Sử Dụng Axit Valproic Mạn Tính Giảm Tín Hiệu NMDA Não Qua Axit Arachidonic Ở Chuột Không Gây Tê

Neurochemical Research - Tập 33 - Trang 2229-2240 - 2008
Mireille Basselin1, Lisa Chang1, Mei Chen1, Jane M. Bell, Stanley I. Rapoport
1Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, USA

Tóm tắt

Bằng chứng cho thấy hoạt động glutamatergic trong não bị tăng cao một cách bệnh lý ở rối loạn lưỡng cực gợi ý rằng các chất ổn định tâm trạng mang tính trị liệu cho căn bệnh này phần nào thông qua việc giảm hoạt động glutamatergic. Hoạt động này có thể liên quan đến chất truyền tin thứ hai, axit arachidonic (AA, 20:4n - 6). Chúng tôi đã kiểm tra giả thuyết này liên quan đến axit valproic (VPA) khi kích thích các thụ thể N-methyl-d-aspartate (NMDA) glutamatergic trong não chuột và đo lường AA cùng các phản ứng liên quan. Một liều NMDA (25 mg/kg i.p.) hoặc dung dịch muối sinh lý không gây co giật đã được tiêm cho các con chuột không gây mê, đã được điều trị i.p. hàng ngày với VPA (200 mg/kg) hoặc dung dịch đối chứng trong 30 ngày. Kỹ thuật định lượng tự phát quang học sau khi truyền tĩnh mạch [1-14C]AA đã được sử dụng để hình ảnh hóa các hệ số tích hợp AA trong các vùng não, phản ánh tín hiệu AA. Ở các con chuột được tiền điều trị bằng dung dịch đối chứng, NMDA so với dung dịch muối sinh lý đã làm tăng đáng kể k* trong 41 trong số 82 vùng não được khảo sát, nhiều trong số đó có mật độ thụ thể NMDA cao, và cũng làm tăng nồng độ não của các chất chuyển hóa AA, prostaglandin E2 (PGE2) và thromboxane B2 (TXB2). Tiền điều trị bằng VPA đã giảm nồng độ nền của PGE2 và TXB2, và chặn lại sự gia tăng do NMDA gây ra trong k* và nồng độ eicosanoid. Những kết quả này, cùng với bằng chứng rằng carbamazepine và lithium cũng chặn phản ứng k* với NMDA trong não chuột, gợi ý rằng các chất ổn định tâm trạng có tác dụng trong rối loạn lưỡng cực một phần thông qua việc giảm tín hiệu glutamatergic liên quan đến AA.

Từ khóa

#rối loạn lưỡng cực #axit valproic #thụ thể NMDA #axit arachidonic #prostaglandin E2 #thromboxane B2

Tài liệu tham khảo

Ahmad S, Fowler LJ, Whitton PS (2005) Effects of combined lamotrigine and valproate on basal and stimulated extracellular amino acids and monoamines in the hippocampus of freely moving rats. Naunyn Schmiedebergs Arch Pharmacol 371:1–8 Anand A, Charney DS, Oren DA et al (2000) Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-d-aspartate receptor antagonists. Arch Gen Psychiatry 57:270–276 Bai G, Kusiak JW (1995) Functional analysis of the proximal 5′-flanking region of the N-methyl-d-aspartate receptor subunit gene, NMDAR1. J Biol Chem 270:7737–7744 Basselin M, Chang L, Bell JM et al (2005) Chronic lithium chloride administration to unanesthetized rats attenuates brain dopamine D2-like receptor-initiated signaling via arachidonic acid. Neuropsychopharmacology 30:1064–1075 Basselin M, Chang L, Bell JM et al (2006) Chronic lithium chloride administration attenuates brain NMDA receptor-initiated signaling via arachidonic acid in unanesthetized rats. Neuropsychopharmacology 31:1659–1674 Basselin M, Chang L, Chen M et al (2008) Chronic carbamazepine administration attenuates dopamine D2-like receptor-initiated signaling via arachidonic acid in rat brain. Neurochem Res. doi:10.1007/s11064-008-9595-y Basselin M, Chang L, Seemann R et al (2003) Chronic lithium administration potentiates brain arachidonic acid signaling at rest and during cholinergic activation in awake rats. J Neurochem 85:1553–1562 Basselin M, Chang L, Seemann R et al (2005) Chronic lithium administration to rats selectively modifies 5-HT2A/2C receptor-mediated brain signaling via arachidonic acid. Neuropsychopharmacology 30:461–472 