.; Frizzo, M. E.; Izquierdo, I.; Elisabetsky, E.; Souza, D. O. Chronically administered guanosine is anticonvulsant, amnesic and anxiolytic in mice. Brain Res., 2003, 977, 97-102.
23. Basheer, R.; Strecker, R. E.; Thakkar, M. M.; McCarley, R. W. Adenosine and sleep-wake regulation. Prog. Neurobiol., 2004, 73, 374-396.
24. Haskó, G.; Sitkovsky, M. V.; Szabó, Cs. Immunomodulatory and neuroprotective effects of inosine. Trends Pharmacol. Sci., 2004, 25, 152-157.
25. Soares, F. A.; Schmidt, A. P.; Farina, M.; Frizzo, M. E. S.; Tavares, R. G.; Portela, L. V. C.; Lara, D. R.; Souza, D. O. Anticonvulsant effect of GMP depends on its conversion to guanosine. Brain Res., 2004, 1005, 182-186.
26. Carlezon, W. A. Jr.; Mague, S. D.; Parow, A. M.; Stoll, A. L.; Cohen, B. M.; Renshaw, P. F. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol. Psychiat., 2005, 57, 343-350.
27. 2A receptor antagonists in Parkinson's disease. Pharmacol. Ther., 2005, 105, 267-310.
28. Wurtman, R. J.; Ulus, I. H.; Cansev, M.; Watkins, C. J.; Wang, L.; Marzloff, G. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res., 2006, 1088, 83-92.
29. Zhao, Q.; Shatskikh, T.; Marolewski, A.; Rusche, J. R.; Holmes, G. L. Effects of uridine on kindling. Epilepsy Behav., 2008, 13, 47-51.
30. Borst, P.; Balzarini, J.; Ono, N.; Reid, G.; de Vries, H.; Wielinga, P.; Wijnholds, J.; Zelcer, N. The potential impact of drug transporters on nucleoside-analog-based antiviral chemotherapy. Antiviral Res., 2004, 62, 1-7.
31. Sadaie, M. R.; Mayner, R.; Doniger, J. A novel approach to develop anti-HIV drugs: adapting non-nucleoside anticancer chemotherapeutics. Antiviral Res., 2004, 61, 1-18.
32. Noji, T.; Karasawa, A.; Kusaka, H. Adenosine uptake inhibitors. Eur. J. Pharmacol., 2004, 495, 1-16.
33. King, A. E.; Ackley, M. A.; Cass, C. E.; Young, J. D.; Baldwin, S. A. Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol. Sci., 2006, 27, 416-425.
34. Kowaluk, E. A.; Jarvis, M. F. Therapeutic potential of adenosine kinase inhibitors. Expert. Opin. Investig. Drugs, 2000, 9, 551-564.
35. Boison, D. Adenosine and epilepsy: from therapeutic rationale to new therapeutic strategies. Neuroscientist, 2005, 11, 25-36.
36. Boison, D. The adenosine kinase hypothesis of epileptogenesis. Prog. Neurobiol., 2008, 84, 249-262.
37. Gharib, A.; Sarda, N.; Chabannes, B.; Cronenberger, L.; Pacheco, H. The regional concentrations of S-adenosyl-L-methionine, Sadenosyl-L-homocysteine and adenosine in rat brain. J. Neurochem., 1982, 38, 810-815.
38. Delaney, S. M.; Geiger, J. D. Brain regional levels of adenosine and adenosine nucleotides in rats killed by high-energy focused microwave irradiation. J. Neurosci. Methods, 1996, 64, 151-156.
39. Kobayashi, T.; Yamada, T.; Okada, Y. The levels of adenosine and its metabolites in the guinea pig and rat brain during complete ischemia-in vivo study. Brain Res., 1998, 787, 211-219.
40. Kékesi, K. A.; Kovács, Z.; Szilágyi, N.; Bobest, M.; Szikra, T.; Dobolyi, A.; Juhász, G.; Palkovits, M. Concentration of nucleosides and related compounds in cerebral and cerebellar cortical areas and white matter of the human brain. Cell. Mol. Neurobiol., 2006, 26, 833-844.
41. Kovács, Z.; Dobolyi, A.; Juhász, G.; Kékesi, A. K. Nucleoside map of the human central nervous system. Neurochem. Res., 2010, 35, 452-464.
42. 1 receptors. Brain Res., 1996, 710, 79-91.
43. Jennings, L. L.; Hao, C.; Cabrita, M. A.; Vickers, M. F.; Baldwin, S. A.; Young, J.; Cass, C. E. Distinct regional distribution of human equilibrative nucleoside transporter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system. Neuropharmacology, 2001, 40, 722-731.
44. Pennycooke, M.; Chaudary, N.; Shuralyova, I.; Zhang, Y.; Coe, I. R. Differential expression of human nucleoside transporters in normal and tumor tissue. Biochem. Biophys. Res. Commun., 2001, 280, 951-959.
45. Ritzel, M. W. L.; Ng, A. M. L.; Yao, S. Y. M.; Graham, K.; Loewen, S. K.; Smith, K. M.; Ritzel, R. G.; Mowles, D. A.; Carpenter, P.; Chen, X. Z.; Karpinski, E.; Hyde, R. J.; Baldwin, S. A.; Cass, C. E.; Young, J. D. Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J. Biol. Chem., 2001, 276, 2914-2927.
46. Guillén-Gómez, E.; Calbet, M.; Casado, J.; de Lecea, L.; Soriano, E.; Pastor-Anglada, M.; Burgaya, F. Distribution of CNT2 and ENT1 transcripts in rat brain: selective decrease of CNT2 mRNA in the cerebral cortex of sleep-deprived rats. J. Neurochem., 2004, 90, 883-893.
47. 1 receptors in human brain: characterisation and autoradiographic visualization. Neurosci. Lett., 1986, 65, 127-132.
48. Fastbom, J.; Pazos, A.; Palacios, J. M. The distribution of adenosine A1 receptors and 5'-nucleotidase is the brain of some commonly used experimental animals. Neuroscience, 1987, 22, 813-826.
49. 2 receptor mRNA in the human brain. Neurosci. Lett., 1991, 130, 177-181.
50. Svenningsson, P.; Hall, H.; Sedvall, G.; Fredholm, B. B. Distribution of adenosine receptors in the post mortem human brain: an extended autoradiographic study. Synapse, 1997, 27, 322-335.
51. 2A receptors: an overview. Brain Res. Rev., 1999, 31, 65-82.
52. 2A receptors. Prog. Neurobiol., 1999, 59, 355-396.
53. Dawson, D. M. Absence of guanine deaminase from cerebellum. Neurology, 1971, 21, 621-626.
54. Phillips, E.; Newsholme, E. A. Maximum activities, properties and distribution of 5'-nucleotidase, adenosine kinase and adenosine deaminase in rat and human brain. J. Neurochem., 1979, 33, 553-558.
55. Broch, O. J.; Ueland, P. M. Regional and subcellular distribution of S-adenosylhomocysteine hydrolase in the adult rat brain. J. Neurochem., 1980, 35, 484-488.
56. Mackiewicz, M.; Nikonova, E. V.; Zimmermann, J. E.; Romer, M. A.; Cater, J.; Galante, R. J.; Pack, A. I. Age-related changes in adenosine metabolic enzymes in sleep/wake regulatory areas of the brain. Neurobiol. Aging, 2006, 27, 351-360.
