Skip to main content
Log in

Alteration in cognitive behaviour, brain antioxidant enzyme activity and their gene expression in F1 generation mice, following Cd exposure during the late gestation period: modulation by quercetin

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

We investigated whether in-utero Cd(II) chloride exposure of the dams between 14th to 21st day of gestation affects memory and learning, oxidative stress, antioxidant enzyme activity and their gene expression in brain of the pups in their adulthood. In the Morris water maze, cadmium (Cd) exposure impaired spatial memory which was reversed following co-treatment with quercetin (100 mg/kg). In the passive avoidance paradigm, retention memory was adversely affected but was significantly reversed by co treatment with quercetin (25, 50, 100 mg/kg). The malondialdehyde and catalase (CAT) levels and glutathione-S-transferase (GST) activity were increased significantly in Cd-treated group, but were reversed by quercetin (all doses). The gene expression for CAT and GST in brain tissue of Cd treated animals also increased many folds as compared to the control, and this effect was decreased on co-treatment with quercetin (all doses), thus matching with the respective enzyme activities. Quercetin (25 mg/kg) when co-treated with Cd caused a decrease in GST activity compared to control, which points towards a complex interplay with oxidative free radicals and promoters and transcription factors. Thus, Cd exposure during late gestation causes impaired spatial and retention memory in the next generation which may be due to alteration of activity as well as gene expression of the antioxidant enzymes, CAT and GST. Quercetin may offer some protection of memory impairment probably by modulating these effects.

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

Access this article

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

  • Abnosi MH, Golami S (2017) Cadmium chloride treatment of rats significantly impairs membrane integrity of mesenchymal stem cells via electrolyte imbalance and lipid peroxidation, a possible explanation of cd related osteoporosis. Iran J Basic Med Sci 20:280–287

    PubMed  PubMed Central  Google Scholar 

  • Acharya U, Mishra M, Patro J, Panda M (2008) Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium. Reprod Toxicol 25:84–88

    Article  CAS  Google Scholar 

  • Amamou F, Nemmiche S, Meziane RK, Didi A, Yazit SM, Chabane-Sari D (2015) Protective effect of olive oil and colocynth oil against cadmium-induced oxidative stress in the liver of Wistar rats. Food Chem Toxicol 78:177–184

    Article  CAS  Google Scholar 

  • Batool Z, Agha F, Ahmad S, Liaquat L, Tabassum S, Khaliq S, Anis L, Sajid I, Emad S, Perveen T, Haider S (2017) Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond andwalnut supplementation: role of cholinergic function. Pak J Pharm Sci 30(1 Suppl):273–279

    PubMed  Google Scholar 

  • Brandeis R, Brandys Y, Yehuda S (1989) The use of the Morris water maze in the study of memory and learning. Int J Neurosci 48:29–69

    Article  CAS  Google Scholar 

  • Chen JY, Lee YM, Zhao D, Mak NK, Wong RN, Chan WH, Cheung NH (2010) Quantumdot-mediated photoproduction of reactive oxygen species for cancer cellannihilation. PhotochemPhotobiol 86:431–437

    CAS  Google Scholar 

  • Dharmadasa P, Kim N, Thunders M (2017) Maternal cadmium exposure and impact onfoetal gene expression through methylation changes. Food Chem Toxicol 109(Pt 1):714–720

    Article  CAS  Google Scholar 

  • Dokumacioglu E, Iskender H, Yenice G, Kapakin KAT, Sevim C, Hayirli A, Saral S, Comakli S (2018) Effects of astaxanthin on biochemical and histopathological parameters related to oxidative stress on testes of rats on high fructose regime Andrologiae 13042

  • Ellman GL (1959) Tissue sulphydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  Google Scholar 

  • Fatokun AA, Stone TW, Smith RA (2007) Hydrogen peroxide mediates damage by xanthine and xanthine oxidase in cerebellar granule neuronal cultures. Neurosci Lett 416:34–38

    Article  CAS  Google Scholar 

  • Gallegos CE, Baier CJ, Bartos M, Bras C, Domínguez S, Mónaco N, Gumilar F, Giménez MS, Minetti A (2018) Perinatal glyphosate-based herbicide exposure in rats alters brain antioxidant status, glutamate and acetylcholine metabolism and affects recognition memory. Neurotox Res. https://doi.org/10.1007/s12640-018-9894-2 [Epub ahead of print]

