Cerebrolysin lowers kynurenic acid formation - An in vitro study

European Neuropsychopharmacology

Volumn 19, Issue 3, 2009, Pages 161-168

  Baran, Halina ^a,b   Kepplinger, Berthold ^b,c,d  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b Karl Landsteiner Research Institute for Pain Treatment and Neurorehabilitation   (Austria)

^c Neuropsychiatric Hospital Mauer   (Austria)

^d General Hospital Amstetten   (Austria)

Author keywords

Cerebrolysin; Cholinergic receptor; Dementia; Kynurenic acid; Kynurenine aminotransferases; NMDA receptor

Indexed keywords

CEREBROLYSIN; CHOLINERGIC RECEPTOR; KYNURENIC ACID; KYNURENINE; KYNURENINE AMINOTRANSFERASE; KYNURENINE AMINOTRANSFERASE 1; KYNURENINE AMINOTRANSFERASE 2; KYNURENINE AMINOTRANSFERASE 3; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL TISSUE; ARTICLE; BRAIN HOMOGENATE; BRAIN INJURY; CHOLINERGIC TRANSMISSION; CONTROLLED STUDY; DEMENTIA; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME SYNTHESIS; HUMAN; HUMAN TISSUE; LIVER HOMOGENATE; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; RADIOENZYMATIC ASSAY; RAT;

ADULT; AMINO ACIDS; ANALYSIS OF VARIANCE; ANIMALS; BRAIN; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTROCHEMISTRY; GLUTAMIC ACID; HUMANS; KYNURENIC ACID; LIVER; MALE; NEUROPROTECTIVE AGENTS; POSTMORTEM CHANGES; RATS; RATS, SPRAGUE-DAWLEY; TIME FACTORS; TRANSAMINASES; TRYPTOPHAN;

EID: 58949086633     PISSN: 0924977X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.euroneuro.2008.09.003     Document Type: Article

References (60)

