N-acetyl cysteine treatment rescues cognitive deficits induced by mitochondrial dysfunction in G72/G30 transgenic mice

Neuropsychopharmacology

Volumn 36, Issue 11, 2011, Pages 2233-2243

  Otte, David Marian ^a   Sommersberg, Britta ^a   Kudin, Alexei ^a   Guerrero, Catalina ^a   Albayram, Önder ^a   Filiou, Michaela D ^b   Frisch, Pamela ^a   Yilmaz, Öznur ^a   Drews, Eva ^a   Turck, Christoph W ^b   Bilkei Gorzó, Andras ^a   Kunz, Wolfram S ^a   Beck, Heinz ^a   Zimmer, Andreas ^a  

^a UNIVERSITY OF BONN   (Germany)

^b MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

Author keywords

G72Tg mice exhibit altered mitochondrial activity and increased production of ROS; G72Tg mice show synaptic deficits and impaired spatial learning; NAC treatment completely restores spatial learning ability in G72Tg mice

Indexed keywords

ACETYLCYSTEINE; GLUTATHIONE DERIVATIVE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE);

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BACTERIAL ARTIFICIAL CHROMOSOME; COGNITIVE DEFECT; CONTROLLED STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; MALE; MEMORY DISORDER; MOUSE; NERVE CELL PLASTICITY; NONHUMAN; PRIORITY JOURNAL; SPATIAL MEMORY; SYNAPSE;

ACETYLCYSTEINE; ANIMALS; CARRIER PROTEINS; COGNITION DISORDERS; ELECTRON TRANSPORT COMPLEX I; HUMANS; MALE; MICE; MICE, TRANSGENIC; MITOCHONDRIAL DISEASES; REACTIVE OXYGEN SPECIES; TREATMENT OUTCOME;

EID: 80052708116     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2011.109     Document Type: Article

References (87)

