1H-Nuclear magnetic resonance-based metabolomic analysis of brain in mice with nicotine treatment

BMC Neuroscience

Xiaobo Cen¹  Yinglan Zhao¹  Qian Bu¹  Dengqi Fu¹  Qian Zhao¹  Changman Du¹  Jing Hou¹  Baolai Zhang¹  Yan Li¹  Ruiming Zhu¹  Yi Deng¹  Zhengtao Hu¹  Xue Shao¹  Bo Chen¹  Hongyu Li¹ 

[1] National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, 28# Gaopeng Avenue, High Technological Development Zone, Chengdu 610041, China

关键词: Place preference;    NMR;    Metabolite;    Nicotine;    Metabolomics;   

Others  :  1122554
DOI  :  10.1186/1471-2202-15-32

 received in 2013-09-08, accepted in 2014-02-18,  发布年份 2014

【 摘 要 】

Background

Nicotine is rapidly absorbed from cigarette smoke and therefore induces a number of chronic illnesses with the widespread use of tobacco products. Studies have shown a few cerebral metabolites modified by nicotine; however, endogenous metabolic profiling in brain has not been well explored.

Results

H NMR-based on metabonomics was applied to investigate the endogenous metabolic profiling of brain hippocampus, nucleus acumens (NAc), prefrontal cortex (PFC) and striatum. We found that nicotine significantly increased CPP in mice, and some specific cerebral metabolites differentially changed in nicotine-treated mice. These modified metabolites included glutamate, acetylcholine, tryptamine, glucose, lactate, creatine, 3-hydroxybutyrate and nicotinamide-adenine dinucleotide (NAD), which was closely associated with neurotransmitter and energy source. Additionally, glutathione and taurine in hippocampus and striatum, phosphocholine in PFC and glycerol in NAc were significantly modified by nicotine, implying the dysregulation of anti-oxidative stress response and membrane metabolism.

Conclusions

Nicotine induces significant metabonomic alterations in brain, which are involved in neurotransmitter disturbance, energy metabolism dysregulation, anti-oxidation and membrane function disruptions, as well as amino acid metabolism imbalance. These findings provide a new insight into rewarding effects of nicotine and the underlying mechanism.

