Skip to main content

Advertisement

SpringerLink
Log in

Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Studies demonstrated that the iron chelating antioxidant restores brain dysfunction induced by iron toxicity in animals. Earlier, we found that iron overload-induced cerebral cortex apoptosis correlated with oxidative stress could be protected by naringenin (NGEN). In this respect, the present study is focused on the mechanisms associated with the protective efficacy of NGEN, natural flavonoid compound abundant in the peels of citrus fruit, on iron induced impairment of the anxiogenic-like behaviour, purinergic and cholinergic dysfunctions with oxidative stress related disorders on mitochondrial function in the rat hippocampus. Results showed that administration of NGEN (50 mg/kg/day) by gavage significantly ameliorated anxiogenic-like behaviour impairment induced by the exposure to 50 mg of Fe-dextran/kg/day intraperitoneally for 28 days in rats, decreased iron-induced reactive oxygen species formation and restored the iron-induced decrease of the acetylcholinesterase expression level, mitochondrial membrane potential and mitochondrial complexes activities in the hippocampus of rats. Moreover, NGEN was able to restore the alteration on the activity and expression of ectonucleotidases such as adenosine triphosphate diphosphohydrolase and 5′-nucleotidase, enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. These results may contribute to a better understanding of the neuroprotective role of NGEN, emphasizing the influence of including this flavonoid in the diet for human health, possibly preventing brain injury associated with iron overload.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Anderson GJ, MacLaren GD (2012) Iron physiology and pathophysiology in humans. Humana Press, New York

    Book  Google Scholar 

  2. You LH, Li F, Wang L, Zhao SE, Wang SM, Zhang LL, Zhang LH, Duan XL, Yu P, Chang YZ (2015) Brain iron accumulation exacerbates the pathogenesis of MPTP-induced Parkinson’s disease. Neuroscience 284:234–246

    Article  CAS  PubMed  Google Scholar 

  3. Lin AM, Ping YH, Chang GF, Wang JY, Chiu JH, Kuo CD, Chi CW (2011) Neuroprotective effect of oral S/B remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) on iron-induced neurodegeneration in the nigrostriatal dopaminergic system of rat brain. J Ethnopharmacol 134(3):884–891

    Article  PubMed  Google Scholar 

  4. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B III, Stockwell BR (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–1072

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Rivera-Mancía S, Pérez-Neri I, Ríos C, Tristán-López L, Rivera-Espinosa L, Montes S (2010) The transition metals copper and iron in neurodegenerative diseases. Chem Biol Interact 186(2):184–199

    Article  PubMed  Google Scholar 

  6. Kim J, Wessling-Resnick M (2014) Iron and mechanisms of emotional behavior. J Nutr Biochem 25(11):1101–1107

    Article  CAS  PubMed  Google Scholar 

  7. Youdim MB (2008) Brain iron deficiency and excess: cognitive impairment and neurodegeneration with involvement of striatum and hippocampus. Neurotox Res 14:45–56

    Article  CAS  PubMed  Google Scholar 

  8. Rodrigue KM, Daugherty AM, Haacke EM, Raz N (2012) The role of hippocampal iron concentration and hippocampal volume in age-related differences in memory. Cereb Cortex 23(7):1533–1541

    Article  PubMed Central  PubMed  Google Scholar 

  9. Park UJ, Lee YA, Won SM, Lee JH, Kang SH, Springer JE, Lee YB, Gwag BJ (2011) Blood-derived iron mediates free radical production and neuronal death in the hippocampal CA1 area following transient forebrain ischemia in rat. Acta Neuropathol 121(4):459–473

    Article  CAS  PubMed  Google Scholar 

  10. Salvador GA, Uranga RM, Giusto NM (2011) Iron and mechanisms of neurotoxicity. Int J Alzheimers Dis. doi:10.4061/2011/720658

    PubMed Central  Google Scholar 

  11. Bostanci MÖ, Bagirici F (2013) Blocking of L-type calcium channels protects hippocampal and nigral neurons against iron neurotoxicity. The role of L-type calcium channels in iron-induced neurotoxicity. Int J Neurosci 123(12):876–882

    Article  CAS  PubMed  Google Scholar 

  12. da Silva VK, de Freitas BS, da Silva Dornelles A, Nery LR, Falavigna L, Ferreira RD, Bogo MR, Hallak JE, Zuardi AW, Crippa JA, Schröder N (2014) Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection. Mol Neurobiol 49(1):222–233