1. Álvarez X.A., Lombardi V.R.M., Corzo L., Pérez P., Pichel V., Laredo M., Hernández A., Freixeiro F., Sampedro C., Lorenzo R., Alcaraz M., Windisch M., and Cacabelos R. Oral Cerebrolysin enhances brain alpha activity and improves cognitive performance in elderly control subjects. J. Neural Transm. 59 (2000) 315-328
2. Álvarez X.A., Lombardi V.R.M., Fernández-Novoa L., García M., Sampedro C., Cagiao A., Cacabelos R., and Windisch M. Cerebrolysin reduces microglia activation in vivo and in vitro: a potential mechanism of neuroprotection. J. Neural Transm. 59 (2000) 281-292
3. Álvarez X.A., Sampedro C., Pérez P., Laredo M., Couceiro V., Hernández A., Figueroa J., Valera M., Arias D., Corzo L., Zas R., Lombardi V., Fernández-Novoa L., Pichel V., Cacabelos R., Windisch M., Aleixandre M., and Moessler H. Positive effects of Cerebrolysin on electroencephalogram slowing, cognition and clinical outcome in patients with postacute traumatic brain injury: an exploratory study. Int. Clin. Psychopharmacol. 18 (2003) 271-278
4. Álvarez X.A., Cacabelos R., Ladero M., Couceiro V., Sampedro C., Varela M., Corzo L., Fernandez-Novoa L., Vargas M., Aleixandre M., Linares C., Granizo E., Muresanu D., and Moessler H. A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease. Eur. J. Neurol. 13 1 (2006) 43-54
5. Baran H., and Kepplinger B. Cerebrolysin reduces the human brain kynurenine aminotransferase I and II activities. 6th Congress of International College of Geriatric Psychoneuropharmacology Hiroshima, Japan, Abs. Proc., P-C-29 (2006)
6. Baran H., and Kepplinger B. Porcine tissues influence kynurenic acid formation. Parkinsonism & Related Disorders. Parkinsonism & Related Disorders vol 12 (2006) Supp 1, ISSN 1353-8020, IV.P13, 36
7. Baran H., Okuno E., Kido R., and Schwarcz R. Purification and characterisation of kynurenine aminotransferase I from human brain. J. Neurochem. 62 (1994) 730-738
8. Baran H., Gramer M., Hönack D., and Löscher W. Systemic administration of kainate induces marked increase of endogenous kynurenic acid in various brain regions and plasma of rats. Eur. J. Pharmacol. 286 (1995) 167-175
9. Baran H., Cairns N., Lubec B., and Lubec G. Increased kynurenic acid levels and decreased brain kynurenine aminotransferase I in patients with DOWN syndrome. Life Sci. 58 21 (1996) 1891-1899
10. Baran H., Amann G., Lubec B., and Lubec G. Kynurenic acid and kynurenine aminotransferase in heart. Pediatr. Res. 41 3 (1997) 404-410
11. Baran H., Jellinger K., and Deecke L. Kynurenine metabolism in Alzheimer's disease. J. Neural Transm. 106 (1999) 165-181
12. Baran H., Hainfellner J.A., Kepplinger B., Mazal P.R., Schmid H., and Budka H. Kynurenic acid metabolism in the brain of HIV-1 infected patients. J. Neural Transm. 107 (2000) 1127-1138
13. Baran H., Kepplinger B., Herrera-Marschitz M., Stolze K., Lubec G., and Nohl H. Increased kynurenic acid in the brain after neonatal asphyxia. Life Sci. 69 (2001) 1249-1256
14. Baran H., Staniek K., Kepplinger B., Stur I., Draxler M., and Nohl H. Kynurenines and the respiratory parameters in rat heart mitochondria. Life Sci. 72 (2003) 1103-1115
15. Birch P.J., Grossman C.J., and Hayesm A.G. Kynurenic acid antagonizes responses to NMDA via an action at the strychnine-insensitive glycine receptor. Eur. J. Pharmacol. 154 (1988) 85-87
16. Chess A.C., Simoni M.K., Alling T.E., and Bucci D.J. Elevations of kynurenic acid produce working memory deficits. Schizophr. Bull. 33 3 (2007) 797-804
17. Crook T.H., Ferris S.H., Alvarez X.A., Laredo M., and Moessler H. Effect of N-PEP-12 on memory among older adults. Int. Clin. Psychopharmacol. 20 (2005) 97-100
18. Du F., Schmidt W., Okuno E., Kido R., Köhler C., and Schwarcz R. Localization of kynurenine aminotransferase immunoreactivity in the rat hippocampus. J. Comp. Neurol. 321 3 (1992) 477-487
19. Foster A.C., Vezzani A., French E.D., and Schwarcz R. Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci. Lett. 48 (1984) 273-278
20. Gramsbergen J.B.P., Schmidt W., Turski W.A., and Schwarcz R. Age-related changes in kynurenic acid production in rat brain. Brain Res. 588 (1992) 1-5