57. Marangos, P. J.; Patel, J.; Stiver, J. Ontogeny of adenosine binding sites in rat forebrain and cerebellum. J. Neurochem., 1982, 13, 591-595.
58. Geiger, J. D.; LaBella, F. S.; Nagy, J. I. Ontogenesis of adenosine receptors in the central nervous system of the rat. Dev. Brain Res., 1984, 13, 97-104.
59. Fuchs, J. L. 5'-nucleotidase activity increases in aging rat brain. Neurobiol. Aging, 1991, 12, 523-530.
60. Lu, H.; Chen, C.; Klaassen, C. Tissue distribution of concentrative and equilibrative nucleoside transporters in male and female rats and mice. Drug Metab. Dispos., 2004, 32, 1455-1461.
61. Rucker, B.; Pereira, G. S.; Furstenau, C. R.; Izquierdo, I.; Bonan, C. D.; Sarkis, J. J. Inhibitory avoidance task reveals differences in ectonucleotidase activities between male and female rats. Neurochem. Res., 2004, 29, 2231-2237.
62. Castillo, C. A.; Albasanz, J. L.; León, D.; Jordán, J.; Pallás, M.; Camins, A.; Martín, M. Age-related expression of adenosine receptors in brain from the senescense-accerelated mouse. Exp. Gerontol., 2009, 44, 453-461.
63. Kovács, Z.; Juhász, G.; Dobolyi, A.; Bobest, M.; Papp, V.; Takáts, L.; Kékesi, K. A. Gender-and age-dependent changes in nucleoside levels in the cerebral cortex and white matter of the human brain. Brain. Res. Bull., 2010, 81, 579-584.
64. Volonté, C.; D'Ambrosi, N. Membrane compartments and purinergic signalling: the purinome, a complex interplay among ligands, degrading enzymes, receptors and transporters. FEBS J., 2009, 276, 318-329.
65. th Edition, 2006; pp 303-316.
66. Bourget, P. A.; Tremblay, G. C. Pyrimidine biosynthesis in rat brain. J. Neurochem., 1972, 19, 1617-1624.
67. Allsop, J.; Watts, R. W. E. Purine de novo synthesis in liver and developing rat brain, and the effect of some inhibitors of purine nucleotide interconversion. Enzyme, 1983, 30, 172-180.
68. Allsop, J.; Watts, R. W. Purine synthesis and salvage in brain and liver. Adv. Exp. Med. Biol., 1984, 165, 21-26.
69. Carrera, C. J.; Saven, A.; Piro, L. D. Purine metabolism of lymphocytes. Targets for chemotherapy drug development. Hematol. Oncol. Clin. North Am., 1994, 8, 357-381.
70. Zimmermann, H. 5'-Nucleotidase: Molecular structure and functional aspects. Biochem. J., 1992, 285, 345-365.
71. Brosh, S.; Zoref-Shani, E.; Danziger, E.; Bromberg, Y.; Sperling, O.; Sidi, Y. Adenine nucleotide metabolism in primary rat neuronal cultures. Int. J. Biochem. Cell Biol., 1996, 28, 319-328.
72. Barsotti, C.; Ipata, P. L. Metabolic regulation of ATP breakdown and of adenosine production in rat brain extracts. Int. J. Biochem. Cell Biol., 2004, 36, 2214-2225.
73. Dunwiddie, T. V.; Masino, S. A. The role and regulation of adenosine in the central nervous system. Annu. Rev. Neurosci., 2001, 24, 31-55.
74. Brosh, S.; Sperling, O.; Dantziger, E.; Sidi, Y. Metabolism of guanine and guanine nucleotides in primary rat neuronal cultures. J. Neurochem., 1992, 58, 1485-1490.
75. Eells, J. T.; Spector, R. Determination of ribonucleosides, deoxiribonucleosides and purine and pyrimidine bases in adult rabbit cerebrospinal fluid and plasma. Neurochem. Res., 1983, 8, 1307-1320.
76. Santos, J. N.; Hempstead, K. W.; Kopp, L. E.; Miech, R. P. Nucleotide metabolism in rat brain. J. Neurochem., 1968, 15, 367-376.
77. Barsotti, C.; Pesi, R.; Giannecchini, M.; Ipata, P. L. Evidence for the involvement of cytosolic 5'-nucleotidase (cN-II) in the synthesis of guanine nucleotides from xanthosine. J. Biol. Chem., 2005, 280, 13465-13469.
78. Betz, A. L. Identification of hypoxanthine transport and xanthine oxidase activity in brain capillaries. J. Neurochem., 1985, 44, 574-579.
79. Redzic, Z. B.; Segal, M. B.; Gasic, J. M.; Markovic, I. D.; Vojvodic, V. P.; Isakovic, A.; Thomas, S. A.; Rakic, L. M. The characteristics of nucleobase transport and metabolism by the perfused sheep choroid plexus. Brain Res., 2001, 888, 66-74.
80. Iriyama, K.; Iwamoto, T.; Yoshiura, M.; Aoki, T. Post-mortem changes in uric acid and ascorbic acid in human cerebral cortex tissues excised after cardiac death. Biochem. Med. Metab. Biol., 1986, 36, 186-193.
81. Kanemitsu, H.; Tamura, A.; Kirino, T.; Karasawa, S.; Sano, K.; Iwamoto, T.; Yosiura, M.; Iriyama, K. Xanthine and uric acid levels in rat brain following focal ischemia. J. Neurochem., 1988, 51, 1882-1885.
82. Zimmermann, H. Biochemistry, localization and functional roles of ecto-nucleotidases in the nervous system. Prog. Neurobiol., 1996, 49, 589-618.
83. Zimmermann, H. Extracellular purine metabolism. Drug. Develop. Res., 1996, 39, 337-352.
84. Yegutkin, G. G. Nucleotide-and nucleoside converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim. Biophys. Acta, 2008, 1783, 673-694.
85. Brosh, S.; Sperling, O.; Bromberg, Y.; Sidi, Y. Developmental changes in the activity of enzymes of purine metabolism in rat neuronal cells in culture and in whole brain. J. Neurochem., 1990, 54, 1776-1781.
86. Ciccarelli, R.; Ballerini, P.; Sabatino, G.; Rathbone, M. P.; D'Onofrio, M.; Caciagli, F.; Di Iorio, P. Involvement of astrocytes in purine-mediated reparative processes in the brain. Int. J. Dev. Neurosci., 2001, 19, 395-414.
87. Tremblay, G. C.; Jimenez, U.; Crandall, D. E. Pyrimidine biosynthesis and its regulation in the developing rat brain. J. Neurochem., 1976, 26, 57-64.
88. Yamada, N.; Sawasaki, Y.; Nakajima, H. Developmental changes in the subcellular distribution of thymidine kinase in the rat cerebellum. Brain Res., 1979, 168, 393-397.
89. Absil, J.; Tuilie, M.; Roux, J. M. Electrophoretically distinct forms of uridine kinase in the rat. Tissue distribution and age-dependence. Biochem. J., 1980, 185, 273-276.
90. Suleiman, S. A.; Spector, R. Identification, development, and regional distribution of thymidilate synthase in adult rabbit brain. J. Neurochem., 1982, 38, 392-396.
91. Suleiman, S. A.; Spector, R. Metabolism of deoxyuridine in rabbit brain. J. Neurochem., 1982, 39, 824-830.
92. Spector, T.; Huntoon, S. Characterization, development, and localization of the deoxycytidine phosphorilating systems in mammalian brain. J. Neurochem., 1983, 40, 1481-1486.
