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Valproic acid-mediated inhibition of trimethyltin-induced deficits in memory and learning in the rat does not directly depend on its anti-oxidant properties

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Abstract

Background

Trimethyltin (TMT) acts as a potent neurotoxic compound especially for the hippocampus. The effects of valproic acid (VPA) on TMT-induced learning and memory deficits were investigated.

Methods

The rats were divided into: (1) control, (2) TMT, (3) TMT–VPA 1, (4) TMT–VPA 5, (5) TMT–VPA 10. TMT was injected as a single dose (12 mg/kg, ip) in groups 2–5. The animals of groups 3–5 were treated by 1, 5, and 10 mg/kg of VPA for 2 weeks. Learning and memory deficits were assessed by Morris water maze (MWM) and passive avoidance (PA) tests. The markers of oxidative stress mainly malondialdehyde (MDA) level and total thiol content were measured in the brain regions.

Results

In MWM test, escape latency and traveled path in the TMT group were higher than control (p < 0.05 and p < 0.01). Treatment by 1, 5, and 10 mg/kg of VPA reduced escape latency and traveled path (p < 0.01–p < 0.001). In PA test, the time latency to enter the dark compartment in TMT group was lower than control group (p < 0.01). Treatment by 5 and 10 mg/kg of VPA increased the time latency (p < 0.05–p < 0.001). MDA concentration in hippocampal tissues of TMT group was higher while, total thiol content was lower than control ones (p < 0.05). Pretreatment with 10 mg/kg of VPA decreased the MDA level while, increased total thiol content (p < 0.01).

Conclusions

The results of present study showed that VPA attenuates TMT-induced memory deficits. Protective effects against brain tissues oxidative damage might have a role in the beneficial effects of VPA.

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References

  1. Corvino V, Marchese E, Giannetti S et al (2012) The neuroprotective and neurogenic effects of neuropeptide Y administration in an animal model of hippocampal neurodegeneration and temporal lobe epilepsy induced by trimethyltin. J Neurochem 122(2):415–426

    Article  PubMed  CAS  Google Scholar 

  2. Earley B, Burke M, Leonard BE (1992) Behavioural, biochemical and histological effects of trimethyltin (TMT) induced brain damage in the rat. Neurochem Int 21(3):351–366

    Article  PubMed  CAS  Google Scholar 

  3. Messing RB, Devauges V, Sara SJ (1992) Limbic forebrain toxin trimethyltin reduces behavioral suppression by clonidine. Pharmacol Biochem Behav 42(2):313–316

    Article  PubMed  CAS  Google Scholar 

  4. Ishida N, Akaike M, Tsutsumi S et al (1997) Trimethyltin syndrome as a hippocampal degeneration model: temporal changes and neurochemical features of seizure susceptibility and learning impairment. Neuroscience 81(4):1183–1191

    Article  PubMed  CAS  Google Scholar 

  5. Wu X, Glinn MA, Ostrowski NL et al (1999) Raloxifene and estradiol benzoate both fully restore hippocampal choline acetyltransferase activity in ovariectomized rats. Brain Res 847(1):98–104

    Article  PubMed  CAS  Google Scholar 

  6. Rabbani O, Panickar KS, Rajakumar G et al (1997) 17 beta-estradiol attenuates fimbrial lesion-induced decline of ChAT-immunoreactive neurons in the rat medial septum. Exp Neurol 146(1):179–186

    Article  PubMed  CAS  Google Scholar 

  7. Chen G, Chen KS, Knox J et al (2000) A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer’s disease. Nature 408(6815):975–979

    Article  PubMed  CAS  Google Scholar 

  8. Kim JK, Choi SJ, Bae H et al (2011) Effects of methoxsalen from Poncirus trifoliata on acetylcholinesterase and trimethyltin-induced learning and memory impairment. Biosci Biotechnol Biochem 75(10):1984–1989

    Article  PubMed  CAS  Google Scholar 

  9. Bielecka AM, Obuchowicz E (2008) Antiapoptotic action of lithium and valproate. Pharmacol Rep 60(6):771–782

    PubMed  CAS  Google Scholar 

  10. Chen PS, Wang C-C, Bortner CD et al (2007) Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity. Neuroscience 149(1):203–212

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Brichta L, Holker I, Haug K, Klockgether T, Wirth B (2006) In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate. Ann Neurol 59(6):970–975

    Article  PubMed  CAS  Google Scholar 

  12. Cui S-S, Yang CP, Bowen RC et al (2003) Valproic acid enhances axonal regeneration and recovery of motor function after sciatic nerve axotomy in adult rats. Brain Res 975(1):229–236

