Melatonin Ameliorates Cadmium-Induced Affective and Cognitive Impairments and Hippocampal Oxidative Stress in Rat

Biological Trace Element Research volume 199, pages1445–1455(2021)Cite this article

Abstract

The present work aims to evaluate the effect of melatonin (Mel) on affective and cognitive disorders induced by chronic exposure to Cadmium (Cd). Male and female Wistar rats received either an intraperitoneal injection of saline solution NaCl (0.9%), Mel (4 mg/kg), Cd (1 mg/kg), or Cd (1 mg/kg) + Mel (4 mg/kg) for 8 weeks. Behavioral disorders were evaluated by different tests mainly the open field and elevated plus maze tests for anxiety-like behavior, forced swimming test (FST) for depression-like behavior, and the Y-maze and Morris water maze (MWM) tests for cognitive disorders. Thereafter, oxidative stress indices and histology of the hippocampus were evaluated. The results confirm that Cd administration has anxiogenic-like effects in both anxiety tests and depressive-like effects in the FST and leads to memory and learning disabilities in the Y-maze and MWM. We also report that Mel counteracts these neurobehavioral disorders. Biochemical assays showed that rats intoxicated with Cd significantly increased levels of nitric oxide (NO) and lipid peroxidation (LPO), while the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly decreased in the hippocampus. In contrast, Mel administration attenuates the Cd-induced changes. The histopathological studies in the hippocampus of rats also supported that Mel markedly reduced the Cd-induced neuronal loss in CA3 sub-region. Overall, our results suggest that Mel could be used to protect against Cd-induced neurobehavioral changes via its antioxidant properties in the hippocampus. The effects of Cd and Mel are sex-dependent, knowing that Cd is more harmful in males, while Mel is more protective in females.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

US$ 39.95

Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. 1.

    Lamtai M, Chaibat J, Ouakki S, Berkiks I, Rifi E, El Hessni A, Mesfioui A, Hbibi AT, Ahyayauch H, Essamri A, Ouichou A (2018) Effect of Chronic Administration of Cadmium on Anxiety-Like, Depression-Like and Memory Deficits in Male and Female Rats: Possible Involvement of Oxidative Stress Mechanism. J Behav Brain Sci 8:240–268. https://doi.org/10.4236/jbbs.2018.85016

    CAS  Article  Google Scholar 

  2. 2.

    Richter P, Faroon O, Pappas RS (2017) Cadmium and cadmium/zinc ratios and tobacco-related morbidities. Int J Environ Res Public Health 14:1154. https://doi.org/10.3390/ijerph14101154

    CAS  Article  PubMed Central  Google Scholar 

  3. 3.

    Karri V, Schuhmacher M, Kumar V (2016) Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain. Environ Toxicol Pharmacol 48:203–213. https://doi.org/10.1016/j.etap.2016.09.016

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Batool Z, Agha F, Tabassum S, Batool TS, Siddiqui RA, Haider S (2019) Prevention of cadmium-induced neurotoxicity in rats by essential nutrients present in nuts. Acta Neurobiol Exp (Wars) 79:169–183. https://doi.org/10.21307/ane-2019-015

    Article  Google Scholar 

  5. 5.

    Wang B, Du Y (2013) Review article cadmium and its neurotoxic effects. Oxid Med Cell Longev 2013:1–12. https://doi.org/10.1155/2013/898034

    CAS  Article  Google Scholar 

  6. 6.

    Ciesielski T, Weuve J, Bellinger DC, Schwartz J, Lanphear B, Wright RO (2012) Cadmium exposure and neurodevelopmental outcomes in U.S. Children. Environ Health Perspect 120:758–763

    CAS  Article  Google Scholar 

  7. 7.

