Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

  • Fábio B. Mury
  • Weber C. da Silva
  • Nádia R. Barbosa
  • Camila T. Mendes
  • Juliana S. Bonini
  • Jorge Eduardo Souza Sarkis
  • Martin Cammarota
  • Ivan Izquierdo
  • Wagner F. Gattaz
  • Emmanuel Dias-Neto
Original Paper

Abstract

Phospholipase A2 (Pla2) is required for memory retrieval, and its inhibition in the hippocampus has been reported to impair memory acquisition in rats. Moreover, cognitive decline and memory deficits showed to be reduced in animal models after lithium treatment, prompting us to evaluate possible links between Pla2, lithium and memory. Here, we evaluated the possible modulation of Pla2 activity by a long-term treatment of rats with low doses of lithium and its impact in memory. Wistar rats were trained for the inhibitory avoidance task, treated with lithium for 100 days and tested for perdurability of long-term memory. Hippocampal samples were used for quantifying the expression of 19 brain-expressed Pla2 genes and for evaluating the enzymatic activity of Pla2 using group-specific radio-enzymatic assays. Our data pointed to a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer’s disease.

Keywords

Lithium Memory PLA2 Step-down inhibitory avoidance task Hippocampus Gene expression 

Notes

Acknowledgments

The authors acknowledge the support received from Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS), Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP; Grants 04/02165-8, 04/01478-2, 09/52825-8). ED-N is a research fellow from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). WFG acknowledges the support of JNK Empreendimentos e Incorporações given to the Laboratory of Neurosciences (LIM-27). The authors thank Dr. Gustavo Ribeiro Fernandes for his help with data analysis.

Compliance with ethical standards

Conflict of interest

None.

Supplementary material

406_2015_665_MOESM1_ESM.doc (1.6 mb)
Supplementary material 1 (DOC 1621 kb)