93. Cappiello, M.; Mascia, L.; Scolozzi, C.; Giorgelli, F.; Ipata, P. L. In vitro assessment of salvage pathways for pyrimidine bases in rat liver and brain. Biochim. Biophys. Acta, 1998, 1425, 273-281.
94. van Rompay, A. R.; Norda, A.; Lindén, K.; Johansson, M.; Karlsson, A. Phosphorylation of uridine and cytidine nucleoside analogs by two human uridine-cytidine kinases. Mol. Pharmacol., 2001, 59, 1181-1186.
95. van Kuilenburg, A. B.; Stroomer, A. E.; Van Lenthe, H.; Abeling, N. G.; Van Gennip, A. H. New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid? Biochem. J., 2004, 379, 119-124.
96. Löffler, M.; Fairbanks, L. D.; Zameitat, E.; Marinaki, A. M.; Simmonds, H. A. Pyrimidine pathways in health and disease. Trends Mol. Med., 2005, 11, 430-437.
97. Balestri, F.; Barsotti, C.; Lutzemberger, L.; Camici, M.; Ipata, P. L. Key role of uridine kinase and uridine phosphorylase in the homeostatic regulation of purine and pyrimidine salvage in brain. Neurochem. Int., 2007, 51, 517-523.
98. Ipata, P. L.; Barsotti, C.; Tozzi, M. G.; Camici, M.; Balestri, F. Metabolic interplay between intra-and extra-cellular uridine metabolism via an ATP driven uridine-UTP cycle in brain. Int. J. Biochem. Cell Biol., 2010, 42, 932-937.
99. Cansev, M. Uridine and cytidine in the brain: their transport and utilization. Brain Res. Rev., 2006, 52, 389-397.
100. Mascia, L.; Turchi, G.; Bemi, V.; Ipata, P. L. Uracil salvage pathway in PC12 cells. Biochim. Biophys. Acta, 2000, 1524, 45-50.
101. Tozzi, M. G.; Camici, M.; Mascia, L.; Sgarrella, F.; Ipata, P. L. Pentose phosphates in nucleoside interconversion and catabolism. FEBS J., 2006, 273, 1089-1101.
102. Eells, J. T.; Spector, R. Identification, development, and regional distribution of ribonucleoside reductase in adult rat brain. J. Neurochem., 1983, 40, 1008-1012.
103. Spector, R.; Johanson, C. E. The origin of deoxynucleosides in brain: implications for the study of neurogenesis and stem cell therapy. Phar. Res., 2007, 24, 859-867.
104. Bzowska, A.; Kulikowska, E.; Shugar, D. Purine nucleoside phosphorylases: properties, functions, and clinical aspects. Pharmacol. Ther., 2000, 88, 349-425.
105. Nyhan, W. L. Disorders of purine and pyrimidine metabolism. Mol. Genet. Metab., 2005, 86, 25-33.
106. Camici, M.; Micheli, V.; Ipata, P. L.; Tozzi, M. G. Pediatric neurological syndromes and inborn errors of purine metabolism. Neurochem. Int., 2010, 56, 367-378.
107. Phillis, J. W.; Goshgarian, H. G. Adenosine and neurotrauma: therapeutic perspectives. Neurol. Res., 2001, 23, 183-189.
108. Boison, D. Adenosine kinase, epilepsy and stroke: mechanisms and therapies. Trends Pharmacol. Sci., 2006, 27, 652-658.
109. Boison, D. Adenosine augmentation therapies (AATs) for epilepsy: prospect of cell and gene therapies. Epilepsy Res., 2009, 85, 131-141.
110. Marro, P. J.; Mishra, O. P.; Delivoria-Papadopoulos, M. Effect of allopurinol on brain adenosine levels during hypoxia in newborn piglets. Brain Res., 2006, 1073-1074, 444-450.
111. Zetterström, T.; Vernet, L.; Ungerstedt, U.; Tossman, U.; Jonzon, B.; Fredholm, B. B. Purine levels in the intact rat brain, studies with an inplanted perfused hollow fibre. Neurosci. Lett., 1982, 29, 111-115.
112. Hagberg, H.; Andersson, P.; Lacarewicz, J.; Jacobson, I.; Butcher, S.; Sandberg, M. Extracellular adenosine, inosine, hypoxanthine, and xanthine in relation to tissue nucleotides and purines in rat striatum during transient ischemia. J. Neurochem., 1987, 49, 227-231.
113. Pillwein, K.; Chiba, P.; Knoflach, A.; Czermak, B.; Schuchter, K.; Gersdorf, E.; Ausserer, B.; Murr, C.; Goebl, R.; Stockhammer, G. Purine metabolism of human glioblastoma in vivo. Cancer Res., 1990, 50, 1576-1579.
114. Latini, S.; Pedata, F. Adenosine in the central nervous system: release mechanisms and extracellular concentrations. J. Neurochem., 2001, 79, 463-484.
115. Kovács, Z.; Kékesi, K. A.; Bobest, M.; Török, T.; Szilágyi, N.; Szikra, T.; Szepesi, Z.; Nyilas, R.; Dobolyi, A.; Palkovits, M.; Juhász, G. Post mortem degradation of nucleosides in the brain: comparison of human and rat brains for estimation of in vivo concentration of nucleosides. J. Neurosci. Methods., 2005, 148, 88-93.
116. Dobolyi, Á.; Reichart, A.; Szikra, T.; Szilágyi, N.; Kékesi, A. K.; Karancsi, T.; Slegel, P.; Palkovits, M.; Juhász, G. Analysis of purine and pyrimidine bases, nucleosides and deoxynucleosides in brain microsamples (microdialysates and micropunches) and cerebrospinal fluid. Neurochem. Int., 1998, 32, 247-256.
117. Kraupp, M.; Marz, R. Nucleobase and nucleoside transport in mammalian cells. Wien. Klin. Wochenschr., 1995, 107, 677-680.
118. Griffith, G. A.; Jarvis, S. M. Nucleoside and nucleobase transport systems of mammalian cells. Biochim. Biophys. Acta, 1996, 1286, 153-181.
119. Alanko, L.; Porkka-Heiskanen, T.; Soinila, S. Localization of equilibrative nucleoside transporters in the rat brain. J. Chem. Neuroanat., 2006, 31, 162-168.
120. Lee, C. W.; Jarvis, S. M. Nucleoside transport in rat cerebralcortical synaptosomes. Evidence for two types of nucleoside transporters. Biochem. J., 1988, 249, 557-564.
121. Redzic, Z. B.; Malatiali, S. A.; Grujicic, D.; Isakovic, A. J. Expression and functional activity of nucleoside transporters in human choroid plexus. Cerebrospinal Fluid Res., 2010, 7, 2.
122. Johnston, M. E.; Geiger, J. D. Sodium-dependent uptake of nucleosides by dissociated brain cells from the rat. J. Neurochem., 1989, 52, 75-81.
123. Li, J. Y.; Boado, R. J.; Pardridge, W. M. Cloned blood-brain barrier adenosine transporter is identical to the rat concentrative Na+ nucleoside cotransporter CNT2. J. Cereb. Blood Flow Metab., 2001, 21, 929-936.