    Zghari O, Rezqaoui A, Ouakki S, Lamtai M, Chaibat J, Mesfioui A, El Hessni A, Rifi E-H, Essamri A, Ouichou A (2018) Effect of Chronic Aluminum Administration on Affective and Cognitive Behavior in Male and Female Rats. J Behav Brain Sci 8:179–196. https://doi.org/10.4236/jbbs.2018.84012

    CAS  Article  Google Scholar 

  8. 8.

    Lamtai M, Chaibat J, Ouakki S, Zghari O, Mesfioui A, El Hessni A, Rifi E-H, Marmouzi I, Essamri A, Ouichou A (2018) Effect of chronic administration of nickel on affective and cognitive behavior in male and female rats: possible implication of oxidative stress pathway. Brain Sci 8:141. https://doi.org/10.3390/brainsci8080141

    CAS  Article  PubMed Central  Google Scholar 

  9. 9.

    Lamtai M, Ouakki S, Zghari O, Mesfioui A, El Hessni A, Ouichou A (2019) Affective behavior dysregulation was induced by chronic administration of copper in Wistar rats. Neurosci Med 10:134–149. https://doi.org/10.4236/nm.2019.102009

    CAS  Article  Google Scholar 

  10. 10.

    Rehman SU, Ikram M, Ullah N, Alam SI, Park HY, Badshah H, Choe K, Ok Kim M (2019) Neurological enhancement effects of melatonin against brain injury-induced oxidative stress, neuroinflammation, and neurodegeneration via AMPK/CREB signaling. Cells 8:760. https://doi.org/10.3390/cells8070760

    CAS  Article  PubMed Central  Google Scholar 

  11. 11.

    Mahmood D, Muhammad BY, Albdulghani M, Anwar J, el-Lebban N, Haider M (2016) Corrigendum to “Advancing role of melatonin in the treatment of neuropsychiatric disorders.”. Egypt J Basic Appl Sci 3:398–398. https://doi.org/10.1016/j.ejbas.2016.08.005

    Article  Google Scholar 

  12. 12.

    Ouakki S, El Mrabet FZ, El Hessni A, Mesfioui A, Pévet P, Ouichou A (2013) Conversion of L-Tryptophan into Melatonin Is the Possible Action Pathway Involved in the Effect of L-Tryptophan on Antidepressant-Related Behavior in Female Rats: Analysis of the Influence of Treatment Duration. J Behav Brain Sci 3:362–372. https://doi.org/10.4236/jbbs.2013.34036

    CAS  Article  Google Scholar 

  13. 13.

    El Mrabet FZ, Lagbouri I, Mesfioui A, El Hessni A, Ouichou A (2012) The influence of gonadectomy on anxiolytic and antidepressant effects of melatonin in male and female Wistar rats: a possible implication of sex hormones. Neurosci Med 3:162–173. https://doi.org/10.4236/nm.2012.32021

    Article  Google Scholar 

  14. 14.

    Kocic G, Tomovic K, Kocic H, Sokolovic D, Djordjevic B, Stojanovic S, Arsic I, Smelcerovic A (2017) Antioxidative, membrane protective and antiapoptotic effects of melatonin, in silico study of physico-chemical profile and efficiency of nanoliposome delivery compared to betaine. RSC Adv 7:1271–1281. https://doi.org/10.1039/C6RA24741E

    CAS  Article  Google Scholar 

  15. 15.

    Rodriguez C, Mayo JC, Sainz RM, Antolín I, Herrera F, Martín V, Reiter RJ (2004) Regulation of antioxidant enzymes: A significant role for melatonin. J Pineal Res 36:1–9. https://doi.org/10.1046/j.1600-079X.2003.00092.x

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    El Mrabet FZ, Ouaaki S, Mesfioui A, El Hessni A, Ouichou A (2012) Pinealectomy and exogenous melatonin regulate anxiety-like and depressive-like behaviors in male and female Wistar rats. Neurosci Med 3:394–403. https://doi.org/10.4236/nm.2012.34049

    CAS  Article  Google Scholar 

  17. 17.