    Article  CAS  Google Scholar 

  • Ganesan S, Keating AF (2016) Bisphenol A-induced ovotoxicity involves DNA damage induction to which the ovary mounts a protective response indicated by increased expression of proteins involved in DNA repair and xenobiotic biotransformation. Toxicol Sci 152:169–180

    Article  CAS  Google Scholar 

  • Gupta S, Garg GR, Bharal N, Mediratta PK, Banerjee BD, Sharma KK (2009) Reversal of propoxur-induced impairment of step-down passive avoidance, transfer latency and oxidative stress by piracetam and ascorbic acid in rats. Environ Toxicol Pharmacol 28:403–408

    Article  CAS  Google Scholar 

  • Haider S, Anis L, Batool Z, Sajid I, Naqvi F, Khaliq S, Ahmed S (2015) Short termcadmium administration dose dependently elicits immediate biochemical, neurochemical and neurobehavioral dysfunction in male rats. Metab Brain Dis 30:83–92

    Article  CAS  Google Scholar 

  • Halder S, Kar R, Galav V, Mehta AK, Bhattacharya SK, Mediratta PK, Banerjee BD (2016a) Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin. Drug Chem Toxicol 39:272–278

    Article  CAS  Google Scholar 

  • Halder S, Kar R, Mehta AK, Bhattacharya SK, Mediratta PK, Banerjee BD (2016b) Quercetin modulates the effects of chromium exposure on learning, memory and antioxidant enzyme activity in F1 generation mice. Biol Trace Elem Res 171:391–398

    Article  CAS  Google Scholar 

  • Halder S, Mehta AK, Kar R, Mustafa M, Mediratta PK, Sharma KK (2011) Clove oil reverses learning and memory deficits in scopolamine-treated mice. Planta Med 77:830–834

    Article  CAS  Google Scholar 

  • Haleagrahara N, Siew CJ, Mitra NK, Kumari M (2011) Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum. Neurosci Lett 500:139–143

    Article  CAS  Google Scholar 

  • Hasanuzzaman M, Nahar K, Anee TI, Fujita M (2017) Exogenous silicon attenuates cadmium-induced oxidative stress in Brassica napus L. by modulating ASA-GSH pathway and glyoxalase system. Front plant Sci 8:1061

    Article  Google Scholar 

  • Hong J, Wang Y, McDermott S, Cai B, Aelion CM, Lead J (2016) The use of aphysiologically-based extraction test to assess relationships betweenbioaccessible metals in urban soil and neurodevelopmental conditions in children. Environ Pollut 212:9–17

    Article  CAS  Google Scholar 

  • Hu M, Wu F, Yuan M, Li Q, Gu Y, Wang Y, Liu Q (2015) Antioxidant responses of triangle sail mussel Hyriopsiscumingii exposed to harmful algae Microcystis aeruginosa and hypoxia. Chemosphere 139:541–549

    Article  CAS  Google Scholar 

  • Hussien HM, Abd-Elmegied A, Ghareeb DA, Hafez HS, Ahmed HEA, El-Moneam NA (2018) Neuroprotective effect of berberine against environmental heavy metals-induced neurotoxicity and Alzheimer's-like disease in rats. Food Chem Toxicol 111:432–444

    Article  CAS  Google Scholar 

  • Jin Y, Liu L, Zhang S, He R, Wu Y, Chen G, Fu Z (2016) Cadmium exposure to murine macrophages decreases their inflammatory responses and increases their oxidative stress. Chemosphere 144:168–175

    Article  CAS  Google Scholar 

  • Kantar Gok D, Hidisoglu E, Ocak GA, Er H, Acun AD, Yargıcoglu P (2018) Protective role of rosmarinic acid on amyloid beta 42-induced echoic memory decline: implication of oxidative stress and cholinergic impairment. Neurochem Int 118:1–13

    Article  CAS  Google Scholar 

  • Li R, Luo X, Zhu Y, Zhao L, Li L, Peng Q, Ma M, Gao Y (2017) ATM signals to AMPK to promote autophagy and positively regulate DNA damage in response to cadmium-induced ROS in mouse spermatocytes. Environ Pollut 231(Pt2):1560–1568