Basselin M, Villacreses NE, Chen M et al (2007) Chronic carbamazepine administration reduces N-methyl-D-aspartate receptor-initiated signaling via arachidonic acid in rat brain. Biol Psychiatry 62:934–943 Basselin M, Villacreses NE, Langenbach R et al (2006) Resting and arecoline-stimulated brain metabolism and signaling involving arachidonic acid are altered in the cyclooxygenase-2 knockout mouse. J Neurochem 96:669–679 Basselin M, Villacreses NE, Lee HJ et al (2007) Flurbiprofen, a cyclooxygenase inhibitor, reduces the brain arachidonic acid signal in response to the cholinergic muscarinic agonist, arecoline, in awake rats. Neurochem Res 32:1857–1867 Bazinet RP, Weis MT, Rapoport SI et al (2006) Valproic acid selectively inhibits conversion of arachidonic acid to arachidonoyl-CoA by brain microsomal long-chain fatty acyl-CoA synthetases: relevance to bipolar disorder. Psychopharmacology (Berl) 184:122–129 Bosetti F, Bell JM, Manickam P (2005) Microarray analysis of rat brain gene expression after chronic administration of sodium valproate. Brain Res Bull 65:331–338 Bosetti F, Weerasinghe GR, Rosenberger TA et al (2003) Valproic acid down-regulates the conversion of arachidonic acid to eicosanoids via cyclooxygenase-1 and -2 in rat brain. J Neurochem 85:690–696 Bosisio E, Galli C, Galli G et al (1976) Correlation between release of free arachidonic acid and prostaglandin formation in brain cortex and cerebellum. Prostaglandins 11:773–781 Bowden CL (2003) Valproate. Bipolar Disord 5:189–202 Bowden CL, Karren NU (2006) Anticonvulsants in bipolar disorder. Aust N Z J Psychiatry 40:386–393 Bown CD, Wang JF, Young LT (2003) Attenuation of N-methyl-d-aspartate-mediated cytoplasmic vacuolization in primary rat hippocampal neurons by mood stabilizers. Neuroscience 117:949–955 Bymaster FP, Felder CC (2002) Role of the cholinergic muscarinic system in bipolar disorder and related mechanism of action of antipsychotic agents. Mol Psychiatry 7(suppl 1):S57–S63 Caldeira MV, Melo CV, Pereira DB et al (2007) BDNF regulates the expression and traffic of NMDA receptors in cultured hippocampal neurons. Mol Cell Neurosci 35:208–219 Carli M, Afkhami-Dastjerdian S, Reader TA (1997) Effects of a chronic lithium treatment on cortical serotonin uptake sites and 5-HT1A receptors. Neurochem Res 22:427–435 Chang MC, Contreras MA, Rosenberger TA et al (2001) Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in brain phospholipids: a possible common effect of mood stabilizers. J Neurochem 77:796–803 Chen G, Zeng WZ, Yuan PX et al (1999) The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS. J Neurochem 72:879–882 Cipriani A, Rendell JM, Geddes JR (2006) Haloperidol alone or in combination for acute mania. Cochrane Database Syst Rev 3:CD004362 Cooper JR, Bloom FE, Roth RH (2003) The biochemical basis of neuropharmacology, 8th edn. Oxford University Press, Oxford DeGeorge JJ, Noronha JG, Bell JM et al (1989) Intravenous injection of [1-14C]arachidonate to examine regional brain lipid metabolism in unanesthetized rats. J Neurosci Res 24:413–423 Delaney SM, Geiger JD (1995) Enhancement of NMDA-induced increases in levels of endogenous adenosine by adenosine deaminase and adenosine transport inhibition in rat striatum. Brain Res 702:72–76 DeMar JC Jr, Lee HJ, Ma K et al (2006) Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats. Biochim Biophys Acta 1761:1050–1059 Detich N, Bovenzi V, Szyf M (2003) Valproate induces replication-independent active DNA demethylation. J Biol Chem 278:27586–27592 Deutsch J, Rapoport SI, Purdon AD (1997) Relation between free fatty acid and acyl-CoA concentrations in rat brain following decapitation. Neurochem