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Studies on the Neuromodulatory Effects of Ginkgo biloba on Alterations in Lipid Composition and Membrane Integrity of Rat Brain Following Aluminium Neurotoxicity

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Abstract

Brain contains the highest lipid content involved in various structural and physiological activities such as structural development, neurogenesis, synaptogenesis, signal transduction and myelin sheath formation. Lipids bilayer is essential to maintain the structural integrity for the physiological functions of protein. Impairments in lipid metabolism and its composition can lead to the progression of various brain ailments such as neurodegenerative and neuropsychiatric disorders. Aluminium (Al), the potent neurotoxin has been linked to Alzheimer’s disease (AD) like pathology. Al can bind to biomembrane and influence oligomerization and conformational changes of proteins by acting as cross-linkers. The present study evaluated the influence of Ginkgo biloba (GBE) on the lipid profile alterations induced by Al lactate in hippocampal and cortical regions using FTIR spectroscopy. Rats were exposed with 10 mg/kg b.w. (intraperitoneal) of Al lactate for 6 weeks. This was followed by a treatment protocol of GBE (100 mg/kg b.w.) both preexposure (2 weeks) and conjunctive (6 weeks) exposure. A self recovery group was also included, where Al withdrawal was done for 2 weeks post Al exposure. A significant decrease in peak areas of cholesterol, sphingolipids and phospholipids was observed in Al treated groups. Further, polyunsaturated fatty acids and membrane fluidity has also decreased, as revealed by olefinic and methyl asymmetric stretching bands. Al treatment significantly increased the fluorescence polarization, anisotropy and order parameter, which however were normalized following GBE supplementation. Results also showed that pretreatment with GBE provided more beneficial effects on the adverse changes following Al in membrane composition and behavioral outcome.

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Abbreviations

Al:

Aluminium

Aβ:

Amyloid beta

BBB:

Blood Brain Barrier

BSA:

Bovine serum albumin

Fig:

Figure

i.p:

Intra-peritoneal

LPO:

Lipid peroxidation

MDA:

Malondialdehyde

kg:

Kilogram

mg:

Milligram

Tris HCl:

Tris Hydrochloride

TBA:

Thiobarbituric acid

TBARS:

Thiobarbituric Acid Reactive Substances

TCA:

Tricholro acetic acid

GBE:

Ginkgo biloba Extract

References

  1. Cermenati G, Mitro N, Audano M, Melcangi RC, Crestani M, De Fabiani E, Caruso D (2015) Lipids in the nervous system: from biochemistry and molecular biology to patho-physiology. Biochim Biophys Acta 1851(1):51–60

    CAS  PubMed  Google Scholar 

  2. Schmitt F, Hussain G, Dupuis L, Loeffler JP, Henriques A (2014) A plural role for lipids in motor neuron diseases: energy, signaling and structure. Front Cell Neurosci 8:25

    PubMed  PubMed Central  Google Scholar 

  3. Hussain G, Anwar H, Rasul A, Imran A, Qasim M, Zafar S et al (2020) Lipids as biomarkers of brain disorders. Crit Rev Food Sci Nutr 60(3):351–374

    CAS  PubMed  Google Scholar 

  4. Dreissig I, Machill S, Salzer R, Krafft C (2009) Quantification of brain lipids by FTIR spectroscopy and partial least squares regression. Spectrochim Acta Part A 71(5):2069–2075

    Google Scholar 

  5. Aureli M, Grassi S, Prioni S, Sonnino S, Prinetti A (2015) Lipid membrane domains in the brain. Biochim Biophys Acta 1851(8):1006–1016

    CAS  PubMed  Google Scholar 

  6. Olsen AS, Færgeman NJ (2017) Sphingolipids: membrane microdomains in brain development, function and neurological diseases. Open Biol 7(5):170069

    PubMed  PubMed Central  Google Scholar 

  7. Brown HA, Murphy RC (2009) Working towards an exegesis for lipids in biology. Nat Chem Biol 5(9):602–606

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Bozek K, Wei Y, Yan Z, Liu X, Xiong J, Sugimoto M et al (2015) Organization and evolution of brain lipidome revealed by large-scale analysis of human, chimpanzee, macaque, and mouse tissues. Neuron 85(4):695–702