21. Guidetti P., Amori L., Sapko M.T., Okuno E., and Schwarcz R. Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain. J. Neurochem. 102 (2007) 103-111
22. Guidetti P., Hoffman G.E., Melendez-Ferro M., Albuquerque E.X., and Schwarcz R. Astrocytic localization of Kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry. Glia 55 1 (2007) 78-92
23. Guillemin G.J., Kerr S.J., Smythe G.A., Smith D.G., Kapoor V., Armati P.J., Croitoru J., and Brew B.J. Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection. J. Neurochem. 78 4 (2001) 842-853
24. Han Q., Li J., and Li J. pH dependence, substrate specificity and inhibition of human kynurenine aminotransferase I. Euro. J. Biochem. 271 (2004) 4804-4814
25. 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients. J. Neuroimmunol. 40 1 (1992) 71-80
26. Hilmas C., Pereira E.F.R., Alkondon M., Rassoulpour A., Schwarcz R., and Albuquerque E.X. The brain metabolite kynurenic acid inhibits α7 nicotinic receptor activity and increases non-α7 nicotinic receptor expression: physiopathological implications. J. Neurosci. 21 (2001) 7463-7473
27. Hol E.M., Roelofs R.F., Moraal E., Sonnemans M.A., Sluijs J.A., Proper E.A., de Graan P.N., Fischer D.F., and van Leeuwen F.W. Neuronal expression of GFAP in patients with Alzheimer pathology and identification of novel GFAP splice forms. Mol. Psychiatry 8 9 (2003) 786-796
28. Ishikawa T., Okuno E., Tsujimoto M., Nakamura M., and Kido R. Kynrenine-pyruvate aminotransferase in rat kidney and brain. In: Schwarcz R., Young S.N., and Brown R.R. (Eds). Kynurenine and Serotonin Pathways: Progress in Tryptophan Research. Advances in Experimental Medicine and Biology vol. 294 (1989), Plenum Publishing Corporation, New York 567-572 ISBN 0-306-43929-8
29. Kepplinger B., Baran H., Kalina P., Kainz A., and Nohl H. Subcortical sclerotic Encephalopathie (SSEP) is associated with increased kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF), XXIX. Slovenské a Ceské Neurovasculárne Sympósium, Bratislava 19-20 Octóbra 2001 Abstract Book (2001) 76-77
30. 2-microglobulin changes. NeuroSignals 14 3 (2005) 126-135
31. Kido R. Kynurenate forming enzymes in liver, kidney and brain. In: Schwarcz R., Young S.N., and Brown R.R. (Eds). Kynurenine and Serotonin Pathways: Progress in Tryptophan Research. Advances in Experimental Medicine and Biology vol. 294 (1989), Plenum Publishing Corporation, New York 201-205 ISBN 0-306-43929-8
32. Kiss C., Ceresoli-Borroni G., Guidetti P., Zielke C.L., Zielke H.R., and Schwarcz R. Kynurenate production by cultured human astrocytes. J. Neural Transm. 110 1 (2003) 1-14
33. Ladurner G., Kalvach P., and Moessler H. The Cerebrolysin Study Group: neuroprotective treatment with Cerebrolysin in patients with acute stroke: a randomized controlled trial. J. Neural Transm. 112 (2005) 415-428
34. Magnusson K.R. Aging of glutamate receptors: correlation between binding and spatial memory performance in mice. Mech. Ageing Dev. 104 3 (1998) 227-248
35. Masliah E., Armasolo F., Veinbergs I., Mallory M., and Samuel W. Cerebrolysin ameliorates performance deficits, and neuronal damage in apolipoprotein E-deficient mice. Pharmacol. Biochem. Behav. 62 2 (1999) 239-245
36. McMaster O.G., Baran H., Wu H.-Q., Du F., French E., and Schwarcz R. γ-Acetylenic GABA produces axon-sparing neurodegeneration after focal injection into the rat hippocampus. Exp. Neurol. 124 (1993) 184-191
37. Monzón-Mayor M., Álvarez M.I., Arbelo-Galván J.F., Romero-Alemán M.M., Yanes C., Plaza M.-L., Rodríguez J.R., Rodríguez J.J., and Toledano A. Long-term evolution of local, proximal and remote astrocyte responses after diverse nucleus basalis lesioning (an experimental Alzheimer model): GFAP immunocytochemical study. Brain Res. 865 2 (2000) 245-258
38. Muresanu D.F., Alvarez X.A., Moessler H., Buia M., Stan A., Pintea D., Moldovan F., and Popescu B.O. A pilot study to evaluate the effect of Cerebrolysin on cognition and qEEG in vascular dementia: cognitive impairment correlates with qEEG acceleration. J. Neurol. Sci. 267 1 (2008) 112-119
39. Okuno E., Du F., Ishikawa T., Tsujimoto M., Nakamura M., Schwarcz R., and Kido. Purification and characterisation of kynurenine-pyruvate aminotransferase from rat kidney and brain. Brain Res. 534 (1990) 37-44
