Skip to main content

Advertisement

Log in

Organosulfur compound protects against memory decline induced by scopolamine through modulation of oxidative stress and Na+/K+ ATPase activity in mice

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

Abstract

The present study investigated the possible effect of BMMS in protecting against memory impairment in an Alzheimer’s disease model induced by scopolamine in mice. Another objective was to evaluate the involvement of oxidative stress and Na+/K+ ATPase activity in cerebral cortex and hippocampus of mice. Male Swiss mice were divided into four groups: groups I and III received canola oil (10 ml/kg, intragastrically (i.g.)), while groups II and IV received BMMS (10 mg/kg, i.g.). Thirty minutes after treatments, groups III and IV received scopolamine (1 mg/kg, intraperitoneal (i.p.)), while groups I and II received saline (5 ml/kg, i.p.). Behavioral tests were performed thirty minutes after scopolamine or saline injection. Cerebral cortex and hippocampus were removed to determine the thiobarbituric acid reactive species (TBARS) levels, non-protein thiols (NPSH) content, catalase (CAT) and Na+/K+ ATPase activities. The results showed that BMMS pretreatment protected against the reduction in alternation and latency time induced by scopolamine in the Y-maze test and step-down inhibitory avoidance, respectively. In the Barnes maze, the latency to find the escape box and the number of holes visited were attenuated by BMMS. Locomotor and exploratory activities were similar in all groups. BMMS pretreatment protected against the increase in the TBARS levels, NPSH content and CAT activity, as well as the inhibition on the Na+/K+ ATPase activity caused by scopolamine in the cerebral cortex. In the hippocampus, no significant difference was observed. In conclusion, the present study revealed that BMMS protected against the impairment of retrieval of short-term and long-term memories caused by scopolamine in mice. Moreover, antioxidant effect and protection on the Na+/K+ ATPase activity are involved in the effect of compound against memory impairment in AD model induced by scopolamine.

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
Fig. 9

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  • Agrawal R, Tyagi E, Saxena G, Nath C (2009) Cholinergic influence on memory stages: a study on scopolamine amnesic mice. Indian J Pharm 41:192–196

    Article  Google Scholar 

  • Ali EHA, Arafa NMS (2011) Comparative protective action of curcumin, memantine and diclofenac against scopolamine-induced memory dysfunction. Fitoterapia 82:601–608

    Article  CAS  PubMed  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principles of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Dawson GR, Heyes CM, Iversen SD (1992) Pharmacological mechanisms and animal models of cognition. Behav Pharmacol 3:285–297

    Article  CAS  PubMed  Google Scholar 

  • Dickey CA, Gordon MN, Wilcock DM, Herber DL, Freeman MJ, Morgan D (2005) Dysregulation of Na+/K+−ATPase by amyloid in APP+PS1 transgenic mice. BMC Neurosci 2:6–7

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Fiske CH, Subbarow YJ (1925) The calorimetic determination of phosphorus. Biol Chem 66:375–381

    CAS  Google Scholar 

  • Francis PT, Palmer AM, Snape M, Wilcock GK (1999) The cholinergic hypothesis of Alzheimer's disease: a review of progress. J Neurol Neurosurg Psychiatry 66:137–147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giacobini E (2003) Cholinesterases: new roles in brain functionin Alzheimer’s disease. Neurochem Res 28:515–522

    Article  CAS  PubMed  Google Scholar 

  • Hamada K, Matsuura H, Sanada M, Toyoda F, Omatsu-Kanbe M, Kashiwagi A, Yasuda H (2003) Properties of the Na+/K+ pump current in small neurons from adult rat dorsal root ganglia. Br J Pharmacol 138:1517–1527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ianiski FR, Alves CB, Bassaco MM, Silveira CC, Luchese C (2014) Protective effect of ((4-tert-butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide, a novel unsymmetrical divinyl sulfide, on an oxidative stress model induced by sodium nitroprusside in mouse brain: involvement of glutathione peroxidase activity. J Pharm Pharmacol 66:1747–1754