    CAS  PubMed  Google Scholar 

  9. Müller CP, Reichel M, Mühle C, Rhein C, Gulbins E, Kornhuber J (2015) Brain membrane lipids in major depression and anxiety disorders. Biochim Biophys Acta 1851(8):1052–1065

    PubMed  Google Scholar 

  10. Lingwood D, Simons K (2010) Lipid rafts as a membrane-organizing principle. Science 327(5961):46–50

    CAS  PubMed  Google Scholar 

  11. Vetrivel KS, Meckler X, Chen Y, Nguyen PD, Seidah NG, Vassar R et al (2009) Alzheimer disease Aβ production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid rafts. J Biol Chem 284(6):3793–3803

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Parsons RB, Austen BM (2007) Protein–protein interactions in the assembly and subcellular trafficking of the BACE (β-site amyloid precursor protein-cleaving enzyme) complex of Alzheimer's disease

  13. Marin R, Fabelo N, Fernández-Echevarría C, Canerina-Amaro A, Rodríguez-Barreto D, Quinto-Alemany D et al (2016) Lipid raft alterations in aged-associated neuropathologies. Curr Alzheimer Res 13(9):973–984

    CAS  PubMed  Google Scholar 

  14. Marin R, Diaz M (2018) Estrogen interactions with lipid rafts related to neuroprotection. Impact of brain ageing and menopause. Front Neurosci 12:128

    PubMed  PubMed Central  Google Scholar 

  15. Verma S, Sharma S, Ranawat P, Nehru B (2020) Modulatory effects of Ginkgo biloba against amyloid aggregation through induction of heat shock proteins in aluminium induced neurotoxicity. Neurochem Res 45:465

    CAS  PubMed  Google Scholar 

  16. Pandya JD, Dave KR, Katyare SS (2004) Effect of long-term aluminum feeding on lipid/phospholipid profiles of rat brain myelin. Lipids Health Dis 3(1):13

    PubMed  PubMed Central  Google Scholar 

  17. Bhalla P, Nair P, Garg ML, Dhawan DK (2009) Effects of lithium on membrane fluidity and lipid profile in brain membranes of aluminum-treated rats. Toxicol Environ Chem 91(4):723–733

    CAS  Google Scholar 

  18. Kneipp J, Lasch P, Baldauf E, Beekes M, Naumann D (2000) Detection of pathological molecular alterations in scrapie-infected hamster brain by Fourier transform infrared (FT-IR) spectroscopy. Biochim Biophys Acta 1501(2–3):189–199

    CAS  PubMed  Google Scholar 

  19. Çakmak G, Togan I, Uğuz C, Severcan F (2003) FT-IR spectroscopic analysis of rainbow trout liver exposed to nonylphenol. Appl Spectrosc 57(7):835–841

    PubMed  Google Scholar 

  20. Mourant JR, Yamada YR, Carpenter S, Dominique LR, Freyer JP (2003) FTIR spectroscopy demonstrates biochemical differences in mammalian cell cultures at different growth stages. Biophys J 85(3):1938–1947

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Severcan F, Toyran N, Kaptan N, Turan B (2000) Fourier transform infrared study of the effect of diabetes on rat liver and heart tissues in the C–H region. Talanta 53(1):55–59

    CAS  PubMed  Google Scholar 

  22. Verma S, Ranawat P, Sharma N, Nehru B (2019) Ginkgo biloba attenuates aluminum lactate-induced neurotoxicity in reproductive senescent female rats: behavioral, biochemical, and histopathological study. Environ Sci Pollut Res 26(26):27148–27167

    CAS  Google Scholar 

  23. Ali T, Yoon GH, Shah SA, Lee HY, Kim MO (2015) Osmotin attenuates amyloid beta-induced memory impairment, tau phosphorylation and neurodegeneration in the mouse hippocampus. Sci Rep 5(1):1–17

    CAS  Google Scholar 

  24. Itoh J, Nabeshima T, Kameyama T (1991) Utility of an elevated plus-maze for dissociation of amnesic and behavioral effects of drugs in mice. Eur J Pharmacol 194(1):71–76

    CAS  PubMed  Google Scholar 

  25. Nehru B, Verma R, Khanna P, Sharma SK (2008) Behavioral alterations in rotenone model of Parkinson's disease: attenuation by co-treatment of centrophenoxine. Brain Res 1201:122–127

