Biological Trace Element Research

, Volume 189, Issue 1, pp 180–185 | Cite as

Zinc-Enriched Yeast Improves Learning and Memory Impairments in Zinc-Deficient Rats

  • Shuang-Qing ZhangEmail author
  • Hai-Bo Zhang
  • Qian Cheng
  • Ya-Min Zhu
  • Chang-Hong Xia
  • Yin-Hong Zhu
  • Yan ZhangEmail author


Zinc (Zn) highly concentrates in the brain and plays a key role in memory formation and learning processes. Zn deficiency results in cognitive impairments, memory deficits, alterations of neuropsychological behavior, and motor development. Although Zn-enriched yeast (ZnY) is widely used for dietary fortification and supplementation of Zn, the effect of ZnY on cognition still remains unclear. The purpose of the study was to investigate the effect of ZnY on behavior in Zn-deficient and Zn-sufficient rats. Three-week-old rats were fed low Zn diets for 145 days to establish Zn-deficient rats. ZnY was orally administered to Zn-deficient rats at three dose levels of 1, 2, and 4 mg Zn/kg/day for 55 days. Rat appearance, body weight, plasma and brain Zn, Morris water maze test, and step-through passive avoidance test were observed. Compared to Zn-sufficient rats, body weight gain, plasma zinc level, resident time, and step-through time in Zn-deficient rats were significantly lower. Zn deficiency impaired functions of learning and memory, while ZnY as a plausible therapeutic intervention alleviated the cognitive impairments caused by Zn deficiency.


Zinc-enriched yeast Learning Memory Zinc deficiency 


Funding Information

The work was financially supported by the Hubei Provincial Natural Science Foundation of China (grant numbers 2017CFB572, 2018CFB612).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Statement of informed consent

All procedures were performed according to the Guide for the Care and Use of Laboratory Animals (NIH publication no. 85–23, eighth edition in 2011) and were approved by our Institutional Animal Care and Use Committee.