    Article  CAS  Google Scholar 

  • Lin Y, Miao LH, Pan WJ, Huang X, Dengu JM, Zhang WX, Ge XP, Liu B, Ren MC, Zhou QL, Xie J, Pan LK, Xi BW (2018) Effect of nitrite exposure on the antioxidant enzymes and glutathione system in the liver of bighead carp, Aristichthysnobilis. Fish Shellfish Immunol 76:126–132

    Article  CAS  Google Scholar 

  • Liu XR, Wang YY, Fan HR, Wu CJ, Kumar A, Yang LG (2016) Preventive effects of β-cryptoxanthin against cadmium-induced oxidative stress in the rat testis. Asian J Androl 18:920–924

    CAS  PubMed  PubMed Central  Google Scholar 

  • Luck H (1974) Estimation of catalase activity. In: Bergmeyer U (ed) methods of enzymology., academic press New York: 885

  • Luo Y, McCullough LE, Tzeng JY, Darrah T, Vengosh A, Maguire RL, Maity A, Samuel-Hodge C, Murphy SK, Mendez MA, Hoyo C (2017) Maternal blood cadmium, lead and arsenic levels, nutrient combinations, and offspring birthweight. BMC Public Health 17:354

    Article  Google Scholar 

  • Mannervik B, Danielson UH (1988) Glutathione transferases--structure and catalytic activity. CRC Crit Rev Biochem 23:283–337

    Article  CAS  Google Scholar 

  • Mao T, Han C, Wei B, Zhao L, Zhang Q, Deng R, Liu J, Luo Y, Zhang Y (2018) Protective effects of quercetin against cadmium chloride-induced oxidative injury in goat sperm and zygotes. Biol Trace Elem Res. https://doi.org/10.1007/s12011-018-1255-8 [Epub ahead of print]

    Article  CAS  Google Scholar 

  • Mateen S, Moin S, Khan AQ, Zafar A, Fatima N (2016) Increased reactive oxygen species formation and oxidative stress in rheumatoid arthritis. PLoS One 11:e0152925

    Article  Google Scholar 

  • Mehta KD, Mehta AK, Halder S, Khanna N, Tripathi AK, Sharma KK (2014) Protective effect of melatonin on propoxur-induced impairment of memory and oxidative stress in rats. Environ Toxicol 29:705–713

    Article  CAS  Google Scholar 

  • Morris RGM, Garrud P, Rawlins JN, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683

    Article  CAS  Google Scholar 

  • Nikolić-Kokić A, Stević Z, Blagojević D, Davidović B, Jones DR, Spasić MB (2006) Alterations in anti-oxidative defence enzymes in erythrocytes from sporadicamyotrophic lateral sclerosis (SALS) and familial ALS patients. Clin Chem Lab Med 44:589–593

    Article  Google Scholar 

  • Nikolić TV, Kojić D, Orčić S, Batinić D, Vukašinović E, Blagojević DP, Purać J (2016) The impact of sublethal concentrations of cu, Pb and cd on honey bee redox status, superoxide dismutase and catalase in laboratory conditions. Chemosphere 164:98–105

    Article  Google Scholar 

  • Niu Y, Cao W, Zhao Y, Zhai H, Zhao Y, Tang X, Chen Q (2018) The levels of oxidative stress and antioxidant capacity in hibernating Nanoranaparkeri. Comp BiochemPhysiolA Mol Integr Physiol 219-220:19–27

    Article  CAS  Google Scholar 

  • Nones J, Spohr TC, Gomes FC (2012) Effects of the flavonoid hesperidin in cerebral cortical progenitors in vitro: indirect action through astrocytes. Int J Dev Neurosci 30:303–313

    Article  CAS  Google Scholar 

  • Ognjanovic B, Markovic S, Dordevic N et al (2010) Cadmium-induced lipid peroxidation and changes in antioxidant defense system in the rat testes: protective role of coenzyme Q10 and vitamin E. ReprodToxicol 29:191–197