    Article  PubMed  Google Scholar 

  13. Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L (2014) The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol 13(10):1045–1060

    Article  CAS  PubMed  Google Scholar 

  14. Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H (2009) Purinergic signalling in the nervous system: an overview. Trends Neurosci 32:19–29

    Article  CAS  PubMed  Google Scholar 

  15. Masino S, Boison D (2013) Adenosine: a key link between metabolism and brain activity. Springer, New York

    Book  Google Scholar 

  16. Weinreb O, Mandel S, Youdim MB, Amit T (2013) Targeting dysregulation of brain iron homeostasis in Parkinson’s disease by iron chelators. Free Radic Biol Med 62:52–64

    Article  CAS  PubMed  Google Scholar 

  17. Mir IA, Tiku AB (2015) Chemopreventive and therapeutic potential of “naringenin,” a flavanone present in citrus fruits. Nutr Cancer 67(1):27–42

    Article  CAS  PubMed  Google Scholar 

  18. Raza SS, Khan MM, Ahmad A, Ashafaq M, Islam F, Wagner AP, Safhi MM, Islam F (2013) Neuroprotective effect of Naringenin is mediated through suppression of NF-kB signaling pathway in experimental stroke. Neuroscience 230:157–171

    Article  CAS  PubMed  Google Scholar 

  19. Khan MB, Khan MM, Khan A, Ahmed ME, Ishrat T, Tabassum R, Vaibhav K, Ahmad A, Islam F (2012) Naringenin ameliorates Alzheimer’s disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) caused by the intracerebroventricular-streptozotocin in rat model. Neurochem Int 61(7):1081–1093

    Article  CAS  PubMed  Google Scholar 

  20. Chtourou Y, Fetoui H, Gdoura R (2014) Protective effects of naringenin on iron-overload-induced cerebral cortex neurotoxicity correlated with oxidative stress. Biol Trace Elem Res 158(3):376–383

    Article  CAS  PubMed  Google Scholar 

  21. Pandey DK, Yadav SK, Mahesh R, Rajkumar R (2009) Depression-like and anxiety-like behavioural aftermaths of impact accelerated traumatic brain injury in rats: a model of comorbid depression and anxiety? Behav Brain Res 205:436–442

    Article  PubMed  Google Scholar 

  22. Stanford SC (2007) The open field test: reinventing the wheel. J Psychopharmacol 21:134–135

    Article  PubMed  Google Scholar 

  23. Cohen H, Matar MA, Zohar J (2011) The ‘cut-off behavioral criteria’ method—modeling clinical diagnostic criteria in animal studies of PTSD. In: Gouild TD (ed) Mood and anxiety related phenotypes in mice: characterization using behavioral tests, vol II. Humana Press c/o Springer Science, New York, pp 185–208

  24. Shinomol GK, Muralidhara (2007) Differential induction of oxidative impairments in brain regions of male mice following subchronic consumption of Khesari dhal (Lathyrus sativus) and detoxified Khesari dhal. Neurotoxicology 28:798–806

    Article  CAS  PubMed  Google Scholar 

  25. Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Ezymol 186:421–431

    Article  CAS  Google Scholar 

  26. Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Method Enzymol 233:357–363

    Article  CAS  Google Scholar 

  27. Sedlak J, Lindsay RH (1968) Estimation of total, protein bound, and non-protein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  28. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids. Anal Biochem 126:131–138

    Article  CAS  PubMed  Google Scholar 

  29. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  30. Beauchamp C, Fridovich I (1971) Superoxide dismutase: improved assays and an assay applicable to acryl amide gels. Anal Biochem 44:276–287

    Article  CAS  PubMed  Google Scholar 

  31. Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Method Enzymol 105:114–121

    Article  CAS  Google Scholar 

  32. Ellman GE, Courtney KD, Andersen JV, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  PubMed  Google Scholar 

  33. Dingova D, Leroy J, Check A, Garaj V, Krejci E, Hrabovska A (2014) Optimal detection of cholinesterase activity in biological samples: modifications to the standard Ellman’s assay. Anal Biochem 462:67–75