124. Nagai, K.; Nagasawa, K.; Fujimoto, S. Transport mechanisms for adenosine and uridine in primary-cultured rat cortical neurons and astrocytes. Biochem. Biophys. Res. Commun., 2005, 334, 1343-1350.
125. Redzic, Z. B.; Biringer, J.; Barnes, K.; Baldwin, S. A.; Al-Sarraf, H.; Nicola, P. A.; Young, J. D.; Cass, C. E.; Barrand, M. A.; Hladky, S. B. Polarized distribution of nucleoside transporters in rat brain endothelial and choroid plexus epithelial cells. J. Neurochem., 2005, 94, 1420-1426.
126. Redzic, Z. B.; Isakovic, A. J.; Misirlic, D. S. T.; Popadic, D.; Segal, M. B. Uneven distribution of nucleoside transporters and intracellular enzymatic degradation prevent transport of intact (14C) adenosine across the sheep choroid plexus epithelium as a monolayer in primary culture. Cerebrospinal Fluid Res., 2006, 29, 3-4.
127. Thorn, J. A.; Jarvis, S. M. Adenosine transporters. Gen. Pharmacol., 1996, 27, 613-620.
128. Schaner, M. E.; Gerstin, K. M.; Wang, J.; Giacomini, K. M. Mechanisms of transport of nucleosides and nucleoside analogues in choroid plexus. Adv. Drug Deliver. Rev., 1999, 39, 51-62.
129. Kalaria, R. N.; Harik, S. I. Nucleoside transporter of cerebral microvessels and choroid plexus. J. Neurochem., 1986, 47, 1849-1856.
130. Redzic, Z. B.; Gasic, J. M.; Segal, M. B.; Markovic, I. D.; Isakovic, A. J.; Rakic, M. L.; Thomas, S. A.; Rakic, L. M. The kinetics of hypoxanthine transport across the perfused choroid plexus of the sheep. Brain Res., 2002, 25, 169-175.
131. Spector, R. Hypoxanthine transport and metabolism in the central nervous system. J. Neurochem., 1988, 50, 969-978.
132. Washington, C. B.; Giacomini, K. M. Mechanisms of nucleobase transport in rabbit choroid plexus. Evidence for a Na(+)-dependent nucleobase transporter with broad substrate selectivity. J. Biol. Chem., 1995, 270, 22816-22819.
133. Grundman, M.; Farlow, M.; Peavy, G.; Kim, H. T.; Capparelli, E.; Schultz, A. N.; Salmon, D. P.; Ferris, S. H.; Mobs, R.; Thomas, R. G.; Schafer, K.; Campbell, K.; Hake, A. M.; Schoos, B.; Thal, L. J. A phase I study of AIT-082 in healthy elderly volunteers. J. Mol. Neurosci., 2002, 18, 283-293.
134. Grundman, M.; Capparelli, E.; Kim, H. T.; Morris, J. C.; Farlow, M.; Rubin, E. H.; Heidebrink, J.; Hake, A.; Ho, G.; Schultz, A. N.; Schafer, K.; Houston, W.; Thomas, R.; Thal, L. J. A multicenter, randomized, placebo controlled, multiple-dose, safety and pharmacokinetic study of AIT-082 (Neotrofin) in mild Alzheimer's disease patients. Life Sci., 2003, 73, 539-553.
135. Linker, R. A.; Kieseier, B. C.; Gold, R. Identification and development of new therapeutics for multiple sclerosis. Trends Pharmacol. Sci., 2008, 29, 558-565.
136. Baldwin, S. A.; Yao, S. Y. M.; Hyde, R. J.; Ng, A. M. L.; Foppolo, S.; Barnes, K.; Ritzel, M. W. L.; Cass, C. E.; Young, J. D. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J. Biol. Chem., 2005, 280, 15880-15887.
137. Engel, K.; Zhou, M.; Wang, J. Identification and characterization of a novel monoamine transporter in the human brain. J. Biol. Chem., 2004, 279, 50042-50049.
138. Barnes, K.; Dobrzynski, H.; Foppolo, S.; Beal, P. R.; Ismat, F.; Scullion, E. R.; Sun, L.; Tellez, J.; Ritzel, M. W.; Claycomb, W. C.; Cass, C. E.; Young, J. D.; Billeter-Clark, R.; Boyett, M. R.; Baldwin, S. A. Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ. Res., 2006, 99, 510-519.
139. Hösli, L.; Hösli, E. Autoradiographic studies on the uptake of adenosine and on binding of adenosine analogues in neurons and astrocytes of cultured rat cerebellum and spinal cord. Neuroscience, 1988, 24, 611-628.
140. Daré, E.; Schulte, G.; Karovic, O.; Hammarberg, C.; Fredholm, B. B. Modulation of glial cell functions by adenosine receptors. Physiol. Behav., 2007, 92, 15-20.
141. Cornfield, L. J.; Hu, S.; Hurt, S. D.; Sills, M. A. [3H]2-phenylaminoadenosine ([3H]CV 1808) labels a novel adenosine receptor in rat brain. J. Pharmacol. Exp. Ther., 1992, 263, 552-561.
142. 2A receptors. J. Pharmacol. Exp. Ther., 1995, 272, 511-518.
143. Fredholm, B. B.; Ijzerman, A. P.; Jacobson, K. A.; Klotz, K. N.; Linden, J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol. Rev., 2001, 53, 527-552.
144. Schulte, G.; Fredholm, B. B. Signalling from adenosine receptors to mitogen-activated protein kinases. Cell Signal., 2003, 15, 813-827.
145. 2A receptor blockade. Purinergic Signal., 2005, 1, 111-134.
146. 2A signaling. Prog. Neurobiol., 2007, 83, 263-276.
147. 3 adenosine receptor: an enigmatic player in cell biology. Pharmacol. Ther., 2008, 117, 123-140.
148. Abbracchio, M. P.; Burnstock, G.; Verkhratsky, A.; Zimmermann, H. Purinergic signalling in the nervous system: an overview. Trends Neurosci., 2009, 32, 19-29.
149. Kimura-Takeuchi, M.; Inoue, S. Lateral preoptic lesions void slowwave sleep enhanced by uridine but not by muramyl dipeptide in rats. Neurosci. Lett., 1993, 157, 17-20.
150. Inoue, S.; Honda, K.; Komoda, Y. Sleep as neuronal detoxification and restitution. Behav. Brain Res., 1995, 69, 91-96.
151. 2+ ion fluxes in rat brain homogenates. Neuroreport, 1999, 10, 1577-1582.
152. Kovács, I.; Lasztóczi, B.; Szárics, É.; Héja, L.; Sági, G.; Kardos, J. Characterisation of an uridine-specific binding site in rat cerebrocortical homogenates. Neurochem. Int., 2003, 43, 101-112.
153. Traversa, U.; Bombi, G.; Di Iorio, P.; Ciccarelli, R.; Werstiuk, E. S.; Rathbone, M. P. Specific [(3)H]-guanosine binding sites in rat brain membranes. Br. J. Pharmacol., 2002, 135, 969-976.
154. Traversa, U.; Bombi, G.; Camaioni, E.; Macchiarulo, A.; Costantino, G.; Palmieri, C.; Caciagli, F.; Pellicciari, R. Rat brain guanosine binding site. Biological studies and pseudo-receptor construction. Bioorg. Med. Chem., 2003, 11, 5417-5425.