    Article  PubMed  CAS  Google Scholar 

  13. Dash PK, Orsi SA, Zhang M et al (2010) Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. PLoS ONE 5(6):e11383

    Article  PubMed  PubMed Central  Google Scholar 

  14. Feng H-L, Leng Y, Ma C-H, Zhang J, Ren M, Chuang D-M (2008) Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model. Neuroscience 155(3):567–572

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Kim HJ, Rowe M, Ren M, Hong J-S, Chen P-S, Chuang D-M (2007) Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action. J Pharmacol Exp Ther 321(3):892–901

    Article  PubMed  CAS  Google Scholar 

  16. Ren M, Leng Y, Jeong M, Leeds PR, Chuang DM (2004) Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction. J Neurochem 89(6):1358–1367

    Article  PubMed  CAS  Google Scholar 

  17. Rouaux C, Panteleeva I, René F et al (2007) Sodium valproate exerts neuroprotective effects in vivo through CREB-binding protein-dependent mechanisms but does not improve survival in an amyotrophic lateral sclerosis mouse model. J Neurosci 27(21):5535–5545

    Article  PubMed  CAS  Google Scholar 

  18. Sinn D-I, Kim S-J, Chu K et al (2007) Valproic acid-mediated neuroprotection in intracerebral hemorrhage via histone deacetylase inhibition and transcriptional activation. Neurobiol Dis 26(2):464–472

    Article  PubMed  CAS  Google Scholar 

  19. Sugai F, Yamamoto Y, Miyaguchi K et al (2004) Benefit of valproic acid in suppressing disease progression of ALS model mice. Eur J Neurosci 20(11):3179–3183

    Article  PubMed  Google Scholar 

  20. Tsai L-K, Tsai M-S, Ting C-H, Li H (2008) Multiple therapeutic effects of valproic acid in spinal muscular atrophy model mice. J Mol Med 86(11):1243–1254

    Article  PubMed  CAS  Google Scholar 

  21. Zhang Z, Zhang Z, Fauser U, Schluesener H (2008) Valproic acid attenuates inflammation in experimental autoimmune neuritis. Cell Mol Life Sci 65(24):4055–4065

    Article  PubMed  CAS  Google Scholar 

  22. Wang Z, Zhang XJ, Li T, Li J, Tang Y, Le W (2014) Valproic acid reduces neuritic plaque formation and improves learning deficits in APP(Swe)/PS1(A246E) transgenic mice via preventing the prenatal hypoxia-induced down-regulation of neprilysin. CNS Neurosci Ther 20(3):209–217

    Article  PubMed  Google Scholar 

  23. Long Z, Zheng M, Zhao L et al (2013) Valproic acid attenuates neuronal loss in the brain of APP/PS1 double transgenic Alzheimers disease mice model. Curr Alzheimer Res 10(3):261–269

    Article  PubMed  CAS  Google Scholar 

  24. Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 276(39):36734–36741

    Article  PubMed  CAS  Google Scholar 

  25. Peleg S, Sananbenesi F, Zovoilis A et al (2010) Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328(5979):753–756

    Article  PubMed  CAS  Google Scholar 

  26. Guan J-S, Haggarty SJ, Giacometti E et al (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459(7243):55–60

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Gräff J, Rei D, Guan J-S et al (2012) An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 483(7388):222–226

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lv L, Sun Y, Han X, Xu C-c, Tang Y-P, Dong Q (2011) Valproic acid improves outcome after rodent spinal cord injury: potential roles of histone deacetylase inhibition. Brain Res 1396:60–68

    Article  PubMed  CAS  Google Scholar 

  29. Gräff J, Tsai L-H (2013) Histone acetylation: molecular mnemonics on the chromatin. Nat Rev Neurosci 14(2):97–111

    Article  PubMed  Google Scholar 

  30. Fukuchi M, Nii T, Ishimaru N et al (2009) Valproic acid induces up-or down-regulation of gene expression responsible for the neuronal excitation and inhibition in rat cortical neurons through its epigenetic actions. J Neurosci Res 65(1):35–43

    Article  CAS  Google Scholar 

  31. Jeong MR, Hashimoto R, Senatorov VV et al (2003) Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death: a role of histone deacetylase inhibition. FEBS Lett 542(1):74–78