    Article  CAS  PubMed  Google Scholar 

  • Ito K, Ahadieh S, Corrigan B, French J, Fullerton T, Tensfeldt T (2010) Disease progression meta-analysis model in Alzheimer’s disease. Alzheimers Dement 6:39–53

    Article  CAS  PubMed  Google Scholar 

  • Izquierdo I, McGaugh JL (2000) Behavioural pharmacology and its contribution to the molecular basis of memory consolidation. Behav Pharmacol 11:517–534

    Article  CAS  PubMed  Google Scholar 

  • Izquierdo I, Medina JH (1998) On brain lesions, the milkman and Sigmunda. Trends Neurosci 21:421–424

    Article  Google Scholar 

  • Izquierdo I, Barros DM, Mello e Souza T, de Souza MM, Izquierdo LA, Medina JH (1998) Mechanisms for memory types differ. Nature 393:635–636

    Article  CAS  PubMed  Google Scholar 

  • Kim MJ, Choi SJ, Lim ST, Kim HK, Kim YJ, Yoon HG, Shin DH (2008) Zeatin supplement improves scopolamine-induced memory impairment in mice. Biosci Biotechnol Biochem 72:577–581

    Article  CAS  PubMed  Google Scholar 

  • Konar A, Shah N, Singh R, Saxena N, Kaul SC, Wadhwa R, Thakur MK (2011) Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells. PLoS One 6:e27265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar AR, Kurup PA (2002) Inhibition of membrane Na+−K+ ATPase activity: a common pathway in central nervous system disorders. J Assoc Physicians India 50:400–406

    CAS  PubMed  Google Scholar 

  • Kumar A, Singh A, Ekavali (2015) A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacol Rep 67:195–203

    Article  CAS  PubMed  Google Scholar 

  • Lii CK, Liu KL, Cheng YP, Lin AH, Chen HW, Tsai CW (2010) Sulforaphane and alpha-lipoic acid upregulate the expression of the pi class of glutathione S-transferase through c-Jun and Nrf2 activation. J Nutr 140:885–892

    Article  CAS  PubMed  Google Scholar 

  • Lochner M, Thompson AJ (2016) The muscarinic antagosnists scopolamine and atropine are comparative antagonists at 5-HT3 receptors. Neuropharmacology 108:220–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo Z, Sheng J, Sun Y, Lu C, Yan J, Liu A, Luo HB, Huang L, Li X (2013) Synthesis and evaluation of multi-target-directed ligands against Alzheimer's disease based on the fusion of donepezil and ebselen. J Med Chem 56:9089–9099

    Article  CAS  PubMed  Google Scholar 

  • Murugavel L, Pari L (2007) Effects of diallyl tetrasulfide on cadmium induced oxidative damage in the liver of rats. Hum Exp Toxicol 26:527–534

    Article  CAS  PubMed  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  PubMed  Google Scholar 

  • Pinto JT, Rivlin RS (2001) Antiproliferative effects of allium derivatives from garlic. J Nutr 131:1058–1060

    Google Scholar 

  • Pinton S, da Rocha JT, Zeni G, Nogueira CW (2010) Organoselenium improves memory decline in mice: involvement of acetylcholinesterase activity. Neurosci Lett 472:56–60

    Article  CAS  PubMed  Google Scholar 

  • Pompl PN, Mullan MJ, Bjugstad K, Arendash GW (1999) Adaptation of the circular platform spatial memory task for mice: use in detecting cognitive impairment in the APPsw transgenic mouse model for Alzheimer’s disease. J Neurosci Methods 87:87–95

    Article  CAS  PubMed  Google Scholar 

  • Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaalysis. Alzheimers Dement 9:63–75

    Article  PubMed  Google Scholar 

  • Sakaguchi M, Koseki M, Wakamatsu M, Matsumura E (2006) Effects of systemic administration of beta-casomorphin-5 on learning and memory in mice. Eur J Pharmacol 530:81–87

    Article  CAS  PubMed  Google Scholar 

  • Sarter M, Bodewitz G, Stephens DN (1988) Attenuation of scopolamine induced impairment of spontaneous alternation behavior by antagonist but not inverse agonist and b-carboline. Psychopharmacol 94:491–495