【 授权许可】

   
2014 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Le Foll B, Goldberg SR: Nicotine as a typical drug of abuse in experimental animals and humans. Psychopharmacology 2006, 184(3):367-381.
• [2]Rose JE, Corrigall WA: Nicotine self-administration in animals and humans: similarities and differences. Psychopharmacology 1997, 130(1):28-40.
• [3]DiFranza JR: Hooked from the first cigarette. Sci Am 2008, 298(5):82-87.
• [4]Stead LF, Perera R, Bullen C, Mant D, Lancaster T: Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2008, 1(1):22-28.
• [5]Dajas-Bailador F, Wonnacott S: Nicotinic acetylcholine receptors and the regulation of neuronal signalling. Trends in Pharmacol Sci 2004, 25(6):317-324.
• [6]Greenbaum L, Lerer B: Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions. Mol Psychiatry 2009, 14(10):912-945.
• [7]Govind AP, Vezina P, Green WN: Nicotine-induced upregulation of nicotinic receptors: underlying mechanisms and relevance to nicotine addiction. Biochem Pharmacol 2009, 78(7):756-765.
• [8]Kaddurah-Daouk R, Krishnan KRR: Metabolomics: a global biochemical approach to the study of central nervous system diseases. Neuropsychopharmacology 2008, 34(1):173-186.
• [9]Patkar AA, Rozen S, Mannelli P, Matson W, Pae C-U, Krishnan KR, Kaddurah-Daouk R: Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study. Psychopharmacology 2009, 206(3):479-489.
• [10]Wang-Sattler R, Yu Y, Mittelstrass K, Lattka E, Altmaier E, Gieger C, Ladwig KH, Dahmen N, Weinberger KM, Hao P: Metabolic profiling reveals distinct variations linked to nicotine consumption in humans—first results from the KORA study. PloS one 2008, 3(12):e3863.
• [11]Garrod S, Bollard ME, Nicholls AW, Connor SC, Connelly J, Nicholson JK, Holmes E: Integrated metabonomic analysis of the multiorgan effects of hydrazine toxicity in the rat. Chem Res in Toxicol 2005, 18(2):115-122.
• [12]Jung JY, Lee HS, Kang DG, Kim NS, Cha MH, Bang OS, Hwang GS: 1H-NMR-based metabolomics study of cerebral infarction. Stroke 2011, 42(5):1282-1288.
• [13]Li Y, Yan G, Zhou J, Bu Q, Deng P, Yang Y, Lv L, Deng Y, Zhao J, Shao X: 1H Nmr-based metabonomics in brain nucleus accumbens and striatum following repeated cocaine treatment in rats. Neuroscience 2012, 218:196-205.
• [14]Gao H, Xiang Y, Sun N, Zhu H, Wang Y, Liu M, Ma Y, Lei H: Metabolic changes in rat prefrontal cortex and hippocampus induced by chronic morphine treatment studied by high resolution 1H NMR spectroscopy. Neurochem Int 2007, 50(2):386-394.
• [15]Levine A, Huang Y, Drisaldi B, Griffin EA Jr, Pollak DD, Xu S, Yin D, Schaffran C, Kandel DB, Kandel ER: Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine. Sci Transl Med 2011, 3(107):107-109.
• [16]Brunzell DH, Mineur YS, Neve RL, Picciotto MR: Nucleus accumbens CREB activity is necessary for nicotine conditioned place preference. Neuropsychopharmacology 2009, 34(8):1993-2001.
• [17]Agatsuma S, Lee M, Zhu H, Chen K, Shih JC, Seif I, Hiroi N: Monoamine oxidase A knockout mice exhibit impaired nicotine preference but normal responses to novel stimuli. Human Mol Genet 2006, 15(18):2721-2731.
• [18]Salek R, Colebrooke R, Macintosh R, Lynch P, Sweatman B, Emson P, Griffin J: A metabolomic study of brain tissues from aged mice with low expression of the vesicular monoamine transporter 2 (VMAT2) gene. Neurochem Res 2008, 33(2):292-300.
• [19]Pears M, Cooper J, Mitchison H, Mortishire-Smith R, Pearce D, Griffin J: High resolution 1H NMR-based metabolomics indicates a neurotransmitter cycling deficit in cerebral tissue from a mouse model of Batten disease. J Biol Chem 2005, 280(52):42508.
• [20]Nicholson JK, Connelly J, Lindon JC, Holmes E: Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 2002, 1(2):153-162.
• [21]Brindle JT, Antti H, Holmes E, Tranter G, Nicholson JK, Bethell HWL, Clarke S, Schofield PM, McKilligin E, Mosedale DE: Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nat Med 2002, 8(12):1439-1445.