1. Abou Jamra R, Schmael C, Cichon S, Rietschel M, Schumacher J, Nothen MM (2006). The G72/G30 gene locus in psychiatric disorders: a challenge to diagnostic boundaries? Schizophr Bull 32: 599-608. (Pubitemid 44412845)
2. Addington AM, Gornick M, Sporn AL, Gogtay N, Greenstein D, Lenane M et al (2004). Polymorphisms in the 13q33.2 gene G72/G30 are associated with childhood-onset schizophrenia and psychosis not otherwise specified. Biol psychiatry 55: 976-980. (Pubitemid 38581912)
3. Altar CA, Jurata LW, Charles V, Lemire A, Liu P, Bukhman Y et al (2005). Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts. Biol psychiatry 58: 85-96. (Pubitemid 41008124)
4. Andreazza AC, Shao L, Wang JF, Young LT (2010). Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder. Arch Gen Psychiatry 67: 360-368.
5. Baker DA, McFarland K, Lake RW, Shen H, Toda S, Kalivas PW (2003). N-acetyl cysteine-induced blockade of cocaine-induced reinstatement. Ann N Y Acad Sci 1003: 349-351. (Pubitemid 38083068)
6. Bergmeyer HU, Gawehn K (1970). Methoden der enzymatischen Analyse 2, 2. Aufl. edn. Akademie-Verlag: Berlin. XXXV, 834-1502 S., S. XXXVIII-LXIXpp.
7. Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I et al (2008a). N-acetyl cysteine as a glutathione precursor for schizophreniaFa double-blind, randomized, placebo-controlled trial. Biol Psychiatry 64: 361-368.
8. Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I et al (2008b). N-acetyl cysteine for depressive symptoms in bipolar disorderFa double-blind randomized placebo-controlled trial. Biol Psychiatry 64: 468-475.
9. Board PG (2007). The use of glutathione transferase-knockout mice as pharmacological and toxicological models. Expert Opin Drug Metab Toxicol 3: 421-433. (Pubitemid 47316033)
10. Bottas A, Cooke RG, Richter MA (2005). Comorbidity and pathophysiology of obsessive-compulsive disorder in schizophrenia: is there evidence for a schizo-obsessive subtype of schizophrenia? J Psychiatry Neurosci 30: 187-193. (Pubitemid 40942457)
11. Braff DL, Geyer MA (1990). Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 47: 181-188. (Pubitemid 20058094)
12. Brown MR, Sullivan PG, Geddes JW (2006). Synaptic mitochondria are more susceptible to Ca2+overload than nonsynaptic mitochondria. J Biol Chem 281: 11658-11668. (Pubitemid 43855423)
13. Cataldo AM, McPhie DL, Lange NT, Punzell S, Elmiligy S, Ye NZ et al (2010). Abnormalities in mitochondrial structure in cells from patients with bipolar disorder. Am J Pathol 177: 575-585.
14. Chen CM, Yin MC, Hsu CC, Liu TC (2007). Antioxidative and anti-inflammatory effects of four cysteine-containing agents in striatum of MPTP-treated mice. Nutrition 23: 589-597.
15. Chen HH, Stoker A, Markou A (2010). The glutamatergic compounds sarcosine and N-acetylcysteine ameliorate prepulse inhibition deficits in metabotropic glutamate 5 receptor knockout mice. Psychopharmacology 209: 343-350.
16. Choy KH, Dean O, Berk M, Bush AI, van den Buuse M (2010). Effects of N-acetyl-cysteine treatment on glutathione depletion and a short-term spatial memory deficit in 2-cyclohexene-1-one-treated rats. Eur J Pharmacol 649: 224-228.
17. Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H et al (2002). Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proc Natl Acad Sci USA 99: 13675-13680. (Pubitemid 35215440)
18. D'Aniello A, D'Onofrio G, Pischetola M, D'Aniello G, Vetere A, Petrucelli L et al (1993). Biological role of D-amino acid oxidase and D-aspartate oxidase. Effects of D-amino acids. J Biol Chem 268: 26941-26949. (Pubitemid 24006402)
19. Detera-Wadleigh SD, McMahon FJ (2006). G72/G30 in schizophrenia and bipolar disorder: review and meta-analysis. Biol Psychiatry 60: 106-114. (Pubitemid 44026593)
20. Do KQ, Trabesinger AH, Kirsten-Kruger M, Lauer CJ, Dydak U, Hell D et al (2000). Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci 12: 3721-3728.
21. Esterbauer H, Cheeseman KH (1990). Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxyno-nenal. Methods Enzymol 186: 407-421. (Pubitemid 20279982)
22. Ferrari R, Ceconi C, Curello S, Cargnoni A, Alfieri O, Pardini A et al (1991). Oxygen free radicals and myocardial damage: protective role of thiol-containing agents. Am J Med 91: 95S-105S.