    Carola V, D’Olimpio F, Brunamonti E, Mangia F, Renzi P (2002) Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice. Behav Brain Res 134:49–57. https://doi.org/10.1016/S0166-4328(01)00452-1

    Article  PubMed  Google Scholar 

  18. 18.

    Naranjo-Rodriguez EB, Osornio AO, Hernandez-Avitia E, Mendoza-Fernandez V, Escobar A (2000) Anxiolytic-like actions of melatonin, 5-metoxytryptophol, 5-hydroxytryptophol and benzodiazepines on a conflict procedure. Prog Neuro-Psychopharmacology Biol Psychiatry 24:117–129. https://doi.org/10.1016/S0278-5846(99)00075-5

    CAS  Article  Google Scholar 

  19. 19.

    Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391. https://doi.org/10.1016/0014-2999(78)90118-8

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Sierksma ASR, Van Den Hove DLA, Pfau F, Philippens M, Bruno O, Fedele E, Ricciarelli R, Steinbusch HWM, Vanmierlo T, Prickaerts J (2014) Improvement of spatial memory function in APPswe/PS1dE9 mice after chronic inhibition of phosphodiesterase type 4D. Neuropharmacology 77:120–130. https://doi.org/10.1016/j.neuropharm.2013.09.015

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Method 11:47–60

    CAS  Article  Google Scholar 

  22. 22.

    Kaoud H a, Kamel MM, Abdel-Razek a H, Kamel GM, Ahmed K a (2010) Neurobehavioural, neurochemical and neuromorphological effects of cadmium in male rats. J Am Sci 202:54–63

    Google Scholar 

  23. 23.

    Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid Peroxidation. Methods Enzymol 186:421–431. https://doi.org/10.1016/0076-6879(90)86135-I

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Chao CC, Hu S, Molitor TW, Shaskan EG, Peterson PK, Chao CC, Hu S, Molitor TW, Shaskan EG, Peterson PK (1992) injury via a nitric oxide mechanism. Activated microglia mediate oxide neuronal cell injury via a nitric mechanism’. J Immunol 149:2736–2741

    CAS  PubMed  Google Scholar 

  25. 25.

    Beauchamp C, Fridovich I (1971) Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem 44:276–287. https://doi.org/10.1016/0003-2697(71)90370-8

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Aebi H (1984) Catalase in Vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/S0076-6879(84)05016-3

    CAS  Article  Google Scholar 

  27. 27.

    Jalili C, Salahshoor MR, Pourmotabbed A, Moradi S, Roshankhah SH, Darehdori AS, Motaghi M (2014) The effects of aqueous extract of Boswellia Serrata on hippocampal region CA1 and learning deficit in kindled rats. Res Pharm Sci 9:351–358

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Esteban S, Garau C, Aparicio S, Moranta D, Barceló P, Fiol MA, Rial R (2010) Chronic melatonin treatment and its precursor L-tryptophan improve the monoaminergic neurotransmission and related behavior in the aged rat brain. J Pineal Res 48:170–177. https://doi.org/10.1111/j.1600-079X.2009.00741.x

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Wang H, Zhang L, Abel GM, Storm DR, Xia Z (2018) Cadmium exposure impairs cognition and olfactory memory in male C57BL/6 mice. Toxicol Sci 161:87–102. https://doi.org/10.1093/toxsci/kfx202

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Pulido G, Treviño S, Brambila E, Vazquez-Roque R, Moreno-Rodriguez A, Peña Rosas U, Moran-Perales JL, Handal Silva A, Guevara J, Flores G, Diaz A (2019) The administration of cadmium for 2, 3 and 4 months causes a loss of recognition memory, promotes neuronal hypotrophy and apoptosis in the hippocampus of rats. Neurochem Res 44:485–497. https://doi.org/10.1007/s11064-018-02703-2