    CAS  PubMed  Google Scholar 

  26. Kulkarni SK (1999) Handbook of experimental pharmacology, 3rdrd rev edn. Vallabh Prakashan, New Delhi, pp 123–125

    Google Scholar 

  27. Kalonia H, Mishra J, Kumar A (2012) Targeting neuro-inflammatory cytokines and oxidative stress by minocycline attenuates quinolinic-acid-induced Huntington’s disease-like symptoms in rats. Neurotox Res 22(4):310–320

    CAS  PubMed  Google Scholar 

  28. Sivakumar S, Sivasubramanian J, Raja B (2012) Aluminium induced structural, metabolic alterations and protective effects of desferrioxamine in the brain tissue of mice: an FTIR study. Spectrochim Acta Part A 99:252–258

    CAS  Google Scholar 

  29. Sivakumar S, Khatiwada CP, Sivasubramanian J, Raja B (2014) Protective effects of deferiprone and desferrioxamine in brain tissue of aluminum intoxicated mice: an FTIR study. Biomed Prev Nutr 4(1):53–61

    Google Scholar 

  30. Trush MA, Mimnaugh EG, Ginsburg E, Gram TE (1981) In vitro stimulation by paraquat of reactive oxygen-mediated lipid peroxidation in rat lung microsomes. Toxicol Appl Pharmacol 60(2):279–286

    CAS  PubMed  Google Scholar 

  31. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  32. Pearse AGE (1968) Histochemistry, theoretical and applied: theoretical and applied. Churchill Livingstone, London

    Google Scholar 

  33. Humanson GL (1961) Basic procedures-animal tissue technique. Part I. WH Freeman and Company, San Francisco, pp 130–132

    Google Scholar 

  34. Lin SCC, Way EL (1982) A high affinity Ca2+-ATPase in enriched nerve-ending plasma membranes. Brain Res 235(2):387–392

    CAS  PubMed  Google Scholar 

  35. Lin SCC, Way EL (1984) Characterization of calcium-activated and magnesium-activated ATPases of brain nerve endings. J Neurochem 42(6):1697–1706

    CAS  PubMed  Google Scholar 

  36. Swapna I, Kumar KSS, Murthy CR, Senthilkumaran B (2006) Membrane alterations and fluidity changes in cerebral cortex during acute ammonia intoxication. Neurotoxicology 27(3):402–408

    CAS  PubMed  Google Scholar 

  37. Shinitzky M, Barenholz Y (1974) Dynamics of the hydrocarbon layer in liposomes of lecithin and sphingomyelin containing dicetylphosphate. J Biol Chem 249(8):2652–2657

    CAS  PubMed  Google Scholar 

  38. Pottel H, van der Meer W, Herreman W (1983) Correlation between the order parameter and the steady-state fluorescence anisotropy of 1, 6-diphenyl-1, 3, 5-hexatriene and an evaluation of membrane fluidity. Biochim Biophys Acta 730(2):181–186

    CAS  Google Scholar 

  39. Massey V, Williams CH (1965) On the reaction mechanism of yeast glutathione reductase. J Biol Chem 240(11):4470–4480

    CAS  PubMed  Google Scholar 

  40. Vanderkooi JM, Callis JB (1974) Pyrene. Probe of lateral diffusion in the hydrophobic region of membranes. Biochemistry 13(19):4000–4006

    CAS  PubMed  Google Scholar 

  41. Akkas SB, Inci S, Zorlu F, Severcan F (2007) Melatonin affects the order, dynamics and hydration of brain membrane lipids. J Mol Struct 834:207–215

    Google Scholar 

  42. Liu KZ, Bose R, Mantsch HH (2002) Infrared spectroscopic study of diabetic platelets. Vib Spectrosc 28(1):131–136

    CAS  Google Scholar 

  43. Sharma AC, Kulkarni SK (1992) Evaluation of learning and memory mechanisms employing elevated plus-maze in rats and mice. Prog Neuropsychopharmacol Biol Psychiatry 16(1):117–125

    CAS  PubMed  Google Scholar 

  44. Shiotsuki H, Yoshimi K, Shimo Y, Funayama M, Takamatsu Y, Ikeda K et al (2010) A rotarod test for evaluation of motor skill learning. J Neurosci Methods 189(2):180–185