    Article  PubMed  CAS  Google Scholar 

  32. Kanai H, Sawa A, Chen R, Leeds P, Chuang D (2004) Valproic acid inhibits histone deacetylase activity and suppresses excitotoxicity-induced GAPDH nuclear accumulation and apoptotic death in neurons. Pharmacogenomics J 4(5):336–344

    Article  PubMed  CAS  Google Scholar 

  33. Noh H, Seo H (2014) Age-dependent effects of valproic acid in Alzheimer’s disease (AD) mice are associated with nerve growth factor (NGF) regulation. Neuroscience 266:255–265

    Article  PubMed  CAS  Google Scholar 

  34. Kidd SK, Schneider JS (2011) Protective effects of valproic acid on the nigrostriatal dopamine system in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neuroscience 194:189–194

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11(1):47–60

    Article  PubMed  CAS  Google Scholar 

  36. Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1(2):848–858

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hosseini M, Dastghaib SS, Rafatpanah H, Hadjzadeh MA, Nahrevanian H, Farrokhi I (2010) Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth. Clinics 65(11):1175–1181

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hosseini M, Nemati Karimooy HA, Hadjzadeh MA, Safari V (2011) Inducible nitric oxide synthase inhibitor aminoguanidine, differently affects Morris water maze tasks of ovariectomized and naive female rats. Acta Physiol Hung 98(4):421–432

    Article  PubMed  CAS  Google Scholar 

  39. Khodabandehloo F, Hosseini M, Rajaei Z, Soukhtanloo M, Farrokhi E, Rezaeipour M (2013) Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats. Arq Neuropsiquiatr 71(5):313–319

    Article  PubMed  Google Scholar 

  40. Naghibi SM, Hosseini M, Khani F et al (2012) Effect of aqueous extract of Crocus sativus L on morphine-induced memory impairment. Adv Pharmacol Sci 494367

  41. Geloso MC, Corvino V, Michetti F (2011) Trimethyltin-induced hippocampal degeneration as a tool to investigate neurodegenerative processes. Neurochem Int 58(7):729–738

    Article  PubMed  CAS  Google Scholar 

  42. Reuhl KR, Gilbert SG, Mackenzie BA, Mallett JE, Rice DC (1985) Acute trimethyltin intoxication in the monkey (Macaca fascicularis). Toxicol Appl Pharmacol 79(3):436–452

    Article  PubMed  CAS  Google Scholar 

  43. O’Connell A, Earley B, Leonard BE (1994) Changes in muscarinic (M1 and M2 subtypes) and phencyclidine receptor density in the rat brain following trimethyltin intoxication. Neurochem Int 25(3):243–252

    Article  PubMed  Google Scholar 

  44. O’Connell A, Earley B, Leonard BE (1994) The neuroprotective effect of tacrine on trimethyltin induced memory and muscarinic receptor dysfunction in the rat. Neurochem Int 25(6):555–566

    Article  PubMed  Google Scholar 

  45. Bushnell P, Angell K (1992) Effects of trimethyltin on repeated acquisition (learning) in the radial-arm maze. Neurotoxicology 13(2):429–441

    PubMed  CAS  Google Scholar 

  46. Woodruff ML, Baisden RH, Cannon RL, Kalbfleisch J, Freeman JN (1994) Effects of trimethyltin on acquisition and reversal of a light–dark discrimination by rats. Physiol Behav 55(6):1055–1061

    Article  PubMed  CAS  Google Scholar 

  47. D’Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 36(1):60–90

    Article  PubMed  Google Scholar 

  48. Azizi-Malekabadi H, Hosseini M, Soukhtanloo M, Sadeghian R, Fereidoni M, Khodabandehloo F (2012) Different effects of scopolamine on learning, memory, and nitric oxide metabolite levels in hippocampal tissues of ovariectomized and Sham-operated rats. Arq Neuropsiquiatr 70(6):447–452

    Article  PubMed  Google Scholar 

  49. Davoodi FG, Motamedi F, Akbari E, Ghanbarian E, Jila B (2011) Effect of reversible inactivation of reuniens nucleus on memory processing in passive avoidance task. Behav Brain Res 221(1):1–6

    Article  PubMed  Google Scholar 

  50. Kutscher CL (1992) A morphometric analysis of trimethyltin-induced change in rat brain using the Timm technique. Brain Res Bull 28(4):519–527

    Article  PubMed  CAS  Google Scholar 

  51. Tsutsumi S, Akaike M, Arimitsu H, Imai H, Kato N (2002) Circulating corticosterone alters the rate of neuropathological and behavioral changes induced by trimethyltin in rats. Exp Neurol 173(1):86–94

