Advertisement

Regional Metabolic Patterns of Abnormal Postoperative Behavioral Performance in Aged Mice Assessed by 1H-NMR Dynamic Mapping Method

  • Taotao Liu
  • Zhengqian Li
  • Jindan He
  • Ning Yang
  • Dengyang Han
  • Yue Li
  • Xuebi Tian
  • Huili Liu
  • Anne Manyande
  • Hongbing Xiang
  • Fuqiang Xu
  • Jie WangEmail author
  • Xiangyang GuoEmail author
Original Article

Abstract

Abnormal postoperative neurobehavioral performance (APNP) is a common phenomenon in the early postoperative period. The disturbed homeostatic status of metabolites in the brain after anesthesia and surgery might make a significant contribution to APNP. The dynamic changes of metabolites in different brain regions after anesthesia and surgery, as well as their potential association with APNP are still not well understood. Here, we used a battery of behavioral tests to assess the effects of laparotomy under isoflurane anesthesia in aged mice, and investigated the metabolites in 12 different sub-regions of the brain at different time points using proton nuclear magnetic resonance (1H-NMR) spectroscopy. The abnormal neurobehavioral performance occurred at 6 h and/or 9 h, and recovered at 24 h after anesthesia/surgery. Compared with the control group, the altered metabolite of the model group at 6 h was aspartate (Asp), and the difference was mainly displayed in the cortex; while significant changes at 9 h occurred predominantly in the cortex and hippocampus, and the corresponding metabolites were Asp and glutamate (Glu). All changes returned to baseline at 24 h. The altered metabolic changes could have occurred as a result of the acute APNP, and the metabolites Asp and Glu in the cortex and hippocampus could provide preliminary evidence for understanding the APNP process.

Keywords

Abnormal postoperative neurobehavioral performance 1H-NMR Metabolite Aspartate Glutamate 

Notes

Acknowledgements

We would like to express our gratitude to Mrs. Pingping An (Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences) for her help in housing the animals. This work was supported by grants from the National Natural Science Foundation of China (8187051484, 8157050329, and 81600933), the Interdisciplinary Medicine Seed Fund of Peking University (BMU2017MC006), and the Youth Innovation Promotion Association of the Chinese Academy of Sciences, China (Y6Y0021004).

Conflict of interest

The authors declare no competing financial interests.

Supplementary material

12264_2019_414_MOESM1_ESM.pdf (649 kb)
Supplementary material 1 (PDF 648 kb)