Res 22:759–765 Dong E, Guidotti A, Grayson DR et al (2007) Histone hyperacetylation induces demethylation of reelin and 67-kDa glutamic acid decarboxylase promoters. Proc Natl Acad Sci USA 104:4676–4681 Du J, Gray NA, Falke CA et al (2004) Modulation of synaptic plasticity by antimanic agents: the role of AMPA glutamate receptor subunit 1 synaptic expression. J Neurosci 24:6578–6589 Dumuis A, Sebben M, Haynes L et al (1988) NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Nature 336:68–70 Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509 Fountoulakis KN, Vieta E, Siamouli M et al (2007) Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder. Ann Gen Psychiatry 6:27 Frey BN, Andreazza AC, Cereser KM et al (2006) Effects of mood stabilizers on hippocampus BDNF levels in an animal model of mania. Life Sci 79:281–286 Gean PW, Huang CC, Hung CR et al (1994) Valproic acid suppresses the synaptic response mediated by the NMDA receptors in rat amygdalar slices. Brain Res Bull 33:333–336 Gobbi G, Janiri L (2006) Sodium- and magnesium-valproate in vivo modulate glutamatergic and GABAergic synapses in the medial prefrontal cortex. Psychopharmacology (Berl) 185:255–262 Goodnick PJ (2006) Anticonvulsants in the treatment of bipolar mania. Expert Opin Pharmacother 7:401–410 Groc L, Choquet D, Stephenson FA et al (2007) NMDA receptor surface trafficking and synaptic subunit composition are developmentally regulated by the extracellular matrix protein Reelin. J Neurosci 27:10165–10175 Hashimoto K, Sawa A, Iyo M (2007) Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 62:1310–1316 Hassel B, Iversen EG, Gjerstad L et al (2001) Up-regulation of hippocampal glutamate transport during chronic treatment with sodium valproate. J Neurochem 77:1285–1292 Johannessen CU (2000) Mechanisms of action of valproate: a commentatory. Neurochem Int 37:103–110 Kábová R, Liptáková S, Slamberová R et al (1999) Age-specific N-methyl-d-aspartate-induced seizures: perspectives for the West syndrome model. Epilepsia 40:1357–1369 Kanai H, Sawa A, Chen RW et al (2004) Valproic acid inhibits histone deacetylase activity and suppresses excitotoxicity-induced GAPDH nuclear accumulation and apoptotic death in neurons. Pharmacogenomics J 4:336–344 Kim DK, Rordorf G, Nemenoff RA et al (1995) Glutamate stably enhances the activity of two cytosolic forms of phospholipase A2 in brain cortical cultures. Biochem J 310(Pt 1):83–90 Ko GY, Brown-Croyts LM, Teyler TJ (1997) The effects of anticonvulsant drugs on NMDA-EPSP, AMPA-EPSP, and GABA-IPSP in the rat hippocampus. Brain Res Bull 42:297–302 Kunig G, Niedermeyer B, Deckert J et al (1998) Inhibition of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA] binding by the anticonvulsant valproate in clinically relevant concentrations: an autoradiographic investigation in human hippocampus. Epilepsy Res 31:153–157 Lambert RC, Bessaih T, Leresche N (2006) Modulation of neuronal T-type calcium channels. CNS Neurol Disord Drug Targets 5:611–627 Lan MJ, McLoughlin GA, Griffin JL et al (2008) Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder. Mol Psychiatry. doi:10.1038/sj.mp.4002130 Lazarewicz JW, Saliñska E, Stafiej A et al (2000) NMDA receptors and nitric oxide regulate prostaglandin D2 synthesis in the rabbit hippocampus in vivo. Acta Neurobiol Exp (Wars) 60:427–435 Lazarewicz JW, Wroblewski JT, Palmer ME et al (1988) Activation of N-methyl-d-aspartate-sensitive glutamate receptors stimulates arachidonic acid release in primary cultures of cerebellar granule cells. Neuropharmacology 27:765–769 Leonard AS, Hell JW (1997) Cyclic AMP-dependent protein kinase and protein kinase C phosphorylate