    Article  CAS  PubMed  Google Scholar 

  34. Bagh MB, Maiti AK, Jana S, Banerjee K, Roy A, Chakrabarti S (2008) Quinone and oxyradical scavenging properties of N-acetylcysteine prevent dopamine mediated inhibition of Na+, K+-ATPase and mitochondrial electron transport chain activity in rat brain: implications in the neuroprotective therapy of Parkinson’s disease. Free Radic Res 42(6):574–581

    Article  CAS  PubMed  Google Scholar 

  35. Liu Y, Peterson DA, Kimura H, Schubert D (1997) Mechanism of cellular 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem 69:581–593

    Article  CAS  PubMed  Google Scholar 

  36. King TS (1967) Preparation of succinate dehydrogenase and reconstitution of succinate oxidase. Methods Enzymol. Academic Press, New York, pp 322–325

    Google Scholar 

  37. Clark JB, Bates TE, Boakye P, Kuimov A, Land JM (1997) Investigation of mitochondrial defects in brain and skeletal muscle. In: Turner AJ, Bachelard HS (eds) Neurochemistry: a practical approach. Oxford University Press, Oxford, pp 151–174

    Google Scholar 

  38. Sottocasa GL, Kuylenstierna B, Ernster L, Bergstrand A (1967) An electron-transport system associated with the outer membrane of liver mitochondria. A biochemical and morphological study. J Cell Biol 32:415–438

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Griffiths DE, Houghton RL (1974) Studies on energy-linked reactions: modified mitochondrial ATPase of oligomycin-resistant mutants of Saccharomyces cerevisiae. Eur J Biochem 46:157–167

    Article  CAS  PubMed  Google Scholar 

  40. Fiske CH, Subbarow Y (1927) The nature of the “Inorganic phosphate” in voluntary muscle. Science 65(1686):401–403

    Article  CAS  PubMed  Google Scholar 

  41. Baraccaa A, Sgarbib G, Solaini G, Lenaz G (2003) Rhodamine 123 as a probe of mitochondrial membrane potential: evaluation of proton flux through F0 during ATP synthesis. Biochim Biophys Acta 1606:137–146

    Article  Google Scholar 

  42. Horvat A, Stanojevic I, Drakulic D, Velickovic N, Petrovic S, Milosevic M (2010) Effect of acute stress on NTPDase and 5′-nucleotidase activities in brain synaptosomes in different stages of development. Int J Dev Neurosci 28:175–182

    Article  CAS  PubMed  Google Scholar 

  43. Schetinger MRC, Porto N, Moretto MB, Morsch VM, Vieira V, Moro F, Neis RT, Bittencourt S, Bonacorso H, Zanatta N (2000) New benzodiazepines alter acetylcholinesterase and ATPDase activities. Neurochem Res 25:949–955

    Article  CAS  PubMed  Google Scholar 

  44. Heymann D, Reddington M, Kreutzberg GW (1984) Subcellular localization of 5′-nucleotidase in rat brain. J Neurochem 43:971–978

    Article  CAS  PubMed  Google Scholar 

  45. Cognato GP, Vuaden FC, Savio LE, Bellaver B, Casali E, Bogo MR, Souza DO, Sévigny J, Bonan CD (2011) Nucleoside triphosphate diphosphohydrolases role in the pathophysiology of cognitive impairment induced by seizure in early age. Neuroscience 180:191–200

    Article  CAS  PubMed  Google Scholar 

  46. Chtourou Y, Fetoui H, el Garoui M, Boudawara T, Zeghal N (2012) Improvement of cerebellum redox states and cholinergic functions contribute to the beneficial effects of silymarin against manganese-induced neurotoxicity. Neurochem Res 37(3):469–479

    Article  CAS  PubMed  Google Scholar 

  47. Sripetchwandee J, Pipatpiboon N, Chattipakorn N, Chattipakorn S (2014) Combined therapy of iron chelator and antioxidant completely restores brain dysfunction induced by iron toxicity. PLoS ONE 9(1):e85115

    Article  PubMed Central  PubMed  Google Scholar 

  48. Piloni NE, Fermandez V, Videla LA, Puntarulo S (2013) Acute iron overload and oxidative stress in brain. Toxicology 314(1):174–182

    Article  CAS  PubMed  Google Scholar 

  49. Crichton RR, Dexter DT, Ward RJ (2011) Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm 118:301–314

    Article  CAS  PubMed  Google Scholar 

  50. Nandar W, Neely EB, Unger E, Connor JR (2013) A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice. Biochim Biophys Acta 1832:729–741