• [22]Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, Cheng D, Jewell K, Arndt D, Sawhney S: HMDB: the human metabolome database. Nucleic acids Res 2007, 35(suppl 1):D521-D526.
• [23]Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E, Lindon JC, Nicholson JK: Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat protocols 2007, 2(11):2692-2703.
• [24]Nicholson JK, Lindon JC: Systems biology: metabonomics. Nature 2008, 455(7216):1054-1056.
• [25]Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H, Kinoshita T, Saito N, Ochiai A, Tomita M: Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res 2009, 69(11):4918-4925.
• [26]Summers K, Giacobini E: Effects of local and repeated systemic administration of (-) nicotine on extracellular levels of acetylcholine, norepinephrine, dopamine, and serotonin in rat cortex. Neurochem Res 1995, 20(6):753-759.
• [27]Toth E, Sershen H, Hashim A, Vizi E, Lajtha A: Effect of nicotine on extracellular levels of neurotransmitters assessed by microdialysis in various brain regions: role of glutamic acid. Neurochem Res 1992, 17(3):265-271.
• [28]Zanetti L, Picciotto MR, Zoli M: Differential effects of nicotinic antagonists perfused into the nucleus accumbens or the ventral tegmental area on cocaine-induced dopamine release in the nucleus accumbens of mice. Psychopharmacology 2007, 190(2):189-199.
• [29]Vezina P, McGehee D, Green W: Exposure to nicotine and sensitization of nicotine-induced behaviors. Prog Neuro-Psychopharmacol Biol Psychiatry 2007, 31(8):1625-1638.
• [30]Kalivas PW, LaLumiere RT, Knackstedt L, Shen H: Glutamate transmission in addiction. Neuropharmacology 2009, 56:169-173.
• [31]Uys JD, LaLumiere RT: Glutamate: the new frontier in pharmacotherapy for cocaine addiction. CNS & Neurol Dis-Drug Targets 2008, 7(5):482-491.
• [32]Kashkin VA, De Witte P: Nicotine increases microdialysate brain amino acid concentrations and induces conditioned place preference. Eur Neuropsychopharmacol 2005, 15(6):625-632.
• [33]Kenney JW, Gould TJ: Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol Neurobiol 2008, 38(1):101-121.
• [34]Fowler CD, Arends MA, Kenny PJ: Subtypes of nicotinic acetylcholine receptors in nicotine reward, dependence, and withdrawal: evidence from genetically modified mice. Behav Pharmacol 2008, 19(5–6):461.
• [35]Guan ZZ, Yu WF, Nordberg A: Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Neurochem Int 2003, 43(3):243-249.
• [36]Yang CS, Chen WY, Tsai PJ, Cheng FC, Kuo JS: Effect of diethylmaleate on liver extracellular glutathione levels before and after global liver ischemia in anesthetized rats. Biochem Pharmacol 1997, 53(3):357-361.
• [37]Robillard JM, Gordon GR, Choi HB, Christie BR, MacVicar BA: Glutathione Restores the Mechanism of Synaptic Plasticity in Aged Mice to That of the Adult. PloS one 2011, 6(5):e20676.
• [38]Pears MR, Cooper JD, Mitchison HM, Mortishire-Smith RJ, Pearce DA, Griffin JL: High resolution 1H NMR-based metabolomics indicates a neurotransmitter cycling deficit in cerebral tissue from a mouse model of Batten disease. J Biol Chem 2005, 280(52):42508-42514.
• [39]Zhang X, Liu H, Wu J, Liu M, Wang Y: Metabonomic alterations in hippocampus, temporal and prefrontal cortex with age in rats. Neurochem Int 2009, 54(8):481-487.
• [40]Shao X, Hu Z, Hu C, Bu Q, Yan G, Deng P, Lv L, Wu D, Deng Y, Zhao J: Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism. Toxicol and applied Pharmacol 2012, 260(3):260-270.
• [41]Oudit GY, Trivieri MG, Khaper N, Husain T, Wilson GJ, Liu P, Sole MJ, Backx PH: Taurine supplementation reduces oxidative stress and improves cardiovascular function in an iron-overload murine model. Circulation 2004, 109(15):1877-1885.
• [42]Lan M, McLoughlin G, Griffin J, Tsang T, Huang J, Yuan P, Manji H, Holmes E, Bahn S: Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder. Mol Psychiatry 2008, 14(3):269-279.