References

  1. 1.
    Pinho C, Cruz S, Santos A, Abelha FJ. Postoperative delirium: age and low functional reserve as independent risk factors. J Clin Anesth 2016, 33: 507–513.CrossRefGoogle Scholar
  2. 2.
    Pendlebury ST, Lovett NG, Smith SC, Dutta N, Bendon C, Lloyd-Lavery A, et al. Observational, longitudinal study of delirium in consecutive unselected acute medical admissions: age-specific rates and associated factors, mortality and re-admission. BMJ Open 2015, 5: e007808.CrossRefGoogle Scholar
  3. 3.
    Allaili N, Valabregue R, Auerbach EJ, Guillemot V, Yahia-Cherif L, Bardinet E, et al. Single-voxel H-1 spectroscopy in the human hippocampus at 3 T using the LASER sequence: characterization of neurochemical profile and reproducibility. NMR Biomed 2015, 28: 1209–1217.CrossRefGoogle Scholar
  4. 4.
    Cui B, Wu MG, She XJ, Liu HT. Impulse noise exposure in rats causes cognitive deficits and changes in hippocampal neurotransmitter signaling and tau phosphorylation. Brain Res 2012, 1427: 35–43.CrossRefGoogle Scholar
  5. 5.
    Liu TT, He ZG, Tian XB, Kamal GM, Li ZX, Liu ZY, et al. Specific patterns of spinal metabolites underlying alpha-Me-5-HT-evoked pruritus compared with histamine and capsaicin assessed by proton nuclear magnetic resonance spectroscopy. Biochim Biophys Acta-Mol Basis Dis 2017, 1863: 1222–1230.CrossRefGoogle Scholar
  6. 6.
    Meyerhoff DJ, MacKay S, Bachman L, Poole N, Dillon WP, Weiner MW, et al. Reduced brain N-acetylaspartate suggests neuronal loss in cognitively impaired human immunodeficiency virus-seropositive individuals: in vivo 1H magnetic resonance spectroscopic imaging. Neurology 1993, 43: 509–515.CrossRefGoogle Scholar
  7. 7.
    Andres RH, Ducray AD, Schlattner U, Wallimann T, Widmer HR. Functions and effects of creatine in the central nervous system. Brain Res Bull 2008, 76: 329–343.CrossRefGoogle Scholar
  8. 8.
    Boulanger Y, Labelle M, Khiat A. Role of phospholipase A(2) on the variations of the choline signal intensity observed by 1H magnetic resonance spectroscopy in brain diseases. Brain Res Brain Res Rev 2000, 33: 380–389.CrossRefGoogle Scholar
  9. 9.
    Niciu MJ, Kelmendi B, Sanacora G. Overview of glutamatergic neurotransmission in the nervous system. Pharmacol Biochem Behav 2012, 100: 656–664.CrossRefGoogle Scholar
  10. 10.
    Wang XF, Zhao TY, Su RB, Wu N, Li J. Agmatine prevents adaptation of the hippocampal glutamate system in chronic morphine-treated rats. Neurosci Bull 2016, 32: 523–530.CrossRefGoogle Scholar
  11. 11.
    Maddock RJ, Buonocore MH. MR spectroscopic studies of the brain in psychiatric disorders. Curr Top Behav Neurosci 2012, 11: 199–251.CrossRefGoogle Scholar
  12. 12.
    Shi J, Li Q, Wen T. Dendritic cell factor 1-knockout results in visual deficit through the GABA system in mouse primary visual cortex. Neurosci Bull 2018, 34: 465–475.CrossRefGoogle Scholar
  13. 13.
    Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 2000, 13: 129–153.CrossRefGoogle Scholar
  14. 14.
    Wang J, Du H, Jiang L, Ma X, de Graaf RA, Behar KL, et al. Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure. Proc Natl Acad Sci U S A 2013, 110: 14444–14449.CrossRefGoogle Scholar
  15. 15.
    Gonzalez-Riano C, Garcia A, Barbas C. Metabolomics studies in brain tissue: a review. J Pharm Biomed Anal 2016, 130: 141–168.CrossRefGoogle Scholar
  16. 16.
    Clausen MR, Edelenbos M, Bertram HC. Mapping the variation of the carrot metabolome using H-1 NMR spectroscopy and consensus PCA. J Agric Food Chem 2014, 62: 4392–4398.CrossRefGoogle Scholar
  17. 17.
    Peng JN, Patil SM, Keire DA, Chen K. Chemical structure and composition of major glycans covalently linked to therapeutic monoclonal antibodies by middle-down nuclear magnetic resonance. Anal Chem 2018, 90: 11016–11024.CrossRefGoogle Scholar
