Skip to main content
Log in

Possible Role of Oxidative Stress and Brain Derived Neurotrophic Factor in Triazophos Induced Cognitive Impairment in Rats

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

Abstract

Triazophos, O,O-diethyl-1-H-1,2,4-triazol-3-yl phosphorothioate, (TZ) is an organophosphate pesticide widely used as an insecticide in agriculture fields, however, its adverse effects on cognitive function remain unknown till date. The present study was designed to identify the effect of TZ on cognitive function in order to gain an insight into the molecular mechanism(s) probably involved in TZ induced toxicity. Wistar male albino rats were orally administered with TZ at 8.2 mg/kg bw daily for 30 days. Cognitive function was assessed by evaluating step down latency (SDL) in passive avoidance apparatus, transfer latency (TL) on elevated plus maze and escape latency (EL) using morris water maze. The biochemical changes, in terms of malondialdehyde (MDA), reduced glutathione (GSH) and brain derived neurotrophic factor (BDNF) levels were evaluated in hippocampi regions. Relative mRNA expression and protein expression of BDNF were also evaluated. The results demonstrated that rats treated with TZ showed significantly (p < 0.01) reduced SDL and prolonged TL and EL as compared to control group rats. Moreover, significantly low (p < 0.01) mRNA expression and protein levels (p < 0.001) of BDNF, increased MDA and reduced GSH levels were observed in TZ treated rats. The study concludes that chronic exposure to TZ significantly impairs the learning and memory which may be attributed to the significantly reduced mRNA and protein expression of BDNF in hippocampus. Moreover, BDNF is negatively correlated to MDA levels and positively correlated to GSH levels. Hence, it can be suggested that interplay between BDNF and oxidative stress plays an important role in mediating the toxic effects of TZ.

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
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

TZ:

Triazophos

BDNF:

Brain derived neurotrophic factor

GSH:

Reduced glutathione

MDA:

Malondialdehyde

SDL:

Step down latency

TL:

Transfer latency

EL:

Escape latency

MWM:

Morris water maze

References

  1. Alonso M, Bekinschtein P, Cammarota M, Vianna MRM, Izquierdo I, Medina JH (2005) Endogenous BDNF is required for long-term memory formation in the rat parietal cortex. Learn Mem 12:504–510

    Article  PubMed  Google Scholar 

  2. Amoureux S, Sicard P, Korandji C, Borey A, Benkhadra S, Le Grand AS, Vergely C, Girard C, Rochette L (2008) Increase in levels of BDNF is associated with inflammation and oxidative stress during cardiopulmonary bypass. Int J Biomed Sci 4:204–211

    PubMed  CAS  Google Scholar 

  3. Bekinschtein P, Cammarota M, Igaz LM, Bevilaqua LR, Izquierdo I, Medina JH (2007) Persistence of long-term memory storage requires a late protein synthesis- and BDNF dependent phase in the hippocampus. Neuron 53:261–277

    Article  PubMed  CAS  Google Scholar 

  4. Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH (2008) BDNF is essential to promote persistence of long-term memory storage. PNAS 105:2711–2716

    Article  PubMed  CAS  Google Scholar 

  5. Boutahar N, Reynaud E, Lassabliere F, Brog J (2010) Brain derived neurotrophic factor inhibits cell cycle re-entry but not endoplasmic reticulum stress in cultured neurons following oxidative or excitotoxic stress. J Neurosci Res 88:2263–2271

    Article  PubMed  CAS  Google Scholar 

  6. Bradford MM (1976) A dye binding assay for protein. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  7. Bushnell PJ, Kelly KL, Ward TR (1994) Repeated inhibition of cholinesterase by chlorpyrifos in rats: behavioral neurochemical, and pharmacological indices of tolerance. J Pharmacol Exp Ther 270:15–25