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Ali T, Kim MO (2015) Melatonin ameliorates amyloid beta-induced memory deficits, tau hyperphosphorylation and neurodegeneration via PI3/Akt/GSk3β pathway in the mouse hippocampus. J Pineal Res 59:47–59. https://doi.org/10.1111/jpi.12238

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    El-Sherif Y, Tesoriero J, Hogan MV, Wieraszko A (2003) Melatonin regulates neuronal plasticity in the hippocampus. J Neurosci Res 72:454–460. https://doi.org/10.1002/jnr.10605

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Neely CLC, Lippi SLP, Lanzirotti A, Flinn JM (2019) Localization of free and bound metal species through X-Ray synchrotron fluorescence microscopy in the rodent brain and their relation to behavior. Brain Sci 9:74. https://doi.org/10.3390/brainsci9040074

    CAS  Article  PubMed Central  Google Scholar 

  34. 34.

    Musshoff U, Riewenherm D, Berger E, Fauteck JD, Speckmann EJ (2002) Melatonin receptors in rat hippocampus: molecular and functional investigations. Hippocampus 12:165–173. https://doi.org/10.1002/hipo.1105

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Maes M, Galecki P, Chang YS, Berk M (2011) A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuro-Psychopharmacology Biol Psychiatry 35:676–692. https://doi.org/10.1016/j.pnpbp.2010.05.004

    CAS  Article  Google Scholar 

  36. 36.

    Rahman MF, Wang J, Patterson TA, Saini UT, Robinson BL, Newport GD, Murdock RC, Schlager JJ, Hussain SM, Ali SF (2009) Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticles. Toxicol Lett 187:15–21. https://doi.org/10.1016/j.toxlet.2009.01.020

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Jangra A, Lukhi MM, Sulakhiya K, Baruah CC, Lahkar M (2014) Protective effect of mangiferin against lipopolysaccharide-induced depressive and anxiety-like behaviour in mice. Eur J Pharmacol 740:337–345. https://doi.org/10.1016/j.ejphar.2014.07.031

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Sulakhiya K, Kumar P, Jangra A, Dwivedi S, Hazarika NK, Baruah CC, Lahkar M (2014) Honokiol abrogates lipopolysaccharide-induced depressive like behavior by impeding neuroinflammation and oxido-nitrosative stress in mice. Eur J Pharmacol 744:124–131. https://doi.org/10.1016/j.ejphar.2014.09.049

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Taniguti EH, Ferreira YS, Stupp IJV, Fraga-Junior EB, Mendonça CB, Rossi FL, Ynoue HN, Doneda DL, Lopes L, Lima E, Buss ZS, Vandresen-Filho S (2018) Neuroprotective effect of melatonin against lipopolysaccharide-induced depressive-like behavior in mice. Physiol Behav 188:270–275. https://doi.org/10.1016/j.physbeh.2018.02.034

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Abdel Moneim AE, Bauomy AA, Diab MMS, Shata MTM, Al-Olayan EM, El-Khadragy MF (2014) The protective effect of Physalis peruviana L. against cadmium-induced neurotoxicity in rats. Biol Trace Elem Res 160:392–399. https://doi.org/10.1007/s12011-014-0066-9

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Abdalla FH, Schmatz R, Cardoso AM, Carvalho FB, Baldissarelli J, de Oliveira JS, Rosa MM, Gonalves Nunes MA, Rubin MA, IBM d C, Barbisan F, Dressler VL, Pereira LB, MRC S, Morsch VM, Gonalves JF, Mazzanti CM (2014) Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: Possible involvement of the acetylcholinesterase and Na+,K + -ATPase activities. Physiol Behav 135:152–167. https://doi.org/10.1016/j.physbeh.2014.06.008

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Garry PS, Ezra M, Rowland MJ, Westbrook J, Pattinson KTS (2015) The role of the nitric oxide pathway in brain injury and its treatment - From bench to bedside. Exp Neurol 263:235–243. https://doi.org/10.1016/j.expneurol.2014.10.017

    CAS  Article  Google Scholar 

  43. 43.