40. Okuno E., Nakamura M., and Schwarcz R. Two kynurenine aminotransferases in human brain. Brain Res. 542 (1991) 307-312
41. Ren J., Sietsma D., Qiu S., Moessler H., and Finklestein S.P. Cerebrolysin enhances functional recovery following focal cerebral infarction in rats. Restor. Neurol. Neurosci. 25 1 (2007) 25-31
42. Richter A., Löscher W., Baran H., and Gramer M. Increased levels of kynurenic acid in brains of genetically dystonic hamster. Dev. Brain Res. 92 (1996) 111-116
43. Riley C., Hutter Paier B., Windisch M., Doppler E., Moessler H., and Wrowski R. A peptide preparation protects cells in organotypic brain slices against cell death after glutamate intoxication. J. Neural Transm. 113 (2006) 103-110
44. Roberts R.C., Du F., McCarthy K.E., Okuno E., and Schwarcz R. Immunocytochemical localization of kynurenine aminotransferase in the rat striatum: a light and electron microscopic study. J. Comp. Neurol. 326 (1992) 82-90
45. Rockenstein E., Adame A., Mante M., Larrea G., Crews L., Windisch M., Moessler H., and Masliah E. Amelioration of the cerebrovascular amyloidosis in a transgenic model of Alzheimer's disease with the neurotrophic compound Cerebrolysin™. J. Neural Transm. 112 (2005) 269-282
46. Ruether E., Husmann R., Kinzler E., Diabl E., Klingler D., Spatt J., Ritter R., Schmidt R., Taneri Z., Winterer W., Koper D., Kasper S., and Moessler H. A 28-week, double-blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer's disease. Int. Clin. Psychopharmacol. 16 (2001) 253-263
47. Rüther E., Ritter R., Apecechea M., Freytag S., and Windisch M. Efficacy of the peptidergic nootropic drug cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT). Pharmacopsychiat 27 (1994) 32-40
48. Schmidt W., Guidetti P., Okuno E., and Schwarcz R. Characterization of human brain kynurenine aminotransferases using [3H]kynurenine as a substrate. Neuroscience 55 (1993) 177-184
49. Schwarcz R., Rassoulpour A., Wu H.-Q., Medoff D., Tamminga C.A., and Robert R.C. Increased cortical kynurenate content in schizophrenia. Biol. Psychiatry 50 7 (2001) 521-530
50. Shibata K. Fluorimetric microdetermination of kynurenic acid, an endogenous blocker of neurotoxicity, by high performance liquid chromatography. J. Chromatogr. 430 (1988) 376-380
51. Steele R.J., and Stewart M.G. 7-Chlorokynurenate, an antagonist of the glycine binding site on the NMDA receptor, inhibits memory formation in day-old chicks (Gallus domesticus). Behav. Neural Biol. 60 (1993) 89-92
52. Stone T.W. Neuropharmacology of quinolinic and kynurenic acids. Pharmacol. Rev. 45 (1993) 309-379
53. Swartz K.J., Matson W.R., MacGarvey U., Ryan E.A., and Beal M.F. Measurement of kynurenic acid in mammalian brain extracts and cerebrospinal fluid by high-performance liquid chromatography with fluorometric and coulometric electrode assay detection. Analyt. Biochem. 85 (1990) 363-376
54. Tamburin M., Mostardini M., and Benatti L. Kynurenine aminotransferase I (KAT I) isoform gene expression in the rat brain: an in situ hybridization study. NeuroReport 10 (1999) 61-65
55. Ting K.K., Brew B., and Guillemin G. The involvement of astrocytes and kynurenine pathway in Alzheimer's disease. Neurotox. Res. 12 4 (2007) 247-262
56. Turski W.A., Gramsbergen J.B.P., Traitler H., and Schwarcz R. Rat brain slices produce and liberate kynurenic acid upon expose to l-kynurenine. J. Neurochem. 52 (1989) 1629-1636
57. Valousková V., and Gschane A. Effects of NGF, b-FGF, and cerebrolysin on water maze performance and on motor activity of rats: short- and long-term study. Neurobiol. Learn. Mem. 71 2 (1999) 132-149
58. Veinbergs I., Mante M., Mallory M., and Masliah E. Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity. J. Neural Transm. 59 (2000) 273-280
59. Windisch M., and Piswanger A. Einfluß einer 7tätigen Behandlung mit Cerebrolysin auf die Atmung von Hirnmitochondrien. Neuropsychiatrie 1 2 (1987) 83-88
60. Yu P., Li Z., Zhang L., Tagle D.A., and Cai T. Characterization of kynurenine aminotransferase III, a novel member of a phylogenetically conserved KAT family. Gene 365 (2006) 111-118