    Article  CAS  Google Scholar 

  • Shaik IH, George JM, Thekkumkara TJ, Mehvar R (2008) Protective effects of diallyl sulfide, a garlic constituent, on the warm hepatic ischemia-reperfusion injury in a rat model. Pharm Res 25:2231–2242

    Article  CAS  PubMed  Google Scholar 

  • Silveira CC, Rinaldi F, Bassaco MM, Guadagnin RC, Kaufman TS (2011) Synthesis of (diphenylphosphinoyl)methyl vinyl sulfides, symmetric and asymmetric divinyl sulfides from bis[(diphenylphosphinoyl)methyl] sulfide. Synthesis 8:1233–1242

    Article  Google Scholar 

  • Souza ACG, Brüning CA, Leite MR, Zeni G, Nogueira CW (2010) Diphenyl diselenide improves scopolamine-induced memory impairment in mice. Behav Pharmacol 21:556–562

    Article  CAS  PubMed  Google Scholar 

  • Sweadner KJ (1992) Overlapping and diverse distribution of Na+/K+-ATPase isozymes in neurons and glia. Can J Physiol Pharmacol 70:S255–S259

    Article  CAS  PubMed  Google Scholar 

  • Tota S, Hanif K, Kamat PK, Najmi AK, Nath C (2012) Role of central angiotensin receptors in scopolamine-induced impairment in memory, cerebral blood flow, and cholinergic function. Psychopharmacology 222:185–202

    Article  CAS  PubMed  Google Scholar 

  • Walsh RN, Cummins RA (1976) The open-field test: a critical review. Psychol Bull 83:482–504

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Wang XL, Liu HR, Rose P, Zhu YZ (2010) Protective effects of cysteine analogues on acute myocardial ischemia: novel modulators of endogenous H2S production. Antioxid Redox Signal 12:1155–1165

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Wang Y, Li W, Mao F, Sun Y, Huang L, Li X (2014) Design, synthesis and evaluation of multitarget-direct selenium- containing clioquinol derivates for the treatment of Alzheimer’s disease. ACS Chem Neurosci 5:952–962

    Article  CAS  PubMed  Google Scholar 

  • Weon JB, Jung YS, Je Ma C (2016) Cognitive-enhancing effect of Dianthus superbus Var. Longicalycinus on scopolamine-induced memory impairment in mice. Biomol Ther 24:298–304

    Article  CAS  Google Scholar 

  • Yi L, Su Q (2013) Molecular mechanisms for the anti-cancer effects of diallyl disulfide. Food Chem Toxicol 57:362–370

    Article  CAS  PubMed  Google Scholar 

  • Zeng TAO, Guo FF, Zhang CL, Zhao S, Dou EE, Gao XC, Xie KQ (2008) The anti-fatty liver effects of garlic oil on acute ethanol-exposed mice. Chem Biol Interact 176:234–232

    Article  CAS  PubMed  Google Scholar 

  • Zhang CL, Zeng T, Zhao XL, Yu LH, Zhu ZP, Xie KQ (2012) Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats. Int J Biol Sci 8:363–374

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang LN, Sun YJ, Pan S, Li JX, Qu YE, Li Y, Wang YL, Gao ZB (2013) Na+-K+-ATPase, a potent neuroprotective modulator against Alzheimer disease. Fundam Clin Pharmacol 27:96–103

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge UFPel, UNIFRA, FAPERGS (research grants #16/2551-0000526-5 – PRONUPEQ and # 10/0005-1 – PRONEX), CAPES and CNPq for the financial support. C.C.S, C.R.J. and C.L. are recipients of CNPq fellowship. M.P.P. is recipients of CAPES fellowship.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Ethel A. Wilhelm or Cristiane Luchese.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (number 007/2011).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Silva, F.D., Pinz, M.P., de Oliveira, R.L. et al. Organosulfur compound protects against memory decline induced by scopolamine through modulation of oxidative stress and Na+/K+ ATPase activity in mice. Metab Brain Dis 32, 1819–1828 (2017). https://doi.org/10.1007/s11011-017-0067-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-017-0067-4

Keywords

Navigation