References

  1. 1.
    Cade JF (1949) Lithium salts in the treatment of psychotic excitement. Med J Aust 2:349–352PubMedGoogle Scholar
  2. 2.
    Manji HK, Moore GJ, Chen G (2000) Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic-depressive illness. Biol Psychiatry 48:740–754CrossRefPubMedGoogle Scholar
  3. 3.
    Shulman KI, Rochon P, Sykora K, Anderson G et al (2003) Changing prescription patterns for lithium and valproic acid in old age: shifting practice without evidence. BMJ 326:960–961CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Young AH, Newham JI (2006) Lithium in maintenance therapy for bipolar disorder. J Psychopharmacol 20:17–22CrossRefPubMedGoogle Scholar
  5. 5.
    Baldessarini RJ (2002) Treatment research in bipolar disorder: issues and recommendations. CNS Drugs 16:721–729CrossRefPubMedGoogle Scholar
  6. 6.
    Manji HK, Moore GJ, Chen G (1999) Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Biol Psychiatry 46:929–940CrossRefPubMedGoogle Scholar
  7. 7.
    De Strooper B, Woodgett J (2003) Alzheimer’s disease: mental plaque removal. Nature 423:392–393CrossRefPubMedGoogle Scholar
  8. 8.
    Gould TD, Chen G, Manji HK (2004) In vivo evidence in the brain for lithium inhibition of glycogen synthase kinase-3. Neuropsychopharmacol 29:32–38CrossRefGoogle Scholar
  9. 9.
    Mendes CT, Mury FB, de Sa-Moreira E, Alberto FL et al (2009) Lithium reduces Gsk3b mRNA levels: implications for Alzheimer disease. Eur Arch Psychiatry Clin Neurosci 259:16–22CrossRefPubMedGoogle Scholar
  10. 10.
    Phiel CJ, Wilson CA, Lee VM, Klein PS (2003) GSK-3alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature 423:435–439CrossRefPubMedGoogle Scholar
  11. 11.
    Li PP, Young LT, Tam YK, Sibony D, Warsh JJ (1993) Effects of chronic lithium and carbamazepine treatment on G-protein subunit expression in rat cerebral cortex. Biol Psychiatry 34:162–170CrossRefPubMedGoogle Scholar
  12. 12.
    Manji HK, Potter WZ, Lenox RH (1995) Signal transduction pathways. Molecular targets for lithium’s actions. Arch Gen Psychiatry 52:531–543CrossRefPubMedGoogle Scholar
  13. 13.
    Lenox RH, Hahn CG (2000) Overview of the mechanism of action of lithium in the brain: fifty-year update. J Clin Psychiatry 61:5–15PubMedGoogle Scholar
  14. 14.
    Jope RS (1999) Anti-bipolar therapy: mechanism of action of lithium. Mol Psychiatry 4:117–128CrossRefPubMedGoogle Scholar
  15. 15.
    Seelan RS, Khalyfa A, Lakshmanan J, Casanova MF, Parthasarathy RN (2008) Deciphering the lithium transcriptome: microarray profiling of lithium-modulated gene expression in human neuronal cells. Neuroscience 151:1184–1197CrossRefPubMedGoogle Scholar
  16. 16.
    Chen HM, De Long CJ, Bame M, Rajapakse I, Herron TJ, McInnis MG, O’Shea KS (2014) Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients. Transl Psychiatry 4:e375CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Pachet AK, Wisniewski AM (2003) The effects of lithium on cognition: an updated review. Psychopharmacology 170:225–234CrossRefPubMedGoogle Scholar
  18. 18.
    Rockenstein E, Torrance M, Adame A, Mante M et al (2007) Neuroprotective effects of regulators of the glycogen synthase kinase-3 beta signaling pathway in a transgenic model of Alzheimer’s disease are associated with reduced amyloid precursor protein phosphorylation. J Neurosci 27:1981–1991CrossRefPubMedGoogle Scholar
  19. 19.
    Yan XB, Hou HL, Wu LM, Liu J, Zhou JN (2007) Lithium regulates hippocampal neurogenesis by ERK pathway and facilitates recovery of spatial learning and memory in rats after transient global cerebral ischemia. Neuropharmacol 53:487–495CrossRefGoogle Scholar
  20. 20.
    Tsaltas E, Kontis D, Boulougouris V, Papakosta VM et al (2007) Enhancing effects of chronic lithium on memory in the rat. Behav Brain Res 177:51–60CrossRefPubMedGoogle Scholar