    Article  PubMed  CAS  Google Scholar 

  52. Imai H, Nishimura T, Sadamatsu M, Liu Y, Kabuto M, Kato N (2001) Type II glucocorticoid receptors are involved in neuronal death and astrocyte activation induced by trimethyltin in the rat hippocampus. Exp Neurol 171(1):22–28

    Article  PubMed  CAS  Google Scholar 

  53. Liu Y, Imai H, Sadamatsu M, Tsunashima K, Kato N (2005) Cytokines participate in neuronal death induced by trimethyltin in the rat hippocampus via type II glucocorticoid receptors. Neurosci Res 51(3):319–327

    Article  PubMed  CAS  Google Scholar 

  54. Nakazawa K, McHugh TJ, Wilson MA, Tonegawa S (2004) NMDA receptors, place cells and hippocampal spatial memory. Nat Rev Neurosci 5(5):361–372

    Article  PubMed  CAS  Google Scholar 

  55. Gunasekar PG, Mickova V, Kotyzova D et al (2001) Role of astrocytes in trimethyltin neurotoxicity. J Biochem Mol Toxicol 15(5):256–262

    Article  PubMed  CAS  Google Scholar 

  56. Gunasekar P, Li L, Prabhakaran K, Eybl V, Borowitz JL, Isom GE (2001) Mechanisms of the apoptotic and necrotic actions of trimethyltin in cerebellar granule cells. Toxicol Sci 64(1):83–89

    Article  PubMed  CAS  Google Scholar 

  57. Jenkins SM, Barone S (2004) The neurotoxicant trimethyltin induces apoptosis via caspase activation, p38 protein kinase, and oxidative stress in PC12 cells. Toxicol Lett 147(1):63–72

    Article  PubMed  CAS  Google Scholar 

  58. Patel M, Ardelt BK, Yim GK, Isom GE (1990) Interaction of trimethyltin with hippocampal glutamate. Neurotoxicology 11(4):601–608

    PubMed  CAS  Google Scholar 

  59. Shin EJ, Suh SK, Lim YK et al (2005) Ascorbate attenuates trimethyltin-induced oxidative burden and neuronal degeneration in the rat hippocampus by maintaining glutathione homeostasis. Neuroscience 133(3):715–727

    Article  PubMed  CAS  Google Scholar 

  60. Melloni RH Jr, Apostolides PJ, Hamos JE, DeGennaro LJ (1994) Dynamics of synapsin I gene expression during the establishment and restoration of functional synapses in the rat hippocampus. Neuroscience 58(4):683–703

    Article  PubMed  CAS  Google Scholar 

  61. Andersson H, Radesäter A-C, Luthman J (1995) Trimethyltin-induced loss of NMDA and kainate receptors in the rat brain. J Amino Acids 8(1):23–35

    Article  CAS  Google Scholar 

  62. Brock TO, O’Callaghan JP (1987) Quantitative changes in the synaptic vesicle proteins synapsin I and p38 and the astrocyte-specific protein glial fibrillary acidic protein are associated with chemical-induced injury to the rat central nervous system. J Neurosci 7(4):931–942

    PubMed  CAS  Google Scholar 

  63. Huong NQ, Nakamura Y, Kuramoto N et al (2011) Indomethacin ameliorates trimethyltin-induced neuronal damage in vivo by attenuating oxidative stress in the dentate gyrus of mice. Biol Pharm Bull 34(12):1856–1863

    Article  PubMed  Google Scholar 

  64. Kaur S, Chhabra R, Nehru B (2013) Ginkgo biloba extract attenuates hippocampal neuronal loss and cognitive dysfunction resulting from trimethyltin in mice. Phytomedicine 20(2):178–186

    Article  PubMed  CAS  Google Scholar 

  65. Shin E-J, Nah SY, Kim W-K et al (2005) The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via sigma1 receptor activation: comparison with the effects of dextromethorphan. Br J Pharmacol 144(7):908–918

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  66. Zhang L, Li L, Prabhakaran K, Borowitz JL, Isom GE (2006) Trimethyltin induced apoptosis is associated with upregulation of inducible nitric oxide synthase and Bax in a hippocampal cell line. Toxicol Appl Pharmacol 216:34–43

    Article  PubMed  CAS  Google Scholar 

  67. Harry GJ, Sills R, Schlosser MJ, Maier WE (2001) Neurodegeneration and glia response in rat hippocampus following nitro-l-arginine methyl ester (L-NAME). Neurotox Res 3(3):307–319