    Förstermann U, Sessa WC (2012) Nitric oxide synthases: Regulation and function. Eur Heart J 33:829–837. https://doi.org/10.1093/eurheartj/ehr304

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Poliandri AHB, Esquifino AI, Cano P, Jiménez V, Lafuente A, Cardinali DP, Duvilanski BH (2006) In vivo protective effect of melatonin on cadmium-induced changes in redox balance and gene expression in rat hypothalamus and anterior pituitary. J Pineal Res 41:238–246. https://doi.org/10.1111/j.1600-079X.2006.00360.x

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Moncada S, Bolaños JP (2006) Nitric oxide, cell bioenergetics and neurodegeneration. J Neurochem 97:1676–1689. https://doi.org/10.1111/j.1471-4159.2006.03988.x

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Albendea CD, Gómez-Trullén EM, Fuentes-Broto L, Miana-Mena FJ, Millán-Plano S, Reyes-Gonzales MC, Martínez-Ballarín E, García JJ (2007) Melatonin reduces lipid and protein oxidative damage in synaptosomes due to aluminium. J Trace Elem Med Biol 21:261–268. https://doi.org/10.1016/j.jtemb.2007.04.002

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    El-Missiry MA, Shalaby F (2000) Role of β-carotene in ameliorating the cadmium-induced oxidative stress in rat brain and testis. J Biochem Mol Toxicol 14:238–243. https://doi.org/10.1002/1099-0461(2000)14:5<238::AID-JBT2>3.0.CO;2-X

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Mazhoudi S, Chaoui A, Ghorbal MH, El Ferjani E (1997) Response of antioxidant enzymes to excess copper in tomato (Lycopersicon esculentum, Mill.). Plant Sci 127:129–137. https://doi.org/10.1016/S0168-9452(97)00116-7

    CAS  Article  Google Scholar 

  49. 49.

    Das P, Samantaray S, Rout GR (1997) Studies on cadmium toxicity in plants: A review. Environ. Pollut. 98:29–36

    CAS  Article  Google Scholar 

  50. 50.

    Zhang L, Zhang HQ, Liang XY, Zhang HF, Zhang T, Liu FE (2013) Melatonin ameliorates cognitive impairment induced by sleep deprivation in rats: Role of oxidative stress, BDNF and CaMKII. Behav Brain Res 256:72–81. https://doi.org/10.1016/j.bbr.2013.07.051

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Koh PO (2008) Melatonin regulates nitric oxide synthase expression in ischemic brain injury. J Vet Med Sci 70:747–750. https://doi.org/10.1292/jvms.70.747

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Deng WG, Tang ST, Tseng HP, Wu KK (2006) Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding. Blood 108:518–524. https://doi.org/10.1182/blood-2005-09-3691

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Pandi-Perumal SR, Bahammam AS, Brown GM, Spence DW, Bharti VK, Kaur C, Hardeland R, Cardinali DP (2013) Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes. Neurotox. Res. 23:267–300

    CAS  Article  Google Scholar 

  54. 54.

    Kotler M, Rodríguez C, Sáinz RM, Antolín I, Menéndez-Peláez A (1998) Melatonin increases gene expression for antioxidant enzymes in rat brain cortex. J Pineal Res 24:83–89. https://doi.org/10.1111/j.1600-079X.1998.tb00371.x

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Leutgeb S, Leutgeb JK, Barnes CA, Moser EI, McNaughton BL, Moser MB (2005) Neuroscience: Independent codes for spatial and episodic memory in hippocampal neuronal ensembles. Science (80- ) 309:619–623. https://doi.org/10.1126/science.1114037

  56. 56.