  21. 21.
    Nocjar C, Hammonds MD, Shim SS (2007) Chronic lithium treatment magnifies learning in rats. Neuroscience 150:774–788CrossRefPubMedGoogle Scholar
  22. 22.
    Schaeffer EL, Cerulli FG, Souza HO, Catanozi S, Gattaz WF (2014) Synergistic and additive effects of enriched environment and lithium on the generation of new cells in adult mouse hippocampus. J Neural Transm 121:695–706CrossRefPubMedGoogle Scholar
  23. 23.
    Su Y, Ryder J, Li B, Wu X et al (2004) Lithium, a common drug for bipolar disorder treatment, regulates amyloid-beta precursor protein processing. Biochemistry 43:6899–6908CrossRefPubMedGoogle Scholar
  24. 24.
    Kusumo KS, Vaughan M (1977) Effects of lithium salts on memory. Br J Psychiatry 131:453–457CrossRefPubMedGoogle Scholar
  25. 25.
    Lund Y, Nissen M, Rafaelsen OJ (1982) Long-term lithium treatment and psychological functions. Acta Psychiatr Scand 65:233–244CrossRefPubMedGoogle Scholar
  26. 26.
    Squire LR, Judd LL, Janowsky DS, Huey LY (1980) Effects of lithium carbonate on memory and other cognitive functions. Am J Psychiatry 137:1042–1046CrossRefPubMedGoogle Scholar
  27. 27.
    van Gorp WG, Altshuler L, Theberge DC, Wilkins J, Dixon W (1998) Cognitive impairment in euthymic bipolar patients with and without prior alcohol dependence. A preliminary study. Arch Gen Psychiatry 55:41–46CrossRefPubMedGoogle Scholar
  28. 28.
    Calil HM, Zwicker AP, Klepacz S (1990) The effects of lithium carbonate on healthy volunteers: mood stabilization? Biol Psychiatry 27:711–722CrossRefPubMedGoogle Scholar
  29. 29.
    Weingartner H, Rudorfer MV, Linnoila M (1985) Cognitive effects of lithium treatment in normal volunteers. Psychopharmacology 86:472–474CrossRefPubMedGoogle Scholar
  30. 30.
    Nunes PV, Forlenza OV, Gattaz WF (2007) Lithium and risk for Alzheimer’s disease in elderly patients with bipolar disorder. Br J Psychiatry 190:359–360CrossRefPubMedGoogle Scholar
  31. 31.
    Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF (2011) Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment, randomised controlled trial. Br J Psychiatry 198:351–356CrossRefPubMedGoogle Scholar
  32. 32.
    Petersen RC, Caracciolo B, Brayne C, Gauthier S, Jelic V, Fratiglioni L (2014) Mild cognitive impairment: a concept in evolution. J Intern Med 275:214–228CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Bauer M, Alda M, Priller J, Young LT (2003) Implications of the neuroprotective effects of lithium for the treatment of bipolar and neurodegenerative disorders. Pharmacopsychiatry 36:S250–S254CrossRefPubMedGoogle Scholar
  34. 34.
    Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK (2000) Enhancement of hippocampal neurogenesis by lithium. J Neurochem 75:1729–1734CrossRefPubMedGoogle Scholar
  35. 35.
    Dixon JF, Hokin LE (1998) Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. Proc Natl Acad Sci USA 95:8363–8368CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Son H, Yu IT, Hwang SJ, Kim JS et al (2003) Lithium enhances long-term potentiation independently of hippocampal neurogenesis in the rat dentate gyrus. J Neurochem 85:872–881CrossRefPubMedGoogle Scholar
  37. 37.
    Watase K, Gatchel JR, Sun Y, Emamian E et al (2007) Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model. PLoS Med 4:836–847CrossRefGoogle Scholar
  38. 38.
    Gattaz WF, Maras A, Cairns NJ, Levy R, Forstl H (1995) Decreased phospholipase A2 activity in Alzheimer brains. Biol Psychiatry 37:13–17CrossRefPubMedGoogle Scholar
  39. 39.
    Gattaz WF, Cairns NJ, Levy R, Forstl H, Braus DF, Maras A (1996) Decreased phospholipase A2 activity in the brain and in platelets of patients with Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 246:129–131CrossRefPubMedGoogle Scholar
  40. 40.