    PubMed  Google Scholar 

  45. Sumathi T, Shobana C, Kumari BR, Nandhini DN (2011) Protective role of Cynodon dactylon in ameliorating the aluminium-induced neurotoxicity in rat brain regions. Biol Trace Elem Res 144(1–3):843–853

    CAS  PubMed  Google Scholar 

  46. Pogue AI, Lukiw WJ (2016) Aluminum, the genetic apparatus of the human CNS and Alzheimer's disease (AD). Morphologie 100(329):56–64

    CAS  PubMed  Google Scholar 

  47. Lukiw WJ (2013) Alzheimer's disease (AD) as a disorder of the plasma membrane. Front Physiol 4:24

    PubMed  PubMed Central  Google Scholar 

  48. Mesa-Herrera F, Taoro-González L, Valdés-Baizabal C, Diaz M, Marín R (2019) Lipid and lipid raft alteration in aging and neurodegenerative diseases: a window for the development of new biomarkers. Int J Mol Sci 20(15):3810

    PubMed Central  Google Scholar 

  49. Sood PK, Verma S, Nahar U, Nehru B (2015) Neuroprotective role of lazaroids against aluminium chloride poisoning. Neurochem Res 40(8):1699–1708

    CAS  PubMed  Google Scholar 

  50. Lee HJ, Korshavn KJ, Kochi A, Derrick JS, Lim MH (2014) Cholesterol and metal ions in Alzheimer's disease. Chem Soc Rev 43(19):6672–6682

    CAS  PubMed  Google Scholar 

  51. Petrov AM, Kasimov MR, Zefirov AL (2016) Brain cholesterol metabolism and its defects: linkage to neurodegenerative diseases and synaptic dysfunction. Acta Naturae 8(1):58–73

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Sood PK, Nahar U, Nehru B (2011) Curcumin attenuates aluminum-induced oxidative stress and mitochondrial dysfunction in rat brain. Neurotox Res 20(4):351

    CAS  PubMed  Google Scholar 

  53. Marcheggiani F, Cirilli I, Orlando P, Silvestri S, Vogelsang A, Knott A, Blatt T, Weise JM, Tiano L (2019) Modulation of Coenzyme Q10 content and oxidative status in human dermal fibroblasts using HMG-CoA reductase inhibitor over a broad range of concentrations. From mitohormesis to mitochondrial dysfunction and accelerated aging. Aging (Albany NY) 11(9):2565

    CAS  Google Scholar 

  54. Cakmak G, Zorlu F, Severcan M, Severcan F (2011) Screening of protective effect of amifostine on radiation-induced structural and functional variations in rat liver microsomal membranes by FT-IR spectroscopy. Anal Chem 83(7):2438–2444

    CAS  PubMed  Google Scholar 

  55. Garip S, Bozoglu F, Severcan F (2007) Differentiation of mesophilic and thermophilic bacteria with Fourier transform infrared spectroscopy. Appl Spectrosc 61(2):186–192

    CAS  PubMed  Google Scholar 

  56. Swegert CV, Dave KR, Katyare SS (1999) Effect of aluminium-induced Alzheimer like condition on oxidative energy metabolism in rat liver, brain and heart mitochondria. Mech Ageing Dev 112(1):27–42

    CAS  PubMed  Google Scholar 

  57. Verstraeten SV, Oteiza PI (2000) Effects of Al3+ and related metals on membrane phase state and hydration: correlation with lipid oxidation. Arch Biochem Biophys 375(2):340–346

    CAS  PubMed  Google Scholar 

  58. Verstraeten SV, Oteiza PI (2002) Al3+-mediated changes in membrane physical properties participate in the inhibition of polyphosphoinositide hydrolysis. Arch Biochem Biophys 408(2):263–271

    CAS  PubMed  Google Scholar 

  59. Mulder C, Wahlund LO, Teerlink T, Blomberg M, Veerhuis R, Van Kamp GJ et al (2003) Decreased lysophosphatidylcholine/phosphatidylcholine ratio in cerebrospinal fluid in Alzheimer’s disease. J Neural Transm 110(8):949–955

    CAS  PubMed  Google Scholar 

  60. Zamir O, Charlton MP (2006) Cholesterol and synaptic transmitter release at crayfish neuromuscular junctions. J Physiol 571(1):83–99