  1. 1.
    Yang Y, Jing XP, Zhang SP, Gu RX, Tang FX, Wang XL, Xiong Y, Qiu M, Sun XY, Ke D, Wang JZ, Liu R (2013) High dose zinc supplementation induces hippocampal zinc deficiency and memory impairment with inhibition of BDNF signaling. PLoS One 8(1):e55384. CrossRefGoogle Scholar
  2. 2.
    Maret W, Sandstead HH (2006) Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol 20(1):3–18. CrossRefGoogle Scholar
  3. 3.
    Lowe N (2016) Assessing zinc in humans. Curr Opin Clin Nutr Metab Care 19:321–327CrossRefGoogle Scholar
  4. 4.
    Prasad AS (2014) Impact of the discovery of human zinc deficiency on health. J Trace Elem Med Biol 28(4):357–363. CrossRefGoogle Scholar
  5. 5.
    Flinn JM, Hunter D, Linkous DH, Lanzirotti A, Smith LN, Brightwell J, Jones BF (2005) Enhanced zinc consumption causes memory deficits and increased brain levels of zinc. Physiol Behav 83(5):793–803. CrossRefGoogle Scholar
  6. 6.
    Turner TY, Soliman MR (2000) Effects of zinc on spatial reference memory and brain dopamine (D1) receptor binding kinetics in rats. Prog Neuro-Psychopharmacol Biol Psychiatry 24(7):1203–1217CrossRefGoogle Scholar
  7. 7.
    Hamadani JD, Fuchs GJ, Osendarp SJ, Huda SN, Grantham-McGregor SM (2002) Zinc supplementation during pregnancy and effects on mental development and behaviour of infants: a follow-up study. Lancet 360(9329):290–294. CrossRefGoogle Scholar
  8. 8.
    Halas ES, Hunt CD, Eberhardt MJ (1986) Learning and memory disabilities in young adult rats from mildly zinc deficient dams. Physiol Behav 37(3):451–458CrossRefGoogle Scholar
  9. 9.
    Bhatnagar S, Taneja S (2001) Zinc and cognitive development. Br J Nutr 85(Suppl 2):S139–S145CrossRefGoogle Scholar
  10. 10.
    Gao HL, Xu H, Xin N, Zheng W, Chi ZH, Wang ZY (2011) Disruption of the CaMKII/CREB signaling is associated with zinc deficiency-induced learning and memory impairments. Neurotox Res 19(4):584–591. CrossRefGoogle Scholar
  11. 11.
    Piechal A, Blecharz-Klin K, Pyrzanowska J, Widy-Tyszkiewicz E (2016) Influence of long-term zinc administration on spatial learning and exploratory activity in rats. Biol Trace Elem Res 172(2):408–418. CrossRefGoogle Scholar
  12. 12.
    Caulfield LE, Zavaleta N, Shankar AH, Merialdi M (1998) Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. Am J Clin Nutr 68(2 Suppl):499S–508SCrossRefGoogle Scholar
  13. 13.
    Frederickson CJ (1989) Neurobiology of zinc and zinc-containing neurons. Int Rev Neurobiol 31:145–238CrossRefGoogle Scholar
  14. 14.
    Lu YM, Taverna FA, Tu R, Ackerley CA, Wang YT, Roder J (2000) Endogenous Zn(2+) is required for the induction of long-term potentiation at rat hippocampal mossy fiber-CA3 synapses. Synapse 38(2):187–197.<187::AID-SYN10>3.0.CO;2-R CrossRefGoogle Scholar
  15. 15.
    Li Y, Hough CJ, Frederickson CJ, Sarvey JM (2001) Induction of mossy fiber --> Ca3 long-term potentiation requires translocation of synaptically released Zn2+. J Neurosci 21(20):8015–8025CrossRefGoogle Scholar
  16. 16.
    Guidolin D, Polato P, Venturin G, Zanotti A, Mocchegiani E, Fabris N, Nunzi MG (1992) Correlation between zinc level in hippocampal mossy fibers and spatial memory in aged rats. Ann N Y Acad Sci 673:187–193CrossRefGoogle Scholar
  17. 17.
    Frederickson RE, Frederickson CJ, Danscher G (1990) In situ binding of bouton zinc reversibly disrupts performance on a spatial memory task. Behav Brain Res 38(1):25–33CrossRefGoogle Scholar
  18. 18.
    Vinson JA, Tompkins TA, Agbor GA (2007) Comparative bioavailability of mineral-enriched gluconates and yeast in rat liver after depletion-repletion feeding. Biol Trace Elem Res 118(2):104–110. CrossRefGoogle Scholar
  19. 19.
    Tompkins TA, Renard NE, Kiuchi A (2007) Clinical evaluation of the bioavailability of zinc-enriched yeast and zinc gluconate in healthy volunteers. Biol Trace Elem Res 120(1–3):28–35. CrossRefGoogle Scholar
  20. 20.
    Nitrayova S, Windisch W, von Heimendahl E, Muller A, Bartelt J (2012) Bioavailability of zinc from different sources in pigs. J Anim Sci 90(Suppl 4):185–187. CrossRefGoogle Scholar
  21. 21.
    Zhang SQ, Yu XF, Zhang HB, Peng N, Chen ZX, Cheng Q, Zhang XL, Cheng SH, Zhang Y (2018) Comparison of the oral absorption, distribution, excretion, and bioavailability of zinc sulfate, zinc gluconate, and zinc-enriched yeast in rats. Mol Nutr Food Res 62(7):e1700981. CrossRefGoogle Scholar
  22. 22.
    Zhang S, Zhang Y, Peng N, Zhang H, Yao J, Li Z, Liu L (2014) Pharmacokinetics and biodistribution of zinc-enriched yeast in rats. Sci World J 2014:217142–217144. Google Scholar
  23. 23.
    Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1(2):848–858. CrossRefGoogle Scholar
  24. 24.
    Suzuki H, Asakawa A, Li J, Tsai M, Amitani H, Ohinata K, Komai M, Inui A (2011) Zinc as an appetite stimulator - the possible role of zinc in the progression of diseases such as cachexia and sarcopenia. Recent Pat Food Nutr Agric 3(3):226–231CrossRefGoogle Scholar
  25. 25.
    Ohinata K, Takemoto M, Kawanago M, Fushimi S, Shirakawa H, Goto T, Asakawa A, Komai M (2009) Orally administered zinc increases food intake via vagal stimulation in rats. J Nutr 139(3):611–616. CrossRefGoogle Scholar
  26. 26.
    Contestabile A, Pena-Altamira E, Virgili M, Monti B (2016) Zinc supplementation in rats impairs hippocampal-dependent memory consolidation and dampens post-traumatic recollection of stressful event. Eur Neuropsychopharmacol 26(6):1070–1082. CrossRefGoogle Scholar
  27. 27.
    Sandusky-Beltran LA, Manchester BL, McNay EC (2017) Supplementation with zinc in rats enhances memory and reverses an age-dependent increase in plasma copper. Behav Brain Res 333:179–183. CrossRefGoogle Scholar
  28. 28.
    Nowak G, Szewczyk B, Wieronska JM, Branski P, Palucha A, Pilc A, Sadlik K, Piekoszewski W (2003) Antidepressant-like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats. Brain Res Bull 61(2):159–164CrossRefGoogle Scholar
  29. 29.
    Piechal A, Blecharz-Klin K, Pyrzanowska J, Widy-Tyszkiewicz E (2012) Maternal zinc supplementation improves spatial memory in rat pups. Biol Trace Elem Res 147(1–3):299–308. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.National Institute for Nutrition and HealthChinese Center for Disease Control and PreventionBeijingChina
  2. 2.The Hubei Provincial Key Laboratory of Yeast FunctionYichangChina

Personalised recommendations