    Gattaz WF, Levy R, Cairns NJ, Forstl H, Braus DF, Maras A (1996) Relevance of metabolism of membrane phospholipids for Alzheimer dementia. Fortschr Neurol Psychiatr 64:8–12CrossRefPubMedGoogle Scholar
  41. 41.
    Schaeffer EL, Gattaz WF (2007) Requirement of hippocampal phospholipase A2 activity for long-term memory retrieval in rats. J Neural Transm 114:379–385CrossRefPubMedGoogle Scholar
  42. 42.
    Smesny S, Stein S, Willhardt I, Lasch J, Sauer H (2008) Decreased phospholipase A2 activity in cerebrospinal fluid of patients with dementia. J Neural Transm 115:1173–1179CrossRefPubMedGoogle Scholar
  43. 43.
    Talib LL, Yassuda MS, Diniz BS, Forlenza OV, Gattaz WF (2008) Cognitive training increases platelet PLA2 activity in healthy elderly subjects. Prostaglandins Leukot Essent Fatty Acids 78:265–269CrossRefPubMedGoogle Scholar
  44. 44.
    Olfert ED (1993) Guide to the care and use of experimental animals, 2nd edn. Canadian Council on Animal Care, OttawaGoogle Scholar
  45. 45.
    Bernabeu R, Bevilaqua L, Ardenghi P, Bromberg E et al (1997) Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats. Proc Natl Acad Sci USA 94:7041–7046CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Izquierdo LA, Barros DM, Medina JH, Izquierdo I (2003) Exposure to novelty enhances retrieval of very remote memory in rats. Neurobiol Learn Mem 79:51–56CrossRefPubMedGoogle Scholar
  47. 47.
    Da Silva WC, Bonini JS, Bevilaqua LRM, Izquierdo I, Cammarota M (2006) Histamine enhances inhibitory avoidance memory consolidation through a H2 receptor-dependent mechanism. Neurobiol Learn Mem 86:100–106CrossRefPubMedGoogle Scholar
  48. 48.
    Izquierdo LA, Barros DM, Vianna MR, Coitinho A et al (2002) Molecular pharmacological dissection of short- and long-term memory. Cell Mol Neurobiol 22:269–287CrossRefPubMedGoogle Scholar
  49. 49.
    Barros DM, Izquierdo LA, e Souza TM, Ardenghi PG et al (2000) Molecular signalling pathways in the cerebral cortex are required for retrieval of one-trial avoidance learning in rats. Behav Brain Res 114:183–192CrossRefPubMedGoogle Scholar
  50. 50.
    Pellow S, Chopin P, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167CrossRefPubMedGoogle Scholar
  51. 51.
    Chomczynsky P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159Google Scholar
  52. 52.
    Bustin SA, Benes V, Garson JA, Hellemans J et al (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55:611–622CrossRefPubMedGoogle Scholar
  53. 53.
    Vandesompele J, De Preter K, Pattyn F, Poppe B et al (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:1–12CrossRefGoogle Scholar
  54. 54.
    Forlenza OV, Schaeffer EL, Gattaz WF (2002) Phospholipase A2 activity in rat embryonic brain and in primary cultures of cortical neurons. J Neural Transm 109:623–631CrossRefPubMedGoogle Scholar
  55. 55.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  56. 56.
    Farooqui AA, Horrocks LA (2004) Brain phospholipases A2, a perspective on the history. Prostaglandins Leukot Essent Fatty Acids 71:161–169CrossRefPubMedGoogle Scholar
  57. 57.
    Farooqui AA, Yang HC, Horrocks L (1997) Involvement of phospholipase A2 in neurodegeneration. Neurochem Int 30:517–522CrossRefPubMedGoogle Scholar
  58. 58.
    Flesch I, Schmidt B, Ferber E (1985) Acyl chain specificity and kinetic properties of phospholipase A1 and A2 of bone marrow-derived macrophages. Z Naturforsch C 40:356–363PubMedGoogle Scholar
  59. 59.
    Noponen M, Sanfilipo M, Samanich K, Ryer H et al (1993) Elevated PLA2 activity in schizophrenics and other psychiatric patients. Biol Psychiatry 34:641–649CrossRefPubMedGoogle Scholar
  60. 60.
    Ross BM, Moszczynska A, Erlich J, Kish SJ (1998) Phospholipid-metabolizing enzymes in Alzheimer’s disease: increased lysophospholipid acyltransferase activity and decreased phospholipase A2 activity. J Neurochem 70:786–793CrossRefPubMedGoogle Scholar