    Article  PubMed  CAS  Google Scholar 

  68. Kaur S, Nehru B (2013) Alteration in glutathione homeostasis and oxidative stress during the sequelae of trimethyltin syndrome in rat brain. Biol Trace Elem Res 153(1–3):299–308

    Article  PubMed  CAS  Google Scholar 

  69. Bruccoleri A, Brown H, Harry GJ (1998) Cellular localization and temporal elevation of tumor necrosis factor-alpha, interleukin-1 alpha, and transforming growth factor-beta 1 mRNA in hippocampal injury response induced by trimethyltin. J Neurochem 71(4):1577–1587

    Article  PubMed  CAS  Google Scholar 

  70. Fiedorowicz A, Figiel I, Kaminska B, Zaremba M, Wilk S, Oderfeld-Nowak B (2001) Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure. Brain Res 912(2):116–127

    Article  PubMed  CAS  Google Scholar 

  71. Shirakawa T, Nakano K, Hachiya NS, Kato N, Kaneko K (2007) Temporospatial patterns of COX-2 expression and pyramidal cell degeneration in the rat hippocampus after trimethyltin administration. J Neurosci Res 59(2):117–123

    Article  CAS  Google Scholar 

  72. Reali C, Scintu F, Pillai R, Donato R, Michetti F, Sogos V (2005) S100b counteracts effects of the neurotoxicant trimethyltin on astrocytes and microglia. J Neurosci Res 81(5):677–686

    Article  PubMed  CAS  Google Scholar 

  73. Harry GJ, Tyler K, d’Hellencourt CL, Tilson HA, Maier WE (2002) Morphological alterations and elevations in tumor necrosis factor-alpha, interleukin (IL)-1alpha, and IL-6 in mixed glia cultures following exposure to trimethyltin: modulation by proinflammatory cytokine recombinant proteins and neutralizing antibodies. Toxicol Appl Pharmacol 180(3):205–218

    Article  PubMed  CAS  Google Scholar 

  74. Brabeck C, Michetti F, Geloso MC, Corvino V, Goezalan F, Meyermann R et al (2002) Expression of EMAP-II by activated monocytes/microglial cells in different regions of the rat hippocampus after trimethyltin-induced brain damage. Exp Neurol 177(1):341–346

    Article  PubMed  CAS  Google Scholar 

  75. Pompili E, Nori SL, Geloso MC et al (2004) Trimethyltin-induced differential expression of PAR subtypes in reactive astrocytes of the rat hippocampus. Brain Res Mol Brain Res 122(1):93–98

    Article  PubMed  CAS  Google Scholar 

  76. Lee JY, Maeng S, Kang S et al (2014) Valproic acid protects motor neuron death by inhibiting oxidative stress and ER stress-mediated cytochrome c release after spinal cord injury. J Neurotrauma 31(6):582–594

    Article  PubMed  PubMed Central  Google Scholar 

  77. Suda S, Katsura K, Kanamaru T, Saito M, Katayama Y (2013) Valproic acid attenuates ischemia-reperfusion injury in the rat brain through inhibition of oxidative stress and inflammation. Eur J Pharmacol 707(1–3):26–31

    Article  PubMed  CAS  Google Scholar 

  78. Kabakus N, Ay I, Aysun S, Söylemezoglu F, Özcan A, Celasun B (2005) Protective effects of valproic acid against hypoxic-ischemic brain injury in neonatal rats. J Child Neurol 20(7):582–587

    PubMed  Google Scholar 

  79. Shakespear MR, Halili MA, Irvine KM, Fairlie DP, Sweet MJ (2011) Histone deacetylases as regulators of inflammation and immunity. Trends Immunol 32(7):335–343

    Article  PubMed  CAS  Google Scholar 

  80. Kazantsev AG, Thompson LM (2008) Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov 7(10):854–868

    Article  PubMed  CAS  Google Scholar 

  81. Takebe M, Oishi H, Taguchi K et al (2014) Inhibition of histone deacetylases protects septic mice from lung and splenic apoptosis. J Surg Res 187(2):559–570

    Article  PubMed  CAS  Google Scholar 

  82. Kidd SK, Schneider JS (2010) Protective effects of valproic acid on the nigrostriatal dopamine system in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Brain Res 1354:172–178

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  83. Yuan P-X, Huang L-D, Jiang Y-M, Gutkind JS, Manji HK, Chen G (2001) The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth. J Biol Chem 276(34):31674–31683