    CAS  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  Google Scholar 

  • Pinto A, Bonucci A, Maggi E, Corsi M, Businaro R (2018)Anti-oxidant and anti-inflammatory activity of ketogenic diet: new perspectives for neuroprotection in Alzheimer's disease. Antioxidants (Basel)7,pii: E63

  • Rinaldi M, Micali A, Marini H, Adamo EB, Puzzolo D, Pisani A, Trichilo V, Altavilla D, Squadrito F, Minutoli L (2017) Cadmium, organ toxicity and therapeutic approaches: a review on brain, kidney and testis damage. Curr Med Chem 24:3879–3893

    Article  CAS  Google Scholar 

  • Sbartai H, Djebar MR, Sbartai I, Berrabbah H (2012) Bioaccumulation of cadmium and zinc in tomato (Lycopersiconesculentum L.). C R Biol 335:585–593

    Article  CAS  Google Scholar 

  • Scholten SD, Sergeev IN (2013) Long-term quercetin supplementation reduces lipidperoxidation but does not improve performance in endurance runners. J Sports Med 12:53–61

    Google Scholar 

  • Sillapawattana P, Schäffer A (2016) Effects of imidacloprid on detoxifying enzyme glutathione S-transferase on Folsomia candida (Collembola). Environ Sci Pollut Res Int Apr 20 [Epub ahead of print] PubMed PMID: 27094278

  • Singh P, Prasad SM (2018) Antioxidant enzyme responses to the oxidative stress dueto chlorpyrifos, dimethoate and dieldrin stress in palak (Spinacia oleracea L.) and their toxicity alleviation by soil amendments in tropical croplands. Sci Total Environ 630:839–848

    Article  CAS  Google Scholar 

  • Spiazzi CC, Manfredini V, Barcellos da Silva FE, Flores ÉMM, Izaguirry AP, Vargas LM, Soares MB, Santos FW (2013) γ-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes. Food Chem Toxicol 55:526–532

    Article  CAS  Google Scholar 

  • Torres-Manzo AP, Franco-Colín M, Blas-Valdivia V, Pineda-Reynoso M, Cano-Europa E (2018) Hypothyroidism causes endoplasmic reticulum stress in adult rat hippocampus: a mechanism associated with hippocampal damage. Oxidative Med Cell Longev 2018:2089404

    Article  Google Scholar 

  • Vicente-Sanchez C, Egido J, Sanchez-Gonzalez PD et al (2008) Effect of the flavonoid quercetin on cadmium-induced hepatotoxicity. Food Chem Toxicol 46:2279–2287

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Zargar S, Siddiqi NJ, Al Daihan SK, Wani TA (2015) Protective effects of quercetinon cadmium fluoride induced oxidative stress at different intervals of time inmouse liver. Acta Biochim Pol 62:207–213

    Article  CAS  Google Scholar 

  • Zhang MH, Liang ZQ, Qin Q, Li SL, Zhou DS, Tang L (2013) Effects of quercetin on serum levels of resistin and IL-18 and on insulin resistance in non-alcoholic fatty liver disease rats. Zhonghua Gan Zang Bing Za Zhi 21:66–70

    CAS  PubMed  Google Scholar 

  • Zhang R, Zhang N, Zhang H, Liu C, Dong X, Wang X, Zhu Y, Xu C, Liu L, Yang S, Huang S, Chen L (2017) Celastrol prevents cadmium-induced neuronal cell death by blocking reactive oxygen species-mediated mammalian target of rapamycin pathway. Br J Pharmacol 174:82–100

    Article  CAS  Google Scholar 

  • Zhao X, Cheng Z, Zhu YI, Li S, Zhang L, Luo Y (2015) Effects of paternal cadmium exposure on the sperm quality of male rats and the neurobehavioral system of their offspring. Exp Ther Med 10:2356–2360

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sumita Halder.

Ethics declarations

Conflict of interest

There is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Halder, S., Kar, R., Chandra, N. et al. Alteration in cognitive behaviour, brain antioxidant enzyme activity and their gene expression in F1 generation mice, following Cd exposure during the late gestation period: modulation by quercetin. Metab Brain Dis 33, 1935–1943 (2018). https://doi.org/10.1007/s11011-018-0299-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-018-0299-y

Keywords

Navigation