  61. 61.
    Chalecka-Franaszek E, Chuang DM (1999) Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci USA 96:8745–8750CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Frame S, Cohen P (2001) GSK3 takes centre stage more than 20 years after its discovery. Biochem J 359:1–16CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Hooper C, Killick R, Lovestone S (2008) The GSK3 hypothesis of Alzheimer’s disease. J Neurochem. 104:1433–1439CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Zhang X, Heng X, Li T, Li L, Yang D, Zhang X, Du Y, Doody RS, Le W (2011) Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer’s disease transgenic mouse model. J Alzheimer’s Dis 24:739–749Google Scholar
  65. 65.
    Kessing LV, Forman JL, Andersen PK (2010) Does lithium protect against dementia? Bipolar Disord 12:87–94CrossRefPubMedGoogle Scholar
  66. 66.
    Forlenza OV, de Paula VJ, Machado-Vieira R, Diniz BS, Gattaz WF (2012) Does lithium prevent Alzheimer’s disease? Drugs Aging 29:335–342CrossRefPubMedGoogle Scholar
  67. 67.
    Aprahamian I, Santos FS, Dos Santos B, Talib L, Diniz BS, Radanovic M, Gattaz WF, Forlenza OV (2014) Long-term, low-dose lithium treatment does not impair renal function in the elderly: a 2-year randomized, placebo-controlled trial followed by single-blind extension. J Clin Psychiatry 75:e672–e678CrossRefPubMedGoogle Scholar
  68. 68.
    de Sousa RT, Zanetti MV, Busatto GF, Mouro MG, Zarate CA Jr, Gattaz WF, Higa EM, Machado-Vieira R (2014) Lithium increases nitric oxide levels in subjects with bipolar disorder during depressive episodes. J Psychiatr Res 55:96–100CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Talbot K, Young RA, Jolly-Tornetta C, Lee VM, Trojanowski JQ, Wolf BA (2000) A frontal variant of Alzheimer’s disease exhibits decreased calcium-independent phospholipase A2 activity in the prefrontal cortex. Neurochem Int 37:17–31CrossRefPubMedGoogle Scholar
  70. 70.
    Gattaz WF, Forlenza OV, Talib LL, Barbosa NR, Bottino CM (2004) Platelet phospholipase A(2) activity in Alzheimer’s disease and mild cognitive impairment. J Neural Transm 111:591–601CrossRefPubMedGoogle Scholar
  71. 71.
    Smith LA, Cornelius V, Warnock A, Bell A, Young AH (2007) Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials. Bipolar Disord 9:394–412CrossRefPubMedGoogle Scholar
  72. 72.
    Chuang DM (2004) Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases? Crit Rev Neurobiol 16:83–90CrossRefPubMedGoogle Scholar
  73. 73.
    Gattaz WF, Talib LL, Schaeffer EL, Diniz BS, Forlenza OV (2014) Low platelet iPLA2 activity predicts conversion from mild cognitive impairment to Alzheimer’s disease, a 4-year follow-up study. J Neural Transm 121:193–200CrossRefPubMedGoogle Scholar
  74. 74.
    Schmitt C, Furet Y, Perrotin D, Paintaud G (2009) Acute lithium intoxications, review of the literature and cases study. Therapie 64:55–63CrossRefPubMedGoogle Scholar
  75. 75.
    Chuang DM (2005) The antiapoptotic actions of mood stabilizers: molecular mechanisms and therapeutic potentials. Ann N Y Acad Sci 1053:195–204CrossRefPubMedGoogle Scholar
  76. 76.
    Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006) Learning induces long-term potentiation in the hippocampus. Science 313:1093–1097CrossRefPubMedGoogle Scholar
  77. 77.
    Schaeffer EL, Gattaz WF (2005) Inhibition of calcium-independent phospholipase A2 activity in rat hippocampus impairs acquisition of short- and long-term memory. Psychopharmacology 181:392–400CrossRefPubMedGoogle Scholar
  78. 78.
    Schaeffer EL, Bassi F Jr, Gattaz WF (2005) Inhibition of phospholipase A2 activity reduces membrane fluidity in rat hippocampus. J Neurotransm 112:641–647Google Scholar
  79. 79.
