Skip to main content
Log in

The Toxic Effect of Lithium Ion on Neurons (PC12 cells) and Aβ42 Molecules

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

In this study, the neurotoxicity of Li ion and its effect on the morphologies of Aβ42 molecules were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, fluorescence (FL), atomic force microscopy (AFM), and circular dichroism (CD) spectroscopy. MTT assays show that Li ion with a dosage level lower than 50 mg/l did not show detectable cytotoxicity on pheochromocytoma (PC12) cells whereas a dosage level higher than 100 mg/l resulted in significant cytotoxicity. The interaction between Aβ42 and Li ion occurs, and the quenching effect of Li ion on the fluorescence emission of AΒ42 is found to be concentration dependent, suggesting that Li ion can bind to the Aβ42 molecules. CD results suggest that a more incompact conformation state will be adopted upon the interaction between Aβ42 and Li ion. According to AFM images, Li ion could induce the formation of the fibrils after incubation for 3 or 5 days. The formation of the oligomer and fibrils originates from the strong interactions between Aβ42 and Li ion. Li ion could accelerate the random coil Aβ42 monomers aggregating into the β-sheet fibrils, which would induce the neurotoxic effect.

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.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Coppen A (1999) Editorial—50 years of lithium treatment of mood disorders. Bipolar Disord 1:3–4

    Article  CAS  PubMed  Google Scholar 

  2. Del Grande C, Musetti L, Marazziti D, Muti M, Corsini GU, Dell'Osso L (2013) Lithium monotherapy versus lithium and valproate in manic and mixed states: correlation between serum lithium levels and treatment response. Eur Neuropsychopharmacol 23(2):375

    Article  Google Scholar 

  3. Maj M (2004) The impact of lithium prophylaxis on the course of bipolar disorder: a review of the research evidence. Bipolar Disord 2:93–101

    Article  Google Scholar 

  4. Lakshmi N, Konstantinos N, Rahman Z et al (2013) Efficacy of aripiprazole versus placebo as adjuncts to lithium or valproate in relapse prevention of manic or mixed episodes in bipolar I patients stratified by index manic or mixed episode. J Affect Disord 147:365–372

    Article  Google Scholar 

  5. Lin YF, Huang MC, Liu HC (2013) Glycogen synthase kinase 3β gene polymorphisms may be associated with bipolar I disorder and the therapeutic response to lithium. J Affect Disord 147:401–406

    Article  CAS  PubMed  Google Scholar 

  6. Soares JC, Gershon S (1998) The lithium ion: a foundation for psychopharmacological specificity. Neuropsychopharmacology 19:167–182

    Article  CAS  PubMed  Google Scholar 

  7. Hanson ND, Nemeroff CB, Owens MJ (2011) Lithium, but not fluoxetine or the corticotropin-releasing factor receptor 1 receptor antagonist r121919, increases cell proliferation in the adult dentate gyrus. J Pharmacol Exp Ther 337:180–186

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Renshaw PF, Wicklund S (1988) In vivo measurement of lithium in humans by nuclear magnetic spectroscopy. Biol Psychiatry 23:465–475

    Article  CAS  PubMed  Google Scholar 

  9. Komoroski RA, Newton JEO, Walker E et al (1990) In vivo NMR spectroscopy of lithium-7 in humans. Magn Reson Med 16:347–356

    Article  Google Scholar 

  10. Kato T, Takahashi S, Inubushi T (1992) Brain lithium concentration by 7Li- and 1H-mangetic resonance spectroscopy in bipolar disorder. Psychiatr Res-Neuroim 45:53–63

    Article  CAS  Google Scholar 

  11. Barnham KJ, Smith DG, Cappai R (2007) The redox chemistry of the Alzheimer's disease amyloid beta peptide. BBA-Biomembranes 1768:1976–1990

    Article  PubMed  Google Scholar 

  12. Pike CJ, Walencewicz AJ, Glabe CG, Cotman CW (1991) In vitro aging of beta-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res 563:311–314

    Article  CAS  PubMed  Google Scholar 

  13. Anne M, Justin A, Nicholas S, David R (2014) Simulations of monomeric amyloid β-peptide (1–40) with varying solution conditions and oxidation state of Met35: implications for aggregation. Arch Biochem Biophys 545:44–52

    Article  Google Scholar 

  14. Biancalana M, Koide S (2010) Molecular mechanism of thioflavin-T binding to amyloid fibrils. BBA-Proteins Proteom 1804:1405–1412

    Article  CAS  Google Scholar 

  15. Krebs MRH, Bromley EHC, Donald AM (2005) The binding of thioflavin-T to amyloid fibrils: localisation and implications. J Struct Biol 149:30–37

    Article  CAS  PubMed  Google Scholar 

  16. Ulrih NP, Barry CH, Fink AL (2008) Impact of Tyr to Ala mutations on alpha-synuclein fibrillation and structural properties. BBA-Mol Basis Dis 1782:581–585

    Article  CAS  Google Scholar 

  17. Miura T, Suzuki K, Kohata N, Takeuchi H (2000) Metal binding modes of Alzheimer's amyloid beta-peptide in insoluble aggregates and soluble complexes. Biochemistry-Us 39:7024–7031

    Article  CAS  Google Scholar 

  18. Zatta P, Ricchelli F, Drago D, Filippi B, Tognon G (2005) Aluminum-triggered structural modifications and aggregation of beta-amyloids. Cell Mol Life Sci 62:1724–1733

    Article  PubMed  Google Scholar 

  19. Jiang T, Wang L, Zhang S, Sun PC, Ding CF, Chu YQ, Ping Z (2011) Interaction of curcumin with Al(III) and its complex structures based on experiments and theoretical calculations. J Mol Struct 1004:163–173

    Article  CAS  Google Scholar 

  20. Akitt JW, Gessner W (1984) Aluminum-27 nuclear magnetic resonance investigations of highly alkaline aluminate solutions. J Chem Soc Dalton 147–148

  21. Drago D, Bettella M, Bolognin S, Cendron L, Scancar J, Milacic R, Ricchelli F, Casini A, Messori L, Tognon G, Zatta P (2008) Potential pathogenic role of beta-amyloid(1–42)-aluminum complex in Alzheimer's disease. Int J Biochem Cell Biol 40:731–746

    Article  CAS  PubMed  Google Scholar 

  22. Besseling NAM, Lyklema J (1997) Molecular thermodynamics of hydrophobic hydration. J Phys Chem B 101:7604–7611

    Article  CAS  Google Scholar 

Download references

Acknowledgment

We gratefully acknowledge the financial support of the National Key Technology Support Program (2009CAI37B01).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Liu Jintong or Pan Fang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, W., Yan, Z., Hongjing, Z. et al. The Toxic Effect of Lithium Ion on Neurons (PC12 cells) and Aβ42 Molecules. Biol Trace Elem Res 159, 410–415 (2014). https://doi.org/10.1007/s12011-014-9949-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-9949-z

Keywords

Navigation