155. Di Iorio, P.; Ballerini, P.; Traversa, U.; Nicoletti, F.; D'Alimonte, I.; Kleywegt, S.; Werstiuk, E. S.; Rathbone, M. P.; Caciagli, F.; Ciccarelli, R. The antiapoptotic effect of guanosine is mediated by the activation of the PI 3-kinase/AKT/PKB pathway in cultured rat astrocytes. Glia, 2004, 46, 356-368.
156. Bender, E.; Buist, A.; Jurzak, M.; Langlois, X.; Baggerman, G.; Verhasselt, P.; Ercken, M.; Guo, H. Q.; Wintmolders, C.; van den Wyngaert, I.; van Oers, I.; Schoofs, L.; Luyten, W. Characterization of an orphan G protein-coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule. Proc. Natl. Acad. Sci. USA, 2002, 99, 8573-8578.
157. Yoshimi, Y.; Watanabe, S.; Shinomiya, T.; Makino, A.; Toyoda, M.; Ikekita, M. Nucleobase adenine as a trophic factor acting on Purkinje cells. Brain Res., 2003, 991, 113-122.
158. Watanabe, S.; Ikekita, M.; Nakata, H. Identification of specific (3H)adenine-binding sites in rat brain membranes. J. Biochem., (Tokyo) 2005, 137, 323-329.
159. Gorzalka, S.; Vittori, S.; Volpini, R.; Cristalli, G.; von Kugelgen, I.; Muller, C. E. Evidence for the functional expression and pharmacological characterization of adenine receptors in native cells and tissues. Mol. Pharmacol., 2005, 67; 955-964.
160. Von Kügelgen, I.; Schiedel, A. C.; Hoffmann, K.; Alsdorf, B. B.; Abdelrahman, A.; Müller, C. E. Cloning and functional expression of a novel Gi protein-coupled receptor for adenine from mouse brain. Mol. Pharmacol., 2008, 73, 469-477.
161. Blum, D.; Hourez, R.; Galas, M. C.; Popoli, P.; Schiffmann, S. N. Adenosine receptors and Huntington's disease: implications for pathogenesis and therapeutics. Lancet Neurol., 2003, 2, 366-374.
162. Chou, S. Y.; Lee, Y. C.; Chen, H. M.; Chiang, M. C.; Lai, H. L.; Chang, H. H.; Wu, Y. C.; Sun, C. N.; Chien, C. L.; Lin, Y. S.; Wang, S. C.; Tung, Y. Y.; Chang, C.; Chern, Y. CGS21680 attenuates symptoms of Huntington's disease in a transgenic mouse model. J. Neurochem., 2005, 93, 310-320.
163. 2A receptors in Huntington's disease. Prog. Neurobiol., 2007, 81, 331-348.
164. 2A receptor blockade of beta-amyloid neurotoxicity. Br. J. Pharmacol., 2003, 138, 1207-1209.
165. 2 adenosine receptor antagonists on the induction and reversal of long-term potentiation in guinea pig hippocampal slices of CA1 neurons. Cell. Mol. Neurobiol., 2000, 20, 331-350.
166. 2A receptors and brain injury: Broad spectrum of neuroprotection, multifaceted actions and "fine tuning" modulation. Prog. Neurobiol., 2007, 83, 310-331.
167. 2A receptors in inflammation and injury: lessons learned from transgenic animals. J. Leukoc. Biol., 2008, 83, 447-455.
168. Hack, S. P.; Christie, M. J. Adaptations in adenosine signaling in drug dependence: therapeutic implications. Crit. Rev. Neurobiol., 2003, 15, 235-374.
169. 2A) receptor as an attractive target for Parkinson's disease treatment. Drug. News Perspect, 2003, 16, 597-604.
170. 2A receptors in Parkinson's disease. Trends Neurosci., 2006, 29, 647-654.
171. 2A receptors for Parkinson's disease. Neurotherapeutics, 2009, 6, 141-151.
172. 2A antagonists, and Parkinson's disease. Parkinsonism Relat. Disord., 2009, 15, 406-413.
173. 2A adenosine receptor overexpression and functionality, as well as TNF-alpha levels, correlate with motor symptoms in Parkinson's disease. FASEB J., 2010, 24, 587-598.
174. 2B receptor from human brain. Biochem. Biophys. Res. Commun., 1992, 187, 86-93.
175. Atkinson, M. R.; Townsend-Nicholson, A.; Nicholl, J. K.; Sutherland, G. R.; Schofield, P. R. Cloning, characterisation and chromosomal assignment of the human adenosine A3 receptor (ADORA3) gene. Neurosci. Res., 1997, 29, 73-79.
176. Ralevic, V.; Burnstock, G. Receptors for purines and pyrimidines. Pharmacol. Rev., 1998, 50, 413-492.
177. Jacobson, K. A. Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol. Sci., 1998, 19, 184-191.
178. Sebastiao, A. M.; Ribeiro, J. A. Fine-tuning neuromodulation by adenosine. Trends Pharmacol. Sci., 2000, 21, 341-346.
179. Strecker, R. E.; Morairty, S.; Thakkar, M. M.; Porkka-Heiskanen, T.; Basheer, R.; Dauphin, L. J.; Rainnie, D. G.; Portas, C. M.; Greene, R. W.; McCarley, R. W. Adenosinergic modulation of basal forebrain and preoptic/anterior hypothalamic neuronal activity in the control of behavioral state. Behav. Brain Res., 2000, 115, 183-204.
180. Cunha, R. A. Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem. Int., 2001, 38, 107-125.
181. Wardas, J. Neuroprotective role of adenosine in the CNS. Pol. J. Pharmacol., 2002, 54, 313-326.
182. Haskó, G.; Pacher, P.; Vizi, E. S.; Illes, P. Adenosine receptor signaling in the brain immune system. Trends Pharmacol. Sci., 2005, 26, 511-516.
183. Haskó, G.; Cronstein, B. N. Adenosine: an endogenous regulator of innate immunity. Trends Immunol., 2004, 25, 33-39.
184. Lara, D. R.; Dall'Igna, O. P.; Ghisolfi, E. S.; Brunstein, M. G. Involvement of adenosine in the neurobiology of schizophrenia and its therapeutic implications. Prog. Neuro-Psychop., 2006, 30, 617-629.
185. Xie, X.; Ramkumar, V.; Toth, L. A. Adenosine and dopamine receptor interactions in striatum and caffeine-induced behavioral activation. Comp. Med., 2007, 57, 538-545.
186. Landolt, H. P. Sleep homeostasis: A role for adenosine in humans? Biochem. Pharmacol., 2008, 75, 2070-2079.
187. Dobolyi, A.; Szikra, T.; Kékesi, A. K.; Kovács, Z.; Juhász, G. Uridine is released by depolarization and inhibits unit activity in the rat hippocampus. Neuroreport, 1999, 10, 3049-3053.
188. Chen, P.; Goldberg, D. E.; Kolb, B.; Lanser, M.; Benowitz, L. I. Inosine induces axonal rewiring and improves behavioral outcome after stroke. Proc. Natl. Acad. Sci. USA, 2002, 99, 9031-9036.
189. Slézia, A.; Kékesi, A. K.; Szikra, T.; Papp, A. M.; Nagy, K.; Szente, M.; Maglóczky, Zs.; Freund, T. F.; Juhász, G. Uridine release during aminopyridine-induced epilepsy. Neurobiol. Dis., 2004, 16, 490-499.