    CAS  PubMed  Google Scholar 

  61. Ugalde CL, Finkelstein DI, Lawson VA, Hill AF (2016) Pathogenic mechanisms of prion protein, amyloid-β and α-synuclein misfolding: the prion concept and neurotoxicity of protein oligomers. J Neurochem 139(2):162–180

    CAS  PubMed  Google Scholar 

  62. Smith JV, Luo Y (2004) Studies on molecular mechanisms of Ginkgo biloba extract. Appl Microbiol Biotechnol 64(4):465–472

    CAS  PubMed  Google Scholar 

  63. Toyran N, Zorlu F, Dönmez G, Öğe K, Severcan F (2004) Chronic hypoperfusion alters the content and structure of proteins and lipids of rat brain homogenates: a Fourier transform infrared spectroscopy study. Eur Biophys J 33(6):549–554

    CAS  PubMed  Google Scholar 

  64. Diaz M, Fabelo N, Martín V, Ferrer I, Gomez T, Marin R (2015) Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/AβPP interaction in early stages of Alzheimer's disease. J Alzheimer's Dis 43(4):1185–1198

    CAS  Google Scholar 

  65. Marin R, Fabelo N, Martín V, Garcia-Esparcia P, Ferrer I, Quinto-Alemany D, Díaz M (2017) Anomalies occurring in lipid profiles and protein distribution in frontal cortex lipid rafts in dementia with Lewy bodies disclose neurochemical traits partially shared by Alzheimer's and Parkinson's diseases. Neurobiol Aging 49:52–59

    CAS  PubMed  Google Scholar 

  66. Piccinini M, Scandroglio F, Prioni S, Buccinnà B, Loberto N, Aureli M et al (2010) Deregulated sphingolipid metabolism and membrane organization in neurodegenerative disorders. Mol Neurobiol 41(2–3):314–340

    CAS  PubMed  Google Scholar 

  67. Derenne A, Vandersleyen O, Goormaghtigh E (2014) Lipid quantification method using FTIR spectroscopy applied on cancer cell extracts. Biochim Biophys Acta 1841(8):1200–1209

    CAS  PubMed  Google Scholar 

  68. Ribes D, Colomina MT, Vicens P, Domingo JL (2010) Impaired spatial learning and unaltered neurogenesis in a transgenic model of Alzheimer's disease after oral aluminum exposure. Curr Alzheimer Res 7(5):401–408

    CAS  PubMed  Google Scholar 

  69. Kaur A, Joshi K, Minz RW, Gill KD (2006) Neurofilament phosphorylation and disruption: a possible mechanism of chronic aluminium toxicity in Wistar rats. Toxicology 219(1–3):1–10

    CAS  PubMed  Google Scholar 

  70. Hu H, Yang YJ, Li XP, Chen GH (2005) Effect of aluminum chloride on motor activity and species-typical behaviors in mice. Zhonghua lao dong wei sheng zhi ye bing za zhi 23(2):132–135

    PubMed  Google Scholar 

  71. Abd-Elhady RM, Elsheikh AM, Khalifa AE (2013) Anti-amnestic properties of Ginkgo biloba extract on impaired memory function induced by aluminum in rats. Int J Dev Neurosci 31(7):598–607

    CAS  PubMed  Google Scholar 

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Acknowledgements

We wish to thank Prof. Bimla Nehru for her invaluable advice and support in the preparation of this work.

Funding

The study was carried out by the funds received by University grants commission-Basic Scientific research (UGC-BSR) to Ms Sonia Verma and DST-PURSE 2017–18, New Delhi to Department of Biophysics, Panjab University.

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Sonia Verma has carried out all the research work presented in this article. She has analysed all the results. She has written and edited the scientific article. All the coauthors has helped the author with their valuable suggestions in the research work and writing the article.

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Correspondence to Bimla Nehru.

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All the protocols performed were approved by Animal Ethical Committee (IAEC) of Panjab University, Chandigarh, India with approval no. PU/45/99/CPCSEA/IAEC/2018/153. Every effort was made to minimize the number of animals and the distress caused throughout the experiment.

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Verma, S., Ranawat, P. & Nehru, B. Studies on the Neuromodulatory Effects of Ginkgo biloba on Alterations in Lipid Composition and Membrane Integrity of Rat Brain Following Aluminium Neurotoxicity. Neurochem Res 45, 2143–2160 (2020). https://doi.org/10.1007/s11064-020-03075-2

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