    Article  CAS  PubMed  Google Scholar 

  51. Guo C, Wang P, Zhong ML, Wang T, Huang XS, Li JY, Wang ZY (2013) Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain. Neurochem Int 62(2):165–172

    Article  CAS  PubMed  Google Scholar 

  52. Sato H, Takahashi T, Sumitani K, Takatsu H, Urano S (2010) Glucocorticoid generates ROS to induce oxidative injury in the hippocampus, leading to impairment of cognitive function of rats. J Clin Biochem Nutr 47:224–232

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Maaroufi K, Ammari M, Jeljeli M, Roy V, Sakly M, Abdelmelek H (2009) Impairment of emotional behavior and spatial learning in adult Wistar rats by ferrous sulfate. Physiol Behav 96(2):343–349

    Article  CAS  PubMed  Google Scholar 

  54. Perez VP, de Lima MN, da Silva RS, Dornelles AS, Vedana G et al (2010) Iron leads to memory impairment that is associated with a decrease in acetylcholinesterase pathways. Curr Neurovasc Res 7:15–22

    Article  CAS  PubMed  Google Scholar 

  55. Maaroufi K, Had-Aissouni L, Melon C, Sakly M, Abdelmelek H, Poucet B, Save E (2014) Spatial learning, monoamines and oxidative stress in rats exposed to 900 MHz electromagnetic field in combination with iron overload. Behav Brain Res 258:80–89

    Article  CAS  PubMed  Google Scholar 

  56. Anderson W, Barrows M, Lopez F, Rogers S, Ortiz-Coffie A, Norman D, Hodges J, McDonald K, Barnes D, McCall S, Don JA, Ceremuga TE (2012) Investigation of the anxiolytic effects of naringenin, a component of Mentha aquatica, in the male Sprague-Dawley rat. Holist Nurs Pract 26(1):52–57

    Article  PubMed  Google Scholar 

  57. Yi LT, Li J, Li HC, Su DX, Quan XB, He XC, Wang XH (2012) Antidepressant-like behavioral, neurochemical and neuroendocrine effects of naringenin in the mouse repeated tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry 39(1):175–181

    Article  CAS  PubMed  Google Scholar 

  58. Pereira VS, Casarotto PC, Hiroaki-Sato VA, Sartim AG, Guimarães FS, Joca SR (2013) Antidepressant- and anticompulsive-like effects of purinergic receptor blockade: involvement of nitric oxide. Eur Neuropsychopharmacol 23(12):1769–1778

    Article  CAS  PubMed  Google Scholar 

  59. Jo YH, Role LW (2002) Cholinergic modulation of purinergic and GABAergic co-transmission at in vitro hypothalamic synapses. J Neurophysiol 88:2501–2508

    Article  CAS  PubMed  Google Scholar 

  60. Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H (2009) Purinergic signalling in the nervous system: an overview. Trends Neurosci 32(1):19–29

    Article  CAS  PubMed  Google Scholar 

  61. Schmatz R, Mazzanti CM, Spanevello R, Stefanello N, Gutierres J, Maldonado PA, Correa M, da Rosa CS, Becker L, Bagatini M, Goncalves JF, Jaques Jdos S, Schetinger MR, Morsch VM (2009) Ectonucleotidase and acetylcholinesterase activities in synaptosomes from the cerebral cortex of streptozotocin-induced diabetic rats and treated with resveratrol. Brain Res Bull 80:371–376

    Article  CAS  PubMed  Google Scholar 

  62. Spanevello RM, Mazzanti CM, Schmatz R, Thome G, Bagatini M, Correa M, Rosa C, Stefanello N, Belle LP, Moretto MB, Oliveira L, Morsch VM, Schetinger MR (2010) The activity and expression of NTPDase is altered in lymphocytes of multiple sclerosis patients. Clin Chim Acta 411:210–214

    Article  CAS  PubMed  Google Scholar 

  63. Zanini D, Schmatz R, Pimentel VC, Gutierres JM, Maldonado PA, Thome GR, Cardoso AM, Stefanello N, Oliveira L, Chiesa J, Leal DB, Morsch VM, Schetinger MR (2012) Lung cancer alters the hydrolysis of nucleotides and nucleosides in platelets. Biomed Pharmacother 66:40–45