190. Shen, H.; Chen, G. J.; Harvey, B. K.; Bickford, P. C.; Wang, Y. Inosine reduces ischemic brain injury in rats. Stroke, 2005, 36, 654-659.
191. Zhao, Q.; Marolewski, A.; Rusche, J. R.; Holmes, G. L. Effects of uridine in models of epileptogenesis and seizures. Epilepsy Res., 2006, 70, 73-82.
192. Haskó, G.; Kuhel, D. G.; Németh, Z. H.; Mabley, J. G.; Stachlewitz, R. F.; Virág, L.; Lohinai, Zs.; Southan, G. J.; Salzman, A. L.; Szabó, C. Inosine inhibits inflammatory cytokine production by a posttranscriptional mechanism and protects against endotoxininduced shock. J. Immunol., 2000, 164, 1013-1019.
193. Löeffler, D. A.; Lewitt, P. A.; Juneau, P. L.; Camp, D. M.; Demaggio, A. J.; Milbury, P.; Matson, W. R.; Rathbone, M. P. Altered guanosine and guanine concentrations in rabbit striatum following increased dopamine turnover. Brain Res. Bull., 1998, 45, 297-299.
194. Cansev, M.; Wurtman, R. J.; Sakamoto, T.; Ulus, I. H. Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses. Alzheimers Dement., 2008, 4, 153-168.
195. Wurtman, R. J.; Cansev, M.; Sakamoto, T.; Ulus, I. H. Use of phosphatide precursors to promote synaptogenesis. Annu. Rev. Nutr., 2009, 29, 59-87.
196. Wurtman, R. J.; Cansev, M.; Ulus, I. H. Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides. J. Nutr. Health Aging., 2009, 13, 189-197.
197. Carlezon, W. A.; Pliakas, A. M.; Parow, A. M.; Detke, M. J.; Cohen, B. M.; Renshaw, P. F. Antidepressant-like effects of cytidine in the forced swim test in rats. Biol. Psychiat., 2002, 51, 882-889.
198. Yamamoto, S.; Wang, M. F.; Adjei, A. A.; Ameho, C. K. Role of nucleosides and nucleotides in the immune system, gut reparation after injury, and brain function. Nutrition, 1997, 13, 372-374.
199. Chen, T. H.; Wang, M. F.; Liang, Y. F.; Komatsu, T.; Chan, Y. C.; Chung, S. Y.; Yamamoto, S. A nucleoside-nucleotide mixture may reduce memory deterioration in old senescence-accelerated mice. J. Nutr., 2000, 130, 3085-3089.
200. Balestri, F.; Giannecchini, M.; Sgarrella, F.; Carta, M. C.; Tozzi, M. G.; Camici, M. Purine and pyrimidine nucleosides preserve human astrocytoma cell adenylate energy charge under ischemic conditions. Neurochem. Int., 2007, 50, 517-523.
201. Christjanson, L. J.; Middlemiss, P. J.; Rathbone, M. P. Stimulation of astrocyte proliferation by purine and pyrimidine nucleotides and nucleosides. Glia, 1993, 7, 176-182.
202. Kong, W.; Wang, J. Hypoxanthine transport in human glioblastoma cells and effect on cell susceptibility to methotrexate. Pharm. Res., 2003, 20, 1804-1811.
203. Dessi, F.; Pollard, H.; Moreau, J.; Ben-Ari, Y.; Charriaut-Marlangue, C. Cytosine arabinoside induces apoptosis in cerebellar neurons in culture. J. Neurochem., 1995, 64, 1980-1987.
204. Kleihues, P.; Kobayashi, K.; Hossmann, K. A. Purine nucleotide metabolism in the cat brain after one hour of complete ischemia. J. Neurochem., 1974, 23, 417-425.
205. Traut, T. W. Physiological concentrations of purines and pyrimidines. Mol. Cell. Biochem., 1994, 140, 1-22.
206. Zimmermann, H. Signalling via ATP in the nervous system. Trends Neurosci., 1994, 17, 420-426.
207. Berne, R. M.; Rubio, R.; Curnish, R. R. Release of adenosine from ischemic brain: effect on cerebral vascular resistance and incorporation into cerebral adenine nucleotides. Circ. Res., 1974, 35, 262-271.
208. Dux, E.; Fastbom, J.; Ungerstedt, U.; Rudolphi, K.; Fredholm, B. B. Protective effect of adenosine and a novel xanthine derivative propentofylline on the cell damage after bilateral carotid occlusion in the gerbil hippocampus. Brain Res., 1990, 516, 248-256.
209. Matsumoto, K.; Graf, R.; Rosner, G.; Shimada, N.; Heiss, W. D. Flow thresholds for extracellular purine catabolite elevation in cat focal ischemia. Brain Res., 1992, 579, 309-314.
210. Nordström, C. H.; Rehncrona, S.; Siesjö, B. K.; Westerberg, E. Adenosine in rat cerebral cortex: its determination, normal values, and correlation to AMP and cyclic AMP during shortlasting ischemia. Acta Physiol. Scand, 1977, 101, 63-71.
211. Wojcik, W. J.; Neff, N. H. Adenosine measurement by a rapid HPLC fluorometric method: induced changes of adenosine content in regions of rat brain. J. Neurochem., 1982, 39, 280-282.
212. Harkness, R. A.; Lund, R. J. Cerebrospinal fluid concentrations of hypoxanthine, xanthine, uridine and inosine: high concentrations of the ATP metabolite, hypoxanthine, after hypoxia. J. Clin. Pathol., 1983, 36, 1-8.
213. Eells, J. T.; Spector, R. Purine and pyrimidine base and nucleoside concentrations in human cerebrospinal fluid and plasma. Neurochem. Res., 1983, 8, 1451-1457.
214. Phillis, J. W.; Walter, G. A.; O'Regan, M. H.; Stair, R. E. Increases in cerebral cortical perfusate adenosine and inosine concentrations during hypoxia and ischemia. J. Cereb. Blood Flow Metab., 1987, 7, 679-686.
215. van Wylen, D. G.; Park, T. S.; Rubio, R.; Berne, R. M. Increases in cerebral interstitial fluid adenosine concentration during hypoxia, local potassium infusion, and ischemia. J. Cereb. Blood Flow Metab., 1986, 6, 522-528.
216. Ballarin, M.; Herrera-Marschitz, M.; Casas, M.; Ungerstedt, U. Striatal adenosine levels measured 'in vivo' by microdialysis in rats with unilateral dopamine denervation. Neurosci. Lett., 1987, 83, 338-344.
217. Hillered, L.; Hallström, A.; Segersvärd, S.; Persson, L.; Ungerstedt, U. Dynamics of extracellular metabolites in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis. J. Cereb. Blood Flow Metab., 1989, 9, 607-616.
218. Sciotti, V. M.; Park, T. S.; Berne, R. M.; Van Wylen, D. G. L. Changes in extracellular adenosine during chemical or electrical brain stimulation. Brain Res., 1993, 613, 16-20.
219. Carswell, H. V.; Graham, D. I.; Stone, T. W. Kainate-evoked release of adenosine from the hippocampus of the anaesthetised rat: possible involvement of free radicals. J. Neurochem., 1997, 68, 240-247.
220. Dobolyi, Á.; Reichart, A.; Szikra, T.; Nyitrai, G.; Kékesi, K. A.; Juhász, G. Sustained depolarization induces changes in the extracellular concentrations of purine and pyrimidine nucleosides in the rat thalamus. Neurochem. Int., 2000, 37, 71-79.