    PubMed  CAS  Google Scholar 

  8. Bushnell PJ, Moser VC, Samsam TE (2001) Comparing cognitive, and screening test for neurotoxicity effects of acute chlorpyrifos on visual signal detection, and a neurobehavioral test battery in rats. Neurotoxicol Teratol 23:33–44

    Article  PubMed  CAS  Google Scholar 

  9. Bushnell PJ, Padilla SS, Ward T, Pope CN, Olszyk VB (1991) Behavioral and neurochemical changes in rats dosed repeatedly with diisopropylfluorophos-phate. J Pharmacol Exp Ther 256:741–750

    PubMed  CAS  Google Scholar 

  10. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:152–159

    Article  Google Scholar 

  11. Donovan MJ, Lin MI, Wiegn P, Ringstedt T, Kraemer R et al (2000) Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization. Development 127:4531–4540

    PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Ernfors P, Lee KF, Jaenisch R (1994) Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature 368:147–150

    Article  PubMed  CAS  Google Scholar 

  14. Hofer M, Pagliusi SR, Hohn A, Leibrock J, Barde Y-A (1990) Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J 9:2459–2464

    PubMed  CAS  Google Scholar 

  15. Itoh J, Nabeshima T, Kameyama T (1990) Utility of an elevated plus-maze for the evaluation of memory in mice: effect of nootropics, scopolamine and electroconvulsive shock. Psychopharmacology 101:27–33

    Article  PubMed  CAS  Google Scholar 

  16. Izquierdo I, Fin C, Schmitz PK, Da Silva RC, Jerusalinsky D, Quillfeldt JA, Ferreira MB, Medina JH, Bazan NG (1995) Memory enhancement by intrahippocampal, intraamygdala, orintraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance task. Proc Natl Acad Sci USA 92:5047–5051

    Article  PubMed  CAS  Google Scholar 

  17. Jain S, Ahmed RS, Arora VK, Banerjee BD (2011) Biochemical and histopathological studies to assess chronic toxicity of Triazophos in blood, liver and brain tissue of rats. Pestic Biochem Phys 100:182–186

    Article  CAS  Google Scholar 

  18. Jain S, Subramaneyaan M, Ahmed RS, Arora VK, Banerjee BD (2010) Induction of oxidative stress and histopathological changes by sub-chronic doses of Triazophos. Indian J Biochem Biophys 47:388–392

    PubMed  CAS  Google Scholar 

  19. Kapczinski F, Frey BN, Andreazza AC, Kauer-Sant’Anna M, Cunha AB, Post RM (2008) Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes. Rev Bras Psiquiatr 30:243–245

    Article  PubMed  Google Scholar 

  20. Kumar M, Kumar A (2007) Report on application and health effects of pesticides commonly used in India. Centre for Science and Environment, New Delhi

    Google Scholar 

  21. Lee B, Cao R, Choi YS, Cho HY, Rhee AD, Hah CK, Hoyt KR, Obrietan K (2009) The CREB/CRE transcriptional pathway: protection against oxidative stress-mediated neuronal cell death. J Neurochem 108:1251–1265

    Article  PubMed  CAS  Google Scholar 

  22. Linnarsson S, Bjorklund A, Ernfors P (1997) Learning deficit in BDNF mutant mice. Eur J Neurosci 9:2581–2587

    Article  PubMed  CAS  Google Scholar 

  23. Livak KJ, Schimittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  24. López-Granero C, Cañadas F, Cardona D, Yu Y, Giménez E, Lozano R, Avila DS, Aschner M, Sánchez-Santed F (2013) Chlorpyrifos-, diisopropylphosphorofluoridate-, and parathion-induced behavioral and oxidative stress effects: are they mediated by analogous mechanisms of action? Toxicol Sci 131:206–216

    Article  PubMed  Google Scholar 

  25. Lyons WE, Mamounas LA, Ricaurte GA, Coppola V, Reid SW, Bora SH, Wihler C, Koliatsos VE, Tessarollo L (1999) Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci USA 96:15239–15244