    Zhu C, Xu Q, Wang C, Mao Z, Lin N (2017) Evidence that CA3 is Underling the Comorbidity Between Pain and Depression and the Co-curation by Wu-Tou decoction in Neuropathic Pain. Sci Rep 7:1–14. https://doi.org/10.1038/s41598-017-12184-y

    CAS  Article  Google Scholar 

  57. 57.

    Halliwell B (2006) Oxidative stress and neurodegeneration: Where are we now? J Neurochem 97:1634–1658. https://doi.org/10.1111/j.1471-4159.2006.03907.x

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    Soleimani E, Goudarzi I, Abrari K, Lashkarbolouki T (2017) Maternal administration of melatonin prevents spatial learning and memory deficits induced by developmental ethanol and lead co-exposure. Physiol Behav 173:200–208. https://doi.org/10.1016/j.physbeh.2017.02.012

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Zhou T, Guo J, Zhang J, Xiao H, Qi X, Wu C, Chang X, Zhang Y, Liu Q, Zhou Z (2019) Sex-specific differences in cognitive abilities associated with childhood cadmium and manganese exposures in school-age children: a prospective cohort study. Biol Trace Elem Res 193:89–99. https://doi.org/10.1007/s12011-019-01703-9

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Edinger KL, Frye CA (2006) Intrahippocampal administration of an androgen receptor antagonist, flutamide, can increase anxiety-like behavior in intact and DHT-replaced male rats. Horm Behav 50:216–222. https://doi.org/10.1016/j.yhbeh.2006.03.003

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Elharabi FB, Gatie SJ (2010) The effects of Cadmium Chlorid ( CdCl on the functions of reproductive system of the male mice). J Biol Sci Kufa Univ 2:10

    Google Scholar 

  62. 62.

    Brotto LA, Barr AM, Gorzalka BB (2000) Sex differences in forced-swim and open-field test behaviours after chronic administration of melatonin. Eur J Pharmacol 402:87–93. https://doi.org/10.1016/S0014-2999(00)00491-X

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Golombek DA, PéVet P, Cardinali DP (1996) Melatonin effects on behavior: possible mediation by the central GABAergic system. Neurosci Biobehav Rev 20:403–412. https://doi.org/10.1016/0149-7634(95)00052-6

    CAS  Article  PubMed  Google Scholar 

Download references

Funding

No fund was received or no funding organization was involved in this study.

Author information

Author notes

  1. Sofia Azirar equally contributed to the work.

Affiliations

  1. Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofail University, 133, 14000, Kenitra, BP, Morocco

    Mouloud Lamtai, Sofia Azirar, Oussama Zghari, Sihame Ouakki, Aboubaker El Hessni, Abdelhalem Mesfioui & Ali Ouichou

Authors
  1. Mouloud Lamtai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sofia Azirar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oussama Zghari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sihame Ouakki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aboubaker El Hessni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abdelhalem Mesfioui
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ali Ouichou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Mouloud Lamtai and Sofia Azirar performed the experiments, analyzed the data and wrote the paper. Sihame Ouakki and Oussama Zghari participated in behavioral analysis and statistical significance. Abdelhalem Mesfioui and Aboubaker El Hessni reviewed and provided comments on the content and interpretation of the manuscript. Ali Ouichou supervised the work, revised and approved the manuscript

Corresponding author

Correspondence to Mouloud Lamtai.

Ethics declarations

Conflict of Interest

There are no conflicts of interests with other organizations.

Ethics Approval

The experimental procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Animal Ethics Committee (Local Institutional Research Committee).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lamtai, M., Azirar, S., Zghari, O. et al. Melatonin Ameliorates Cadmium-Induced Affective and Cognitive Impairments and Hippocampal Oxidative Stress in Rat. Biol Trace Elem Res 199, 1445–1455 (2021). https://doi.org/10.1007/s12011-020-02247-z

Download citation

Keywords

  • Cadmium
  • Melatonin
  • Anxiety-like
  • Depression-like
  • Memory
  • Oxidative stress