221. Dale, N.; Pearson, T.; Frenguelli, B. G. Direct measurement of adenosine release during hypoxia in the CA1 region of the rat hippocampal slice. J. Physiol., 2000, 526, 143-155.
222. Wall, M. J.; Atterbury, A.; Dale, N. Control of basal extracellular adenosine concentration in rat cerebellum. J. Physiol., 2007, 582, 137-151.
223. Chen, Y.; Graham, D. I.; Stone, T. W. Release of endogenous adenosine and its metabolites by the activation of NMDA receptors in the rat hippocampus in vivo. Br. J. Pharmacol., 1992, 106, 632-638.
224. Park, T. S.; Van Wylen, D. G.; Rubio, R.; Berne, R. M. Increased brain interstitial fluid adenosine concentration during hypoxia in newborn piglet. J. Cereb. Blood Flow Metab., 1987, 7, 178-183.
225. Nagata, H.; Mimori, Y.; Nakamura, S.; Kameyama, M. Regional and subcellular distribution in mammalian brain of the enzymes producing adenosine. J. Neurochem., 1984, 42, 1001-1007.
226. Geiger, J. D.; Nagy, J. I. Distribution of adenosine deaminase activity in rat brain and spinal cord. J. Neurosci., 1986, 6, 2707-2714.
227. Yamamoto, T.; Geiger, J. D.; Daddona, P. E.; Nagy, J. I. Subcellular, regional and immunhistochemical localisation of adenosine deaminase in various species. Brain Res. Bull., 1987, 19, 473-484.
228. van der Weyden, M. B.; Kelley, W. N. Human adenosine deaminase. Distribution and properties. J. Biol. Chem., 1976, 251, 5448-5456.
229. Norstrand, I. F.; Siverls, V. C.; Libbin, R. M. Regional distribution of adenosine deaminase in the human neuraxis. Enzyme, 1984, 32, 20-25.
230. 3H]nitrobenzylthioinosine in rat brain: an autoradiographic and membrane binding study. Brain Res. Bull., 1984, 13, 657-666.
231. Norstrand, I.; Libbin, R.; Druck, P.; Enker, S. The histochemical demonstration of guanase: observations in the human central nervous system. Acta Histochem., 1979, 64, 187-193.
232. Berger, S. J.; Carter, J. G.; Lowry, O. H. Distribution of guanine deaminase in mouse brain. J. Neurochem., 1985, 44, 1736-1740.
233. Norstrand, I. F.; Glantz, M. D. Topographical distribution of purine nucleoside phosphorylase in the human neuraxis. Enzyme, 1980, 25, 118-122.
234. Trolin, C. G.; Lofberg, C.; Trolin, G.; Oreland, L. Brain ATP:Lmethionine S-adenosyltransferase (MAT), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH): regional distribution and age-related changes. Eur. Neuropsychopharmacol., 1994, 4, 469-477.
235. Thörner, G.; Lange, H.; Hopf, A. Morphometrical-statistical structure analysis of human striatum, pallidus and subthalamic nucleus. II. Globus pallidus. J. Hirnforsch., 1975, 16, 401-413.
236. Diamond, M. C.; Scheibel, A. B.; Murphy, G. M. Jr.; Harvey, T. On the brain of a scientist: Albert Einstein. Exp. Neurol., 1985, 88, 198-204.
237. Pakkenberg, B.; Gundersen, H. J. Total number of neurons and glial cells in human brain nuclei estimated by the dissector and the fractionator. J. Microsc., 1988, 15, 1-20.
238. Öngür, D.; Drevets, W. C.; Price, J. L. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc. Natl. Acad. Sci. USA, 1998, 95, 13290-13295.
239. Leuba, G.; Garey, L. J. Comparison of neuronal and glial numerical density in primary and secondary visual cortex of man. Exp. Brain Res., 1989, 77, 31-38.
240. Bowley, M. P.; Drevets, W. C.; Öngür, D.; Price, J. L. Low glial numbers in the amygdala in major depressive disorder. Biol. Psychiatry., 2002, 52, 404-412.
241. Ceballos, G.; Tuttle, J. B.; Rubio, R. Differential distribution of purine metabolizing enzymes between glia and neurons. J. Neurochem., 1994, 62, 1144-1153.
242. Zoref-Shani, E.; Bromberg, Y.; Lilling, G.; Gozes, I.; Brosh, S.; Sidi, Y.; Sperling, O. Developmental changes in purine nucleotide metabolism in cultured rat astroglia. Int. J. Devl. Neurosc., 1995, 13, 887-896.
243. Ghandour, M. S.; Vincendon, G.; Gombos, G. Astrocyte and oligodendrocyte distribution in adult rat cerebellum: an immunohistological study. J. Neurocytol., 1980, 9, 637-646.
244. Kovács, Z.; Dobolyi, A.; Szikra, T.; Palkovits, M.; Juhász, G. Uneven regional distribution of nucleotide metabolism in human brain. Neurobiology, (Bp) 1998, 6, 315-321.
245. Parkinson, F. E.; Sinclair, C. J. D.; Othman, T.; Haughey, N. J.; Geiger, J. D. Differences between rat primary cortical neurons and astrocytes in purine release evoked by ischemic conditions. Neuropharmacology, 2002, 43, 836-846.
246. Anderson, C. M.; Xiong, W.; Geiger, J. D.; Young, J. D.; Cass, C. E.; Baldwin, S. A.; Parkinson, F. E. Distribution of equilibrative, nitrobenzylthioinosine-sensitive nucleoside transporters (ENT1) in brain. J. Neurochem., 1999, 73, 867-873.
247. Nagai, K.; Nagasawa, K.; Matsugana, R.; Yamaji, M.; Fujimoto, S. Novel Na+-independent and adenine-specific transport system for adenine in primary cultured rat cortical neurons. Neurosci. Lett., 2006, 407, 244-248.
248. Jarvis, M. F.; Williams, M. Differences in adenosine A-1 and A-2 receptor density revealed by autoradiography in methylxanthinesensitive and insensitive mice. Pharmacol. Biochem. Behav., 1988, 30, 707-714.
249. 1 adenosine receptor from rat brain. Mol. Pharmacol., 1991, 40, 1-7.
250. 1-adenosine receptor that is widely expressed in brain and spinal cord. Mol. Endocrinol., 1991, 5, 1037-1048.
251. Dixon, A. K.; Gubitz, A. K.; Sirinathsinghji, D. J.; Richardson, P. J.; Freeman, T. C. Tissue distribution of adenosine receptor mRNAs in the rat. Br. J. Pharmacol., 1996, 118, 1461-1468.
252. 11C)8-dicyclopropylmethyl-1-methyl-3-propylxanthine. Nucl. Med. Biol., 2004, 31, 975-981.
253. Rudolphi, K. A.; Schubert, P.; Parkinson, F. E.; Fredholm, B. B. Adenosine and brain ischemia. Cerebrovasc. Brain Metab. Rev., 1992, 4, 346-369.
254. Pedata, F.; Pazzagli, M.; Tilli, S.; Pepeu, G. Regional differences in the electrically stimulated release of endogenous and radioactive adenosine and purine derivatives from rat brain slices. Naunyn-Schmiedeberg's Arch. Pharmacol., 1990, 342, 447-453.
255. 1 adenosine receptor and 5'-nucleotidase in pig brain cortex subcellular fractions. Neurochem. Res., 1992, 17, 129-139.