    Article  PubMed  CAS  Google Scholar 

  26. Mandodari C, Hehgerer B, Ducret T, Borkowoski J (1994) Delayed emergence of effects of memory enhancing drugs: implications for the dynamics of long term memory. Proct Natl Acad Sci 91:2041–2045

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  28. Musazzi L, Cattaneo A, Tardito D, Barbon A, Gennarelli M, Barlati S, Racagni G, Popoli M (2009) Early raise in BDNF in hippocampus suggests induction of posttranscriptional mechanisms by antidepressants. BMC Neurosci 10:48. doi:10.1186/1471-2202-10-48

    Article  PubMed  Google Scholar 

  29. Narayanan SN, Kumar RS, Potu BK, Nayak S, Mailankot M (2009) Spatial memory performance of Wistar rats exposed to mobile phones. Clinics 64:231–234

    Article  PubMed  Google Scholar 

  30. Numakawa T, Matsumoto T, Numakawa Y, Richards M, Yamawaki S, Kunugi H (2011) Protective action of neurotrophic factors and estrogen against oxidative stress-mediated neurodegeneration. J Toxicol 2011:405194. doi:10.1155/2011/405194

    PubMed  Google Scholar 

  31. OECD (2007) Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals 407: repeated dose 28-day oral toxicity study in rodents

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

    Article  PubMed  CAS  Google Scholar 

  33. Patterson SL, Abel T, Deuel TAS, Martin KC, Rose JC, Kandel ER (1996) Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron 16:1137–1145

    Article  PubMed  CAS  Google Scholar 

  34. Rani S, Madan VK, Kathpal TS (2001) Persistence and dissipation behavior of triazophos in canal water under Indian climatic conditions. Ecotoxicol Environ Safety 50:82–84

    Article  PubMed  CAS  Google Scholar 

  35. Salehi I, Farajnia S, Mohammadi M, Ghannad MS (2010) The pattern of brain-derived neurotrophic factor gene expression in the hippocampus of diabetic rats. Iran J Basic Med Sci 13:146–153

    CAS  Google Scholar 

  36. Singh M, Rishi S (2005) Plasma acetylcholinesterase as a biomarker of Triazophos neurotoxicity in young and adult rats. Environ Toxicol Pharmacol 19:471–476

    Article  PubMed  CAS  Google Scholar 

  37. Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jäger S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, Spiegelman BM (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127:397–408

    Article  Google Scholar 

  38. Wang X, Bu HF, De Plaen IG, Tan XD (2009) Milk fat globule-EGF factor 8 mRNA expression in rat splanchnic tissues during postnatal development. Int J Clin Exp Med 2:36–40

    PubMed  CAS  Google Scholar 

  39. Wu A, Ying Z, Gomez-Pinilla F (2004) The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition. Eur J Neurosci 19:1699–1707

    Article  PubMed  Google Scholar 

  40. Yamamoto H, Gurney ME (1990) Human platelets contain brain derived neurotrophic factor. J Neurosci 10:3469–3478

    PubMed  CAS  Google Scholar 

  41. Zou J, Crews F (2006) CREB and NF-kappa B transcription factors regulate sensitivity to excitotoxic and oxidative stress induced neuronal cell death. Cell Mol Neurobiol 26:385–405

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

One of the authors ‘Ms Smita Jain’ is grateful to Council of Scientific and Industrial Research (CSIR) for awarding financial support as Senior Research Fellowship. The authors acknowledge Dr. Mohit Mehndiratta, Assistant Professor, Department of Biochemistry, UCMS for providing help and support during utilization of Real Time PCR system.

Conflict of interest

None declared.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Basu Dev Banerjee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jain, S., Banerjee, B.D., Ahmed, R.S. et al. Possible Role of Oxidative Stress and Brain Derived Neurotrophic Factor in Triazophos Induced Cognitive Impairment in Rats. Neurochem Res 38, 2136–2147 (2013). https://doi.org/10.1007/s11064-013-1122-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-013-1122-0

Keywords

Navigation