    Article  CAS  PubMed  Google Scholar 

  64. Kaizer RR, Gutierres JM, Schmatz R, Spanevello RM, Morsch VM, Schetinger MR, Rocha JB (2010) In vitro and in vivo interactions of aluminum on NTPDase and AChE activities in lymphocytes of rats. Cell Immunol 265:133–138

    Article  CAS  PubMed  Google Scholar 

  65. Pohanka M (2014) Copper, aluminum, iron and calcium inhibit human acetylcholinesterase in vitro. Environ Toxicol Pharmacol 37(1):455–459

    Article  CAS  PubMed  Google Scholar 

  66. de Lima D, Roque GM, de Almeida EA (2013) In vitro and in vivo inhibition of acetylcholinesterase and carboxylesterase by metals in zebrafish (Danio rerio). Mar Environ Res 91:45–51

    Article  PubMed  Google Scholar 

  67. Ibrahim F, Andre C, Aljhni R, Gharbi T, Guillaume YC (2013) A molecular chromatographic approach to study the effects of OH· and NO on acetylcholinesterase activity. J Mol Catal B Enzym 94:136–140

    Article  CAS  Google Scholar 

  68. Mena NP, Urrutia PJ, Lourido F, Carrasco CM, Núñez MT (2015) Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders. Mitochondrion 21C:92–105

    Article  Google Scholar 

  69. Gao X, Campian JL, Qian M, Sun XF, Eaton JW (2009) Mitochondrial DNA damage in iron overload. J Biol Chem 284(8):4767–4775

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Ho PW, Ho JW, Liu HF, So DH, Tse ZH, Chan KH, Ramsden DB, Ho SL (2012) Mitochondrial neuronal uncoupling proteins: a target for potential disease-modification in Parkinson’s disease. Transl Neurodegener 1(1):3

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1–13

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Gao X, Qian M, Campian JL, Marshall J, Zhou Z, Roberts AM, Kang YJ, Prabhu SD, Sun XF, Eaton JW (2010) Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload. Free Radic Biol Med 49(3):401–407

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Baratli Y, Charles AL, Wolff V, Ben Tahar L, Smiri L, Bouitbir J, Zoll J, Piquard F, Tebourbi O, Sakly M, Abdelmelek H, Geny B (2013) Impact of iron oxide nanoparticles on brain, heart, lung, liver and kidneys mitochondrial respiratory chain complexes activities and coupling. Toxicol In Vitro 27(8):2142–2148

    Article  CAS  PubMed  Google Scholar 

  74. Pandya JD, Nukala VN, Sullivan PG (2013) Concentration dependent effect of calcium on brain mitochondrial bioenergetics and oxidative stress parameters. Front Neuroenerg 5:10

    Article  Google Scholar 

  75. Mattson MP (2007) Calcium and neurodegeneration. Aging Cell 6:337–350

    Article  CAS  PubMed  Google Scholar 

  76. He Q, Song N, Jia F, Xu H, Yu X, Xie J, Jiang H (2013) Role of α-synuclein aggregation and the nuclear factor E2-related factor 2/heme oxygenase-1 pathway in iron-induced neurotoxicity. Int J Biochem Cell Biol 45(6):1019–1030

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The present work was supported by the grants of DGRST (Appui a la Recherche Universitaire de base, ARUB, UR11ES70) Tunisia. The authors are also grateful to Kamel MAALOUL, English professor at the Faculty of Sciences of Sfax, for having proofread the manuscript.

Conflict of interest

None of the authors has any conflict of interest.

Ethical standard

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Author information

Authors and Affiliations

  1. Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Life Sciences Department, Faculty of Sciences, University of Sfax, Street Soukra Km 3.5, BP 1171, 3000, Sfax, Tunisia

    Yassine Chtourou, Ahlem Ben Slima, Radhouane Gdoura & Hamadi Fetoui

Authors
  1. Yassine Chtourou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahlem Ben Slima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Radhouane Gdoura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hamadi Fetoui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yassine Chtourou.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chtourou, Y., Slima, A.B., Gdoura, R. et al. Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus. Neurochem Res 40, 1563–1575 (2015). https://doi.org/10.1007/s11064-015-1627-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-015-1627-9

Keywords

Search

Navigation