N-methyl-d-aspartate receptors at different sites. J Biol Chem 272:12107–12115 Lerea LS, Carlson NG, Simonato M et al (1997) Prostaglandin F2α is required for NMDA receptor-mediated induction of c-fos mRNA in dentate gyrus neurons. J Neurosci 17:117–124 Li R, Wing LL, Wyatt RJ et al (1993) Effects of haloperidol, lithium, and valproate on phosphoinositide turnover in rat brain. Pharmacol Biochem Behav 46:323–329 Mahmood T, Silverstone T (2001) Serotonin and bipolar disorder. J Affect Disord 66:1–11 Martin ED, Pozo MA (2004) Valproate reduced excitatory postsynaptic currents in hippocampal CA1 pyramidal neurons. Neuropharmacology 46:555–561 Mater MK, Thelen AP, Jump DB (1999) Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression. J Lipid Res 40:1045–1052 McCullumsmith RE, Kristiansen LV, Beneyto M et al (2007) Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder. Brain Res 1127:108–118 Murphy DL, Brodie HK, Goodwin FK et al (1971) Regular induction of hypomania by l-dopa in “bipolar” manic-depressive patients. Nature 229:135–136 Muzina DJ, Elhaj O, Gajwani P et al (2005) Lamotrigine and antiepileptic drugs as mood stabilizers in bipolar disorder. Acta Psychiatr Neurol Scand Suppl:21–28 Nasrallah HA, Ketter TA, Kalali AH (2006) Carbamazepine and valproate for the treatment of bipolar disorder: a review of the literature. J Affect Disord 95:69–78 O′Donnell T, Rotzinger S, Ulrich M et al (2003) Effects of chronic lithium and sodium valproate on concentrations of brain amino acids. Eur Neuropsychopharmacol 13:220–227 Okada S, Murakami Y, Nishihara M et al (2000) Perfusion of the hypothalamic paraventricular nucleus with N-methyl-d-aspartate produces thromboxane A2 and centrally activates adrenomedullary outflow in rats. Neuroscience 96:585–590 Ormandy GC, Song L, Jope RS (1991) Analysis of the convulsant-potentiating effects of lithium in rats. Exp Neurol 111:356–361 Pal R, Eaton MJ, Islam S et al (1999) Immunocytochemical and in situ hybridization studies of the expression and distribution of three subunits of a complex with N-methyl-d-aspartate receptor-like properties. Neuroscience 94:1291–1311 Paxinos G, Watson C (1987) The rat brain in stereotaxic coordinates, Third edn. Academic Press, New York Peet M, Peters S (1995) Drug-induced mania. Drug Saf 12:146–153 Pepicelli O, Fedele E, Bonanno G et al (2002) In vivo activation of N-methyl-d-aspartate receptors in the rat hippocampus increases prostaglandin E2 extracellular levels and triggers lipid peroxidation through cyclooxygenase-mediated mechanisms. J Neurochem 81:1028–1034 Phiel CJ, Zhang F, Huang EY et al (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 276:36734–36741 Post RM, Jimerson DC, Bunney WE Jr et al (1980) Dopamine and mania: behavioral and biochemical effects of the dopamine receptor blocker pimozide. Psychopharmacology (Berl) 67:297–305 Qiang M, Ticku MK (2005) Role of AP-1 in ethanol-induced N-methyl-d-aspartate receptor 2B subunit gene up-regulation in mouse cortical neurons. J Neurochem 95:1332–1341 Rao JS, Bazinet RP, Rapoport SI et al (2007) Chronic treatment of rats with sodium valproate downregulates frontal cortex NF-κB DNA binding activity and COX-2 mRNA. Bipolar Disord 9:513–520 Rapoport SI (2001) In vivo fatty acid incorporation into brain phospholipids in relation to plasma availability, signal transduction and membrane remodeling. J Mol Neurosci 16:243–261 Rapoport SI, Chang MCJ, Spector AA (2001) Delivery and turnover of plasma-derived essential PUFAs in mammalian brain. J Lipid Res 42:678–685 Robinson PJ, Noronha J, DeGeorge JJ et al (1992) A quantitative method for measuring regional in vivo fatty-acid incorporation