23. Flint DH, Tuminello JF, Emptage MH (1993). The inactivation of Fe-S cluster containing hydro-lyases by superoxide. J Biol Chem 268: 22369-22376. (Pubitemid 23318282)
24. Gardner PR, Nguyen DD, White CW (1994). Aconitase is a sensitive and critical target of oxygen poisoning in cultured mammalian cells and in rat lungs. Proc Natl Acad Sci USA 91: 12248-12252. (Pubitemid 24368642)
25. Goldberg TE, Straub RE, Callicott JH, Hariri A, Mattay VS, Bigelow L et al (2006). The G72/G30 gene complex and cognitive abnormalities in schizophrenia. Neuropsychopharmacology 31: 2022-2032.
26. Grant JE, Odlaug BL, Kim SW (2009). N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry 66: 756-763.
27. Grant SL, Shulman Y, Tibbo P, Hampson DR, Baker GB (2006). Determination of D-serine and related neuroactive amino acids in human plasma by high-performance liquid chromatography with fluorimetric detection. J Chromatogr 844: 278-282. (Pubitemid 44792012)
28. Gysin R, Kraftsik R, Sandell J, Bovet P, Chappuis C, Conus P et al (2007). Impaired glutathione synthesis in schizophrenia: convergent genetic and functional evidence. Proc Natl Acad Sci USA 104: 16621-16626. (Pubitemid 350211066)
29. Hartz SM, Ho BC, Andreasen NC, Librant A, Rudd D, Epping EA et al (2010). G72 influences longitudinal change in frontal lobe volume in schizophrenia. Am J Med Genet B 153B: 640-647.
30. Hayes JD, Flanagan JU, Jowsey IR (2005). Glutathione transferases. Annu Rev Pharmacol Toxicol 45: 51-88. (Pubitemid 40261798)
31. Hayes JD, Pulford DJ (1995). The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30: 445-600.
32. Herken H, Uz E, Ozyurt H, Sogut S, Virit O, Akyol O (2001). Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Mol Psychiatry 6: 66-73. (Pubitemid 32096067)
33. Hopkins RO, Kesner RP, Goldstein M (1995). Item and order recognition memory in subjects with hypoxic brain injury. Brain Cogn 27: 180-201.
34. Iwamoto K, Bundo M, Kato T (2005). Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum Mol Genet 14: 241-253.
35. Jackson-Smith P, Kesner RP, Chiba AA (1993). Continuous recognition of spatial and nonspatial stimuli in hippocampal-lesioned rats. Behav Neural Biol 59: 107-119. (Pubitemid 23131170)
36. Jansen A, Krach S, Krug A, Markov V, Eggermann T, Zerres K et al (2009). A putative high risk diplotype of the G72 gene is in healthy individuals associated with better performance in working memory functions and altered brain activity in the medial temporal lobe. Neuroimage 45: 1002-1008.
37. Jayalakshmi K, Singh SB, Kalpana B, Sairam M, Muthuraju S, Ilavazhagan G (2007). N-acetyl cysteine supplementation prevents impairment of spatial working memory functions in rats following exposure to hypobaric hypoxia. Physiol Behav 92: 643-650. (Pubitemid 350016126)
38. Joyce E, Hutton S, Mutsatsa S, Gibbins H, Webb E, Paul S et al (2002). Executive dysfunction in first-episode schizophrenia and relationship to duration of untreated psychosis: the West London Study. Br J Psychiatry Suppl 43: s38-s44. (Pubitemid 34983511)
39. Kamencic H, Lyon A, Paterson PG, Juurlink BH (2000). Mono-chlorobimane fluorometric method to measure tissue glu-tathione. Anal Biochem 286: 35-37.
40. Kondoh H, Lleonart ME, Bernard D, Gil J (2007). Protection from oxidative stress by enhanced glycolysis; a possible mechanism of cellular immortalization. Histol Histopathol 22: 85-90. (Pubitemid 46117093)
41. Konradi C, Eaton M, MacDonald ML, Walsh J, Benes FM, Heckers S (2004). Molecular evidence for mitochondrial dysfunction in bipolar disorder. Arch Gen Psychiatry 61: 300-308. (Pubitemid 38295832)
42. Korostishevsky M, Kaganovich M, Cholostoy A, Ashkenazi M, Ratner Y, Dahary D et al (2004). Is the G72/G30 locus associated with schizophrenia? Single nucleotide polymorphisms, haplo-types, and gene expression analysis. Biol Psychiatry 56: 169-176. (Pubitemid 38969149)
43. Kudin AP, Bimpong-Buta NY, Vielhaber S, Elger CE, Kunz WS (2004). Characterization of superoxide-producing sites in isolated brain mitochondria. J Biol Chem 279: 4127-4135. (Pubitemid 38198997)