  18. 18.
    Peng M, Zhang C, Dong Y, Zhang Y, Nakazawa H, Kaneki M, et al. Battery of behavioral tests in mice to study postoperative delirium. Sci Rep 2016, 6: 29874.CrossRefGoogle Scholar
  19. 19.
    Yang SM, Gu CP, Mandeville ET, Dong YL, Esposito E, Zhang YY, et al. Anesthesia and surgery impair blood-brain barrier and cognitive function in mice. Front Immunol 2017, 8: 902.CrossRefGoogle Scholar
  20. 20.
    Nathan BP, Yost J, Litherland MT, Struble RG, Switzer PV. Olfactory function in apoE knockout mice. Behav Brain Res 2004, 150: 1–7.CrossRefGoogle Scholar
  21. 21.
    Wang J, Zeng HL, Du H, Liu Z, Cheng J, Liu T, et al. Evaluation of metabolites extraction strategies for identifying different brain regions and their relationship with alcohol preference and gender difference using NMR metabolomics. Talanta 2018, 179: 369–376.CrossRefGoogle Scholar
  22. 22.
    Wang J, Du H, Ma X, Pittman B, Castracane L, Li TK, et al. Metabolic products of [2-(13) C]ethanol in the rat brain after chronic ethanol exposure. J Neurochem 2013, 127: 353–364.CrossRefGoogle Scholar
  23. 23.
    Du H, Fu J, Wang S, Liu H, Zeng Y, Yang J, et al. 1H-NMR metabolomics analysis of nutritional components from two kinds of freshwater fish brain extracts. RSC Adv 2018, 8: 19470–19478.CrossRefGoogle Scholar
  24. 24.
    Liu ML, Mao XA, Ye CH, Huang H, Nicholson JK, Lindon JC. Improved WATERGATE pulse sequences for solvent suppression in NMR spectroscopy. J Magn Reson 1998, 132: 125–129.CrossRefGoogle Scholar
  25. 25.
    Liu Y, Cheng J, Liu HL, Deng YH, Wang J, Xu FQ. NMRSpec: an integrated software package for processing and analyzing one dimensional nuclear magnetic resonance spectra. Chemom Intell Lab Syst 2017, 162: 142–148.CrossRefGoogle Scholar
  26. 26.
    Kamal GM, Wang XH, Yuan B, Wang J, Sun P, Zhang X, et al. Compositional differences among Chinese soy sauce types studied by C-13 NMR spectroscopy coupled with multivariate statistical analysis. Talanta 2016, 158: 89–99.CrossRefGoogle Scholar
  27. 27.
    Kamal GM, Yuan B, Hussain AI, Wang J, Jiang B, Zhang X, et al. C-13-NMR-based metabolomic profiling of typical Asian soy sauces. Molecules 2016, 21: 1168.CrossRefGoogle Scholar
  28. 28.
    Zhang LM, Wang LM, Hu YL, Liu ZG, Tian Y, Wu XC, et al. Selective metabolic effects of gold nanorods on normal and cancer cells and their application in anticancer drug screening. Biomaterials 2013, 34: 7117–7126.CrossRefGoogle Scholar
  29. 29.
    Lehmkuhl AM, Dirr ER, Fleming SM. Olfactory assays for mouse models of neurodegenerative disease. J Vis Exp 2014, 90: e51804.Google Scholar
  30. 30.
    Maldonado JR. Delirium pathophysiology: an updated hypothesis of the etiology of acute brain failure. Int J Geriatr Psychiatry 2017, 33: 1428–1457.CrossRefGoogle Scholar
  31. 31.
    Frank LM, Brown EN, Wilson M. Trajectory encoding in the hippocampus and entorhinal cortex. Neuron 2000, 27: 169–178.CrossRefGoogle Scholar
  32. 32.
    Bannerman DM, Rawlins JNP, McHugh SB, Deacon RMJ, Yee BK, Bast T, et al. Regional dissociations within the hippocampus—memory and anxiety. Neurosci Biobehav Rev 2004, 28: 273–283.CrossRefGoogle Scholar
  33. 33.
    Chang RYK, Nouwens AS, Dodd PR, Etheridge N. The synaptic proteome in Alzheimer’s disease. Alzheimers Dement 2013, 9: 499–511.CrossRefGoogle Scholar
  34. 34.
    Kang MG, Byun K, Kim JH, Park NH, Heinsen H, Ravid R, et al. Proteogenomics of the human hippocampus: the road ahead. BBA-Proteins Proteom 2015, 1854: 788–797.CrossRefGoogle Scholar
  35. 35.
    Focking M, Lopez LM, English JA, Dicker P, Wolff A, Brindley E, et al. Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia. Mol Psychiatr 2015, 20: 424–432.CrossRefGoogle Scholar