into and turnover within brain phospholipids: review and critical analysis. Brain Res Brain Res Rev 17:187–214 Rowe MK, Chuang DM (2004) Lithium neuroprotection: molecular mechanisms and clinical implications. Expert Rev Mol Med 6:1–18 Shao L, Young LT, Wang JF (2005) Chronic treatment with mood stabilizers lithium and valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells. Biol Psychiatry 58:879–884 Shen Y, Kishimoto K, Linden DJ et al (2007) Cytosolic phospholipase A2 alpha mediates electrophysiologic responses of hippocampal pyramidal neurons to neurotoxic NMDA treatment. Proc Natl Acad Sci USA 104:6078–6083 Sonnenberg JL, Mitchelmore C, Macgregor-Leon PF et al (1989) Glutamate receptor agonists increase the expression of Fos, Fra, and AP-1 DNA binding activity in the mammalian brain. J Neurosci Res 24:72–80 Stefanovic B, Bosetti F, Silva AC (2006) Modulatory role of cyclooxygenase-2 in cerebrovascular coupling. Neuroimage 32:23–32 Steppuhn KG, Turski L (1993) Modulation of the seizure threshold for excitatory amino acids in mice by antiepileptic drugs and chemoconvulsants. J Pharmacol Exp Ther 265:1063–1070 Stout SC, Owens MJ, Lindsey KP et al (2001) Effects of sodium valproate on corticotropin-releasing factor systems in rat brain. Neuropsychopharmacology 24:624–631 Szupera Z, Mezei Z, Kis B et al (2000) The effects of valproate on the arachidonic acid metabolism of rat brain microvessels and of platelets. Eur J Pharmacol 387:205–210 Tabachnick BG, Fidell LS (2001) Computer-assisted research design and analysis. Allyn and Bacon Ed, Boston Tanaka J, Miyakubo H, Kawakami A et al (2006) Involvement of NMDA receptor mechanisms in the modulation of serotonin release in the lateral parabrachial nucleus in the rat. Brain Res Bull 71:311–315 Tapia-Arancibia L, Rage F, Recasens M et al (1992) NMDA receptor activation stimulates phospholipase A2 and somatostatin release from rat cortical neurons in primary cultures. Eur J Pharmacol 225:253–262 Teng CT, Demetrio FN (2006) Memantine may acutely improve cognition and have a mood stabilizing effect in treatment-resistant bipolar disorder. Rev Bras Psiquiatr 28:252–254 Thurston JH, Hauhart RE (1989) Valproate doubles the anoxic survival time of normal developing mice: possible relevance to valproate-induced decreases in cerebral levels of glutamate and aspartate, and increases in taurine. Life Sci 45:59–62 Toro C, Deakin JF (2005) NMDA receptor subunit NRI and postsynaptic protein PSD-95 in hippocampus and orbitofrontal cortex in schizophrenia and mood disorder. Schizophr Res 80:323–330 Turski L, Niemann W, Stephens DN (1990) Differential effects of antiepileptic drugs and beta-carbolines on seizures induced by excitatory amino acids. Neuroscience 39:799–807 Ueda Y, Willmore LJ (2000) Molecular regulation of glutamate and GABA transporter proteins by valproic acid in rat hippocampus during epileptogenesis. Exp Brain Res 133:334–339 Weichel O, Hilgert M, Chatterjee SS et al (1999) Bilobalide, a constituent of Ginkgo biloba, inhibits NMDA-induced phospholipase A2 activation and phospholipid breakdown in rat hippocampus. Naunyn Schmiedebergs Arch Pharmacol 360:609–615 Wu Y, Wang L (2002) The effects of antiepileptic drugs on spatial learning and hippocampal protein kinase Cγ in immature rats. Brain Dev 24:82–87 Young AM, Bradford HF (1993) N-methyl-d-aspartate releases gamma-aminobutyric acid from rat striatum in vivo: a microdialysis study using a novel preloading method. J Neurochem 60:487–492 Zeise ML, Kasparow S, Zieglgansberger W (1991) Valproate suppresses N-methyl-d-aspartate-evoked, transient depolarizations in the rat neocortex in vitro. Brain Res 544:345–348