44. Kudin AP, Kudina TA, Seyfried J, Vielhaber S, Beck H, Elger CE et al (2002). Seizure-dependent modulation of mitochondrial oxidative phosphorylation in rat hippocampus. Eur J Neurosci 15: 1105-1114. (Pubitemid 35463612)
45. Kushnareva Y, Murphy AN, Andreyev A (2002). Complex I-mediated reactive oxygen species generation: modulation by cytochrome c and NAD(P)+ oxidation-reduction state. Biochem J 368(Part 2): 545-553. (Pubitemid 35454532)
46. Kvajo M, Dhilla A, Swor DE, Karayiorgou M, Gogos JA (2008). Evidence implicating the candidate schizophrenia/bipolar disorder susceptibility gene G72 in mitochondrial function. Mol Psychiatry 13: 685-696. (Pubitemid 351861528)
47. Lafleur DL, Pittenger C, Kelmendi B, Gardner T, Wasylink S, Malison RT et al (2006). N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology 184: 254-256. (Pubitemid 43084809)
48. LaRowe SD, Mardikian P, Malcolm R, Myrick H, Kalivas P, McFarland K et al (2006). Safety and tolerability of N-acetylcysteine in cocaine-dependent individuals. Am J Addict 15: 105-110. (Pubitemid 43207196)
49. Lavoie S, Murray MM, Deppen P, Knyazeva MG, Berk M, Boulat O et al (2008). Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsycho-pharmacology 33: 2187-2199. (Pubitemid 351992093)
50. Lehmann D, Karussis D, Misrachi-Koll R, Shezen E, Ovadia H, Abramsky O (1994). Oral administration of the oxidant-scavenger N-acetyl-L-cysteine inhibits acute experimental autoimmune encephalomyelitis. J Neuroimmunol 50: 35-42.
51. Li D, He L (2007). G72/G30 genes and schizophrenia: a systematic meta-analysis of association studies. Genetics 175: 917-922. (Pubitemid 46798286)
52. Li Z, Okamoto K, Hayashi Y, Sheng M (2004). The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119: 873-887. (Pubitemid 40017692)
53. Lin CC, Yin MC (2008). Effects of cysteine-containing compounds on biosynthesis of triacylglycerol and cholesterol and anti-oxidative protection in liver from mice consuming a high-fat diet. Br J Nutr 99: 37-43.
54. Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM et al (2002a). 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 USA 99: 2356-2361. (Pubitemid 34169065)
55. Liu Y, Fiskum G, Schubert D (2002b). Generation of reactive oxygen species by the mitochondrial electron transport chain. J Neurochem 80: 780-787. (Pubitemid 34809230)
56. Mahadik SP, Mukherjee S (1996). Free radical pathology and antioxidant defense in schizophrenia: a review. Schizophr Res 19: 1-17. (Pubitemid 26133208)
57. Marchbanks RM, Ryan M, Day IN, Owen M, McGuffin P, Whatley SA (2003). A mitochondrial DNA sequence variant associated with schizophrenia and oxidative stress. Schizophr Res 65: 33-38. (Pubitemid 37410401)
58. Mossner R, Schuhmacher A, Wagner M, Quednow BB, Frommann I, Kuhn KU et al (2010). DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis. Eur Arch Psychiatry Clin Neurosci 260: 209-215.
59. Murray JB (2002). Phencyclidine (PCP): a dangerous drug, but useful in schizophrenia research. J Psychol 136: 319-327.
60. Nguyen AD, Shenton ME, Levitt JJ (2010). Olfactory dysfunction in schizophrenia: a review of neuroanatomy and psychophysio-logical measurements. Harv Rev Psychiatry 18: 279-292.
61. Odlaug BL, Grant JE (2007). N-acetyl cysteine in the treatment of grooming disorders. J Clin Psychopharmacol 27: 227-229. (Pubitemid 46594953)
62. Otte DM, Bilkei-Gorzo A, Filiou MD, Turck CW, Yilmaz O, Holst MI et al (2009). Behavioral changes in G72/G30 transgenic mice. Eur Neuropsychopharmacol 19: 339-348.
63. Palay SL (1956). Synapses in the central nervous system. J Biophys Biochem Cytol 2(Suppl): 193-202.
64. Pollegioni L, Piubelli L, Sacchi S, Pilone MS, Molla G (2007). Physiological functions of D-amino acid oxidases: from yeast to humans. Cell Mol Life Sci 64: 1373-1394. (Pubitemid 46889231)
65. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL et al (2004). Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 9: 684-697, 643. (Pubitemid 38932173)
66. Prata D, Breen G, Osborne S, Munro J, St Clair D, Collier D (2008). Association of DAO and G72(DAOA)/G30 genes with bipolar affective disorder. Am J Med Genet B 147B: 914-917.