    Rosenberger TA, Villacreses NE, Contreras MA, Bonventre JV, Rapoport SI (2003) Brain lipid metabolism in the cPLA2 knockout mouse. J Lipid Res 44:109–117CrossRefPubMedGoogle Scholar
  80. 80.
    Fujita S, Ikegaya Y, Nishikawa M, Nishiyama N, Matsuki N (2001) Docosahexaenoic acid improves long-term potentiation attenuated by phospholipase A(2) inhibitor in rat hippocampal slices. Br J Pharmacol 132:1417–1422CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39CrossRefPubMedGoogle Scholar
  82. 82.
    Nishizaki T, Nomura T, Matsuoka T, Tsujishita Y (1999) Arachidonic acid as a messenger for the expression of long-term potentiation. Biochem Biophys Res Commun 254:446–449CrossRefPubMedGoogle Scholar
  83. 83.
    Schaeffer EL, Forlenza OV, Gattaz WF (2009) Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease. Psychopharmacology 202:37–51CrossRefPubMedGoogle Scholar
  84. 84.
    Gama MA, Raposo NR, Mury FB, Lopes FC, Dias-Neto E, Talib LL, Gattaz WF (2015) Conjugated linoleic acid-enriched butter improved memory and up-regulated phospholipase A2 encoding-genes in rat brain tissue. J Neural Transm 122:1371–1380CrossRefPubMedGoogle Scholar
  85. 85.
    Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD (2014) Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geriatr Cogn Disord 38:39–45CrossRefPubMedGoogle Scholar
  86. 86.
    Kotani S, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y, Sakakibara M, Yoshimoto T, Guo J, Yamashima T (2006) Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res 56:159–164CrossRefPubMedGoogle Scholar
  87. 87.
    Eckert GP, Schaeffer EL, Schmitt A, Maras A, Gattaz WF (2011) Increased brain membrane fluidity in schizophrenia. Pharmacopsychiatry 44:161–162CrossRefPubMedGoogle Scholar
  88. 88.
    Barbosa NR, Junqueira RM, Vallada HP, Gattaz WF (2007) Association between BanI genotype and increased phospholipase A2 activity in schizophrenia. Eur Arch Psychiatry Clin Neurosci 257:340–343CrossRefPubMedGoogle Scholar
  89. 89.
    Tavares H, Yacubian J, Talib LL, Barbosa NR, Gattaz WF (2003) Increased phospholipase A2 activity in schizophrenia with absent response to niacin. Schizophr Res 61:1–6CrossRefPubMedGoogle Scholar
  90. 90.
    Gattaz WF, Schmitt A, Maras A (1995) Increased platelet phospholipase A2 activity in schizophrenia. Schizophr Res 16:1–6CrossRefPubMedGoogle Scholar
  91. 91.
    Ting C, Rajji TK, Ismail Z, Tang-Wai DF, Apanasiewicz N, Miranda D, Mamo D, Mulsant BH (2010) Differentiating the cognitive profile of schizophrenia from that of Alzheimer disease and depression in late life. Plos One 5:e10151CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Fábio B. Mury
    • 1
    • 2
  • Weber C. da Silva
    • 3
    • 6
  • Nádia R. Barbosa
    • 1
  • Camila T. Mendes
    • 1
    • 2
  • Juliana S. Bonini
    • 3
    • 6
  • Jorge Eduardo Souza Sarkis
    • 4
  • Martin Cammarota
    • 5
  • Ivan Izquierdo
    • 3
  • Wagner F. Gattaz
    • 1
  • Emmanuel Dias-Neto
    • 1
    • 7
  1. 1.Laboratório de Neurociências (LIM27), Instituto de PsiquiatriaFaculdade de Medicina da Universidade de São PauloSão PauloBrazil
  2. 2.Pós-Graduação Interunidades em BiotecnologiaUniversidade de São PauloSão PauloBrazil
  3. 3.Centro de Memória, Instituto de Pesquisas BiomédicasPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  4. 4.Instituto de Pesquisas Energéticas e Nucleares-IPEN-CNEN/SP, Grupo de Caracterização Química e IsotópicaUniversidade de São PauloSão PauloBrazil
  5. 5.Laboratório de Pesquisa de Memória, Instituto do CérebroUniversidade Federal do Rio Grande do NorteNatalBrazil
  6. 6.Departamento de FarmáciaUniversidade Estadual do Centro-OesteGuarapuavaBrazil
  7. 7.Laboratório de Genômica MédicaCentro Internacional de Pesquisas, AC Camargo Cancer CenterSão PauloBrazil

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