    Article  PubMed  CAS  Google Scholar 

  84. Wu J, Dong L, Zhang M et al (2013) Class I histone deacetylase inhibitor valproic acid reverses cognitive deficits in a mouse model of septic encephalopathy. Neurochem Res 38(11):2440–2449

    Article  PubMed  CAS  Google Scholar 

  85. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai L-H (2007) Recovery of learning and memory is associated with chromatin remodelling. Nature 447(7141):178–182

    Article  PubMed  CAS  Google Scholar 

  86. Faraco G, Pancani T, Formentini L et al (2006) Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain. Mol Pharmacol 70(6):1876–1884

    Article  PubMed  CAS  Google Scholar 

  87. Yildirim F, Gertz K, Kronenberg G et al (2008) Inhibition of histone deacetylation protects wildtype but not gelsolin-deficient mice from ischemic brain injury. Exp Neurol 210(2):531–542

    Article  PubMed  CAS  Google Scholar 

  88. Devi L, Ohno M (2011) 7, 8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of Alzheimer’s disease. Neuropsychopharmacology 37(2):434–444

    Article  PubMed  PubMed Central  Google Scholar 

  89. Diógenes MJ, Costenla AR, Lopes LV, Jerónimo-Santos A, Sousa VC, Fontinha BM et al (2011) Enhancement of LTP in aged rats is dependent on endogenous BDNF. Neuropsychopharmacology 36(9):1823–1836

    Article  PubMed  PubMed Central  Google Scholar 

  90. Zeng Y, Tan M, Kohyama J et al (2011) Epigenetic enhancement of BDNF signaling rescues synaptic plasticity in aging. J Neurosci 31(49):17800–17810

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  91. Jacobsen JS, Comery TA, Martone RL et al (2008) Enhanced clearance of Aβ in brain by sustaining the plasmin proteolysis cascade. Proc Natl Acad Sci USA 105(25):8754–8759

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  92. Smith A, Gibbons H, Dragunow M (2010) Valproic acid enhances microglial phagocytosis of amyloid-beta(1-42). Neuroscience 169(1):505–515

    Article  PubMed  CAS  Google Scholar 

  93. Ishimaru F, Shipp M (1995) Analysis of the human CD10/neutral endopeptidase 24.11 promoter region: two separate regulatory elements. Blood 85(11):3199–3207

    PubMed  CAS  Google Scholar 

  94. Nuutinen T, Suuronen T, Kauppinen A, Salminen A (2010) Valproic acid stimulates clusterin expression in human astrocytes: implications for Alzheimer’s disease. Neurosci Lett 475(2):64–68

    Article  PubMed  CAS  Google Scholar 

  95. Hu J-P, Xie J-W, Wang C-Y et al (2011) Valproate reduces tau phosphorylation via cyclin-dependent kinase 5 and glycogen synthase kinase 3 signaling pathways. Brain Res Bull 85(3):194–200

    Article  PubMed  CAS  Google Scholar 

  96. Ximenes JCM, de Oliveira Gonçalves D, Siqueira RMP, et al. (2013) Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties. Naunyn Schmiedebergs Arch Pharmacol, 1–13

  97. Go HS, Seo JE, Kim KC et al (2011) Valproic acid inhibits neural progenitor cell death by activation of NF-B signaling pathway and up-regulation of Bcl-XL. J Biomed Sci 18(1):48

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  98. Li Y, Yuan Z, Liu B et al (2008) Prevention of hypoxia-induced neuronal apoptosis through histone deacetylase inhibition. J Trauma Acute Care Surg 64(4):863–871

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the Vice Presidency of Research of Mashhad University of Medical Sciences for financial support.

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Authors and Affiliations

  1. Department of Biology, Faculty of Basic Sciences, Fars Science and Research Branch, Islamic Azad University, Shiraz, Iran

    M. A. Edalatmanesh & S. Golestani

  2. Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    M. Hosseini & H. R. Sadeghnia

  3. Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    M. Hosseini, S. Ghasemi & F. Vafaee

  4. Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    M. Hosseini & S. M. Mousavi

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  1. M. A. Edalatmanesh
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  2. M. Hosseini
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Correspondence to M. Hosseini.

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Edalatmanesh, M.A., Hosseini, M., Ghasemi, S. et al. Valproic acid-mediated inhibition of trimethyltin-induced deficits in memory and learning in the rat does not directly depend on its anti-oxidant properties . Ir J Med Sci 185, 75–84 (2016). https://doi.org/10.1007/s11845-014-1224-y

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  • DOI: https://doi.org/10.1007/s11845-014-1224-y

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