67. Sacchi S, Bernasconi M, Martineau M, Mothet JP, Ruzzene M, Pilone MS et al (2008). pLG72 modulates intracellular D-serine levels through its interaction with D-amino acid oxidase: effect on schizophrenia susceptibility. J Biol Chem 283: 22244-22256.
68. Sagara Y, Schubert D (1998). The activation of metabotropic glutamate receptors protects nerve cells from oxidative stress. J Neurosci 18: 6662-6671. (Pubitemid 28387998)
69. Salin PA, Scanziani M, Malenka RC, Nicoll RA (1996). Distinct short-term plasticity at two excitatory synapses in the hippocampus. Proc Natl Acad Sci USA 93: 13304-13309. (Pubitemid 26382811)
70. Schumacher J, Jamra RA, Freudenberg J, Becker T, Ohlraun S, Otte AC et al (2004). Examination of G72 and D-amino-acid oxidase as genetic risk factors for schizophrenia and bipolar affective disorder. Mol Psychiatry 9: 203-207. (Pubitemid 38299535)
71. Shao L, Martin MV, Watson SJ, Schatzberg A, Akil H, Myers RM et al (2008). Mitochondrial involvement in psychiatric disorders. Ann Med 40: 281-295. (Pubitemid 351563935)
72. Sharma R, Yang Y, Sharma A, Awasthi S, Awasthi YC (2004). Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid Redox Signal 6: 289-300. (Pubitemid 38332586)
73. Silberberg G, Wu C, Markram H (2004). Synaptic dynamics control the timing of neuronal excitation in the activated neocortical microcircuit. J Physiol 556(Part 1): 19-27. (Pubitemid 38515166)
74. Sivrioglu EY, Kirli S, Sipahioglu D, Gursoy B, Sarandol E (2007). The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study. Prog Neurop-sychopharmacol Biol Psychiatry 31: 1493-1499. (Pubitemid 47302571)
75. Stork C, Renshaw PF (2005). Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol psychiatry 10: 900-919. (Pubitemid 41486483)
76. Stowers RS, Megeath LJ, Gorska-Andrzejak J, Meinertzhagen IA, Schwarz TL (2002). Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron 36: 1063-1077. (Pubitemid 36044508)
77. Sun X, Wang JF, Tseng M, Young LT (2006). Downregulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder. J Psychiatry Neurosci 31: 189-196. (Pubitemid 43954738)
78. Taylor MA, Berenbaum SA, Jampala VC, Cloninger CR (1993). Are schizophrenia and affective disorder related? Preliminary data from a family study. Am J Psychiatry 150: 278-285. (Pubitemid 23046516)
79. Tsuang MT, Winokur G, Crowe RR (1980). Morbidity risks of schizophrenia and affective disorders among first degree relatives of patients with schizophrenia, mania, depression and surgical conditions. Br J Psychiatry 137: 497-504. (Pubitemid 11251315)
80. Valles V, Van Os J, Guillamat R, Gutierrez B, Campillo M, Gento P et al (2000). Increased morbid risk for schizophrenia in families of in-patients with bipolar illness. Schizophr Res 42: 83-90. (Pubitemid 30163074)
81. Verstreken P, Ly CV, Venken KJ, Koh TW, Zhou Y, Bellen HJ (2005). Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 47: 365-378. (Pubitemid 41073878)
82. Videbech P (2000). PET measurements of brain glucose metabolism and blood flow in major depressive disorder: a critical review. Acta Psychiatr Scand 101: 11-20. (Pubitemid 30041119)
83. Wiedemann FR, Vielhaber S, Schroder R, Elger CE, Kunz WS (2000). Evaluation of methods for the determination of mitochondrial respiratory chain enzyme activities in human skeletal muscle samples. Anal Biochem 279: 55-60. (Pubitemid 30148466)
84. Young LT (2007). Is bipolar disorder a mitochondrial disease? J Psychiatry Neurosci 32: 160-161. (Pubitemid 46903856)
85. Zhang XY, Tan YL, Cao LY, Wu GY, Xu Q, Shen Y et al (2006). Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical antipsychotics. Schizophr Res 81: 291-300. (Pubitemid 43107705)
86. Zhang XY, Tan YL, Zhou DF, Cao LY, Wu GY, Haile CN et al (2007). Disrupted antioxidant enzyme activity and elevated lipid peroxidation products in schizophrenic patients with tardive dyskinesia. J Clin Psychiatry 68: 754-760. (Pubitemid 46841859)
87. Zuliani R, Moorhead TW, Job D, McKirdy J, Sussmann JE, Johnstone EC et al (2009). Genetic variation in the G72 (DAOA) gene affects temporal lobe and amygdala structure in subjects affected by bipolar disorder. Bipolar Disord 11: 621-627.