• [43]Paschen W, Van Den Kerckhoff W, Hossmann KA: Glycerol as an indicator of lipid degradation in bicuculline-induced seizures and experimental cerebral ischemia. Metab brain Dis 1986, 1(1):37-44.
• [44]Khan AR, Rana P, Devi MM, Chaturvedi S, Javed S, Tripathi RP, Khushu S: Nuclear magnetic resonance spectroscopy-based metabonomic investigation of biochemical effects in serum of γ-irradiated mice. Int J of Radiat Biol 2010, 00:1-7.
• [45]Chakraborty G, Mekala P, Yahya D, Wu G, Ledeen RW: Intraneuronal N-acetylaspartate supplies acetyl groups for myelin lipid synthesis: evidence for myelin-associated aspartoacylase. J of Neurochem 2001, 78(4):736-745.
• [46]Demougeot C, Marie C, Giroud M, Beley A: N‒Acetylaspartate: a literature review of animal research on brain ischaemia. J of Neurochem 2004, 90(4):776-783.
• [47]Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M: The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003, 112(2):257-269.
• [48]Lu B: Pro-region of neurotrophins: role in synaptic modulation. Neuron 2003, 39(5):735-738.
• [49]Levin BE: Metabolic sensors: viewing glucosensing neurons from a broader perspective. Physiol & Behav 2002, 76(3):397-401.
• [50]Ivanov A, Zilberter Y: Critical state of energy metabolism in brain slices: the principal role of oxygen delivery and energy substrates in shaping neuronal activity. Front Neuroenerg 2011, 3:1-9.
• [51]Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Poljak A, Grant R: Age related changes in NAD+ metabolism oxidative stress and sirt1 activity in wistar rats. PloS one 2011, 6(4):e19194.
• [52]Wilhelm F, Hirrlinger J: The NAD+ /NADH redox state in astrocytes: independent control of the NAD+ and NADH content. J Neurosci Res 2011, 89(12):1956-1964.
• [53]Debora E, Lila O, Allain B, Carlos H, Gabriel S, Eliane R, Caio M, do Nascimento Claudia O: A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats. Lipids Health Dis 2011, 16:18-20.
• [54]Mayer J, Thomas DW: Regulation of food intake and obesity. Science 1967, 156(3773):328-337.
• [55]Ritter RC, Slusser PG, Stone S: Glucoreceptors controlling feeding and blood glucose: location in the hindbrain. Science 1981, 213(4506):451-452.
• [56]Buccafusco J, Jackson W, Terry A, Marsh K, Decker M, Arneric S: Improvement in performance of a delayed matching-to-sample task by monkeys following ABT-418: a novel cholinergic channel activator for memory enhancement. Psychopharmacology 1995, 120(3):256-266.
• [57]Levin ED, Chen E: Nicotinic involvement in memory function in zebrafish. Neurotoxicol and Teratol 2004, 26(6):731-735.
• [58]Halestrap AP, Price NT: The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 1999, 343(Pt 2):281.
• [59]Morris AAM: Cerebral ketone body metabolism. J of Inherited Metab Dis 2005, 28(2):109-121.
• [60]Cheng S, Chen GQ, Leski M, Zou B, Wang Y, Wu Q: The effect of D, L-β-hydroxybutyric acid on cell death and proliferation in L929 cells. Biomaterials 2006, 27(20):3758-3765.
• [61]Bontempi B, Laurent-Demir C, Destrade C, Jaffard R: Time-dependent reorganization of brain circuitry underlying long-term memory storage. Nature 1999, 400(6745):671-675.
• [62]Thiagarajan TC, Lindskog M, Tsien RW: Adaptation to synaptic inactivity in hippocampal neurons. Neuron 2005, 47(5):725-737.
• [63]Macallan D, McNurlan M, Kurpad A, De Souza G, Shetty P, Calder A, Griffin G: Whole body protein metabolism in human pulmonary tuberculosis and undernutrition: evidence for anabolic block in tuberculosis. Clin Sci 1998, 94(3):321-331.
• [64]Levin L, Gevers W, Jardine L, De Guel F, Duncan E: Serum amino acids in weight-losing patients with cancer and tuberculosis. Eur J of Cancer and Clin Oncol 1983, 19(6):711-715.
• [65]Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 2009, 457(7231):910-914.