256. 2A receptors in the rat central nervous system. J. Comp. Neurol., 1998, 401, 163-186.
257. 3 adenosine receptor. Proc. Natl. Acad. Sci. USA, 1993, 90, 10365-10369.
258. Brundege, J. M.; Williams, J. T. Increase in adenosine sensitivity in the nucleus accumbens following chronic morphine treatment. J. Neurophysiol., 2002, 87, 1369-1375.
259. Sawynok, J.; Liu, X. J. Adenosine in the spinal cord and periphery: release and regulation of pain. Prog. Neurobiol., 2003, 69, 313-340.
260. Frostholm, A.; Rotter, A. Autoradiographic localization of receptors in the cochlear nucleus of the mouse. Brain Res. Bull., 1986, 16, 189-203.
261. Guroff, G.; Rhoads, C. A. Uridine phosphorylase from rat brain: characteristics and developmental course. J. Neurochem., 1969, 16, 1543-1549.
262. Geiger, J. D., Nagy, J. I. Ontogenesis of adenosine deaminase activity in rat brain. J. Neurochem., 1987, 48, 147-153.
263. Jin, Z. L.; Lee, T. F.; Zhou, S. J.; Wang, L. C. Age-dependent change in the inhibitory effect of an adenosine agonist on hippocampal acetylcholine release in rats. Brain Res. Bull., 1993, 30, 149-152.
264. 1-adenosine receptors in rat hippocampal slices. Int. J. Dev. Neurosci., 1997, 15, 739-747.
265. Cunha, R. A.; Almeida, T.; Ribeiro, J. A. Parallel modification of adenosine extracellular metabolism and modulatory action in the hippocampus of aged rats. J. Neurochem., 2001, 76, 372-382.
266. Pazzagli, M.; Corsi, C.; Fratti, S.; Pedata, F.; Pepeu, G. Regulation of extracellular adenosine levels in the striatum of aging rats. Brain Res., 1995, 684, 103-106.
267. Allsop, J.; Watts, R. W. E. Activities of amido phosphoribosyltransferase and purine phosphoribosyltransferases and the phosphoribosylpyrophosphate content of rat central nervous system at different stages of development. J. Neurol. Sci., 1980, 46, 221-222.
268. Wegelin, I.; Pane, G.; Clo, C. Studies of pyrimidine metabolism during chick development: two enzymes involved in UMP breakdown. Ital. J. Biochem., 1990, 39, 361-367.
269. Snyder, D. S.; Zimmerman, T. R. Jr.; Farooq, M.; Norton, W. T.; Cammer, W. Carbonic anhydrase, 5'-nucleotidase, and 2',3'-cyclic nucleotide-3'-phosphodiesterase activities in oligodendrocytes, astrocytes, and neurons isolated from the brains of developing rats. J. Neurochem., 1983, 40, 120-127.
270. 2A receptors in rat brain: comparison with dopamine receptors. Neuroscience, 1997, 80, 1187-1207.
271. 2a adenosine receptor binding in aged striatum, hippocampus and cortex of the rat. Neuroreport, 1995, 6, 1583-1588.
272. 1 receptors in dementia: evidence for lack of specificity. Neurosci. Lett., 1998, 244, 1-4.
273. 1 receptor and uptake site binding in the mouse brain: an autoradiographic study. J. Neurosci. Res., 2000, 60, 257-265.
274. 1 adenosine receptors: a [18F]CPFPX PET study in humans. Neurobiol. Aging, 2007, 28, 1914-1924.
275. 2A receptors in the limbic cortex, but not striatum, of aged rats. J. Neurochem., 1999, 73, 1733-1738.
276. Simic, G.; Bexheti, S.; Kelovic, Z.; Kos, M.; Grbic, K.; Hof, P. R.; Kostovic, I. Hemispheric asymmetry, modular variability and agerelated changes in the human entorhinal cortex. Neuroscience, 2005, 130, 911-925.
277. Kulkarni, J. S.; Wakade, A. R. Quantitative analysis of similarities and differences in neurotoxicities caused by adenosine and 2'-deoxyadenosine in sympathetic neurons. J. Neurochem., 1996, 67, 778-786.
278. Ceruti, S.; Barbieri, D.; Veronese, E.; Cattabeni, F.; Cossarizza, A.; Giammarioli, A. M.; Malorni, W.; Franceschi, C.; Abbracchio, M. P. Different pathways of apoptosis revealed by 2-chloro-adenosine and deoxy-D-ribose in mammalian astroglial cells. J. Neurosci. Res., 1997, 15, 372-383.
279. Rathbone, M. P.; Middlemiss, P. J.; Gysbers, J. W.; Andrew, C.; Herman, M. A.; Reed, J. K.; Ciccarelli, R.; Di Iorio, P.; Caciagli, F. Trophic effects of purines in neurons and glial cells. Prog. Neurobiol., 1999, 59, 663-690.
280. Chen, T. H.; Huang, H. P.; Matsumoto, Y.; Wu, S. H.; Wang, M. F.; Chung, S. Y.; Uezu, K.; Moriyama, T.; Uezu, E.; Korin, T.; Sato, S.; Yamamoto, S. Effects of dietary nucleoside-nucleotide mixture on memory in aged and young memory deficient mice. Life Sci., 1996, 59, 325-330.
281. De Paula, C. G.; Bruno, A. N.; Vuaden, F. C.; Sarkis, J. J.; Bonan, C. D. Ontogenetic profile of ectonucleotidase activities from brain synaptosomes of pilocarpine-treated rats. Int. J. Dev. Neurosci., 2005, 23, 703-709.
282. Collado, P.; Guillamón, A.; Valencia, A.; Segovia, S. Sexual dimorphism in the bed nucleus of the accessory olfactory tract in the rat. Brain Res. Dev. Brain Res., 1990, 56, 263-268.
283. 1 receptor agonist or an NMDA receptor antagonist. Alcohol Clin. Exp. Res., 2008, 32, 1260-1270.
284. Faught, E. Epidemiology and drug treatment of epilepsy in elderly people. Drugs Aging, 1999, 15, 255-269.
285. Moller, H. J.; Barbera, J.; Kayumov, L.; Shapiro, C. M. Psychiatric aspects of late-life insomnia. Sleep Med. Rev., 2004, 8, 31-45.
286. Ancoli-Israel, S.; Cooke, J. R. Prevalence and comorbidity of insomnia and effect on functioning in elderly populations. J. Am. Geriatr. Soc., 2005, 53, 264-271.
287. Fiske, A.; Wetherell, J. L.; Gatz, M. Depression in older adults. Annu. Rev. Clin. Psychol., 2009, 5, 363-389.
288. Cakatay, U.; Aydin, S.; Yanar, K.; Uzun, H. Gender-dependent variations in systemic biomarkers of oxidative protein, DNA, and lipid damage in aged rats. Aging Male, 2010, 13, 51-58.
289. Von Arnim, C. A.; Etrich, S. M.; Timmler, M.; Riepe, M. W. Gender-dependent hypoxic tolerance mediated via gender-specific mechanisms. J. Neurosci. Res., 2002, 68, 84-88.
290. Markham, J. A.; McKian, K. P.; Stroup, T. S.; Juraska, J. M. Sexually dimorphic aging of dendritic morphology in CA1 of hippocampus. Hippocampus, 2005, 15, 97-103.