  36. 36.
    Fong TG, Bogardus ST, Daftary A, Auerbach E, Blumenfeld H, Modur S, et al. Cerebral perfusion changes in older delirious patients using 99mTc HMPAO SPECT. J Gerontol A-Biol Sci Med Sci 2006, 61: 1294–1299.CrossRefGoogle Scholar
  37. 37.
    Yokota H, Ogawa S, Kurokawa A, Yamamoto Y. Regional cerebral blood flow in delirium patients. Psychiatr Clin Neurosci 2003, 57: 337–339.CrossRefGoogle Scholar
  38. 38.
    Cavallari M, Dai WY, Guttmann CRG, Meier DS, Ngo LH, Hshieh TT, et al. Neural substrates of vulnerability to postsurgical delirium as revealed by presurgical diffusion MRI. Brain 2016, 139: 1282–1294.CrossRefGoogle Scholar
  39. 39.
    Choi SH, Lee H, Chung TS, Park KM, Jung YC, Kim SI, et al. Neural network functional connectivity during and after an episode of delirium. Am J Psychiatry 2012, 169: 498–507.CrossRefGoogle Scholar
  40. 40.
    D’Aniello G, Tolino A, D’Aniello A, Errico F, Fisher GH, Di Fiore MM. The role of D-aspartic acid and N-methyl-D-aspartic acid in the regulation of prolactin release. Endocrinology 2000, 141: 3862–3870.CrossRefGoogle Scholar
  41. 41.
    D’Aniello S, Somorjai I, Garcia-Fernandez J, Topo E, D’Aniello A. D-aspartic acid is a novel endogenous neurotransmitter. FASEB J 2011, 25: 1014–1027.CrossRefGoogle Scholar
  42. 42.
    Palazzo E, Luongo L, Guida F, Marabese I, Romano R, Iannotta M, et al. D-aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice. Amino Acids 2016, 48: 1553–1567.CrossRefGoogle Scholar
  43. 43.
    Errico F, Nistico R, Napolitano F, Mazzola C, Astone D, Pisapia T, et al. Increased D-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice. Neurobiol Aging 2011, 32: 2229–2243.CrossRefGoogle Scholar
  44. 44.
    Dunlop DS, Neidle A, Mchale D, Dunlop DM, Lajtha A. The presence of free D-aspartic acid in rodents and man. Biochem Biophys Res Commun 1986, 141: 27–32.CrossRefGoogle Scholar
  45. 45.
    Errico F, Nistico R, Napolitano F, Oliva AB, Romano R, Barbieri F, et al. Persistent increase of D-aspartate in D-aspartate oxidase mutant mice induces a precocious hippocampal age-dependent synaptic plasticity and spatial memory decay. Neurobiol Aging 2011, 32: 2061–2074.CrossRefGoogle Scholar
  46. 46.
    Benarroch EE. Glutamate transporters diversity, function, and involvement in neurologic disease. Neurology 2010, 74: 259–264.CrossRefGoogle Scholar
  47. 47.
    Kroll JL, Steele AM, Pinkham AE, Choi C, Khan DA, Patel SV, et al. Hippocampal metabolites in asthma and their implications for cognitive function. Neuroimage Clin 2018, 19: 213–221.CrossRefGoogle Scholar
  48. 48.
    Boretius S, Tammer R, Michaelis T, Brockmoller J, Frahm J. Halogenated volatile anesthetics alter brain metabolism as revealed by proton magnetic resonance spectroscopy of mice in vivo. Neuroimage 2013, 69: 244–255.CrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  • Taotao Liu
    • 1
    • 2
  • Zhengqian Li
    • 1
  • Jindan He
    • 1
  • Ning Yang
    • 1
  • Dengyang Han
    • 1
  • Yue Li
    • 1
  • Xuebi Tian
    • 3
  • Huili Liu
    • 2
  • Anne Manyande
    • 4
  • Hongbing Xiang
    • 3
  • Fuqiang Xu
    • 2
    • 5
  • Jie Wang
    • 2
    • 5
    • 6
    Email author
  • Xiangyang Guo
    • 1
    Email author
  1. 1.Department of AnesthesiologyPeking University Third HospitalBeijingChina
  2. 2.Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and MathematicsChinese Academy of SciencesWuhanChina
  3. 3.Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  4. 4.School of Human and Social SciencesUniversity of West LondonMiddlesexUK
  5. 5.University of Chinese Academy of SciencesBeijingChina
  6. 6.The Second Hospital of ShijiazhuangShijiazhuangChina

Personalised recommendations