Cordyceps Militaris improves neurite outgrowth in Neuro2A cells and reverses memory impairment in rats

Abstract

The aim of this study was to evaluate the effect of Cordyceps militaris (CM) on neurite outgrowth in Neuro2A mouse neuroblastoma cells and scopolamineinduced learning and memory deficits in rats. Pretreatment with CM (5–20 μg/mL) for 1 h was sufficient to stimulate primary neurite sprouting and extension of Neuro2A cells after 24 h cultivation in a dose-dependent manner. The CM also increased choline acetyltransferase expression in differentiated Neuro2A cells. Administration of CM significantly reversed the scopolamine-induced deficit in memory, and it alleviated decrease in cholinergic immunoreactivity in the hippocampus. Our results demonstrated that in vitro neuritogenesis of Neuro2A cell lines by CM constitutes a potential clue that could help to explain in vivo improvement of memory functions using the behavioral tasks. These results suggest that CM is strongly effective in protecting against memory-related neuronal degeneration in the brain and retarding the progression of memory deficits associated with various neurodegenerative diseases.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Firenzuoli F, Gori L, Lombardo G. The medicinal mushroom Agaricus blazei murrill: Review of literature and pharmacotoxicological problems. Evid.-Based. Compl. Alt. 5: 3–15 (2008)

    Article  CAS  Google Scholar 

  2. 2.

    Guo JY, Han CC, Liu YM. A Contemporary treatment approach to both diabetes and depression by Cordyceps sinensis, rich in vanadium. Evid. -Based. Compl. Alt. 7: 387–389 (2010)

    Article  Google Scholar 

  3. 3.

    Won SY, Park EH. Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris. J. Ethnopharmacol. 96: 555–561 (2005)

    Article  Google Scholar 

  4. 4.

    Cheng Z, He W, Zhou X, Lv Q, Xu X, Yang S, Zhao C, Guo L. Cordycepin protects against cerebral ischemia/reperfusion injury in vivo and in vitro. Eur. J. Pharmacol. 664: 20–28 (2011)

    Article  CAS  Google Scholar 

  5. 5.

    Hasselmo ME. The role of acetylcholine in learning and memory. Curr. Opin. Neurobiol. 16: 710–715 (2006)

    Article  CAS  Google Scholar 

  6. 6.

    Drever BD, Anderson WG, Johnson H, O’Callaghan M, Seo S, Choi DY, Riedel G, Platt B. Memantine acts as a cholinergic stimulant in the mouse hippocampus. J. Alzheimers Dis. 12: 319–333 (2007)

    CAS  Google Scholar 

  7. 7.

    Klinkenberg I, Blokland A. The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies. Neurosci. Biobehav. R. 34: 1307–1350 (2010)

    Article  CAS  Google Scholar 

  8. 8.

    Mohapel P, Leanza G, Kokaia M, Linvall O. Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning. Neurobiol. Aging 36: 939–946 (2005)

    Article  Google Scholar 

  9. 9.

    Ebert U, Kirch W. Scopolamine model of dementia: Electroencephalogram findings and cognitive performance. Eur. J. Clin. Invest. 28: 944–949 (1998)

    Article  CAS  Google Scholar 

  10. 10.

    Evans NA, Facci L, Owen DE, Soden PE, Burbidge SA, Prinjha RK, Richardson JC, Skaper SD. Abeta(1–42) reduces synapse number and inhibits neurite outgrowth in primary cortical and hippocampal neurons: A quantitative analysis. J. Neurosci. Meth. 175: 96–103 (2008)

    Article  CAS  Google Scholar 

  11. 11.

    Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K. Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha. Neuroreport 13: 1715–1720 (2002)

    Article  CAS  Google Scholar 

  12. 12.

    Wang JF, Wei DQ, Chou KC. Drug candidates from traditional chinese medicines. Curr. Top. Med. Chem. 8: 1656–1665 (2008)

    Article  CAS  Google Scholar 

  13. 13.

    Kim HG, Ju MS, Park H, Seo Y, Jang YP, Hong J, Oh MS. Evaluation of Samjunghwan, a traditional medicine, for neuroprotection against damage by amyloid-β in rat cortical neurons. Chem. Biol. Interact. 187: 246–248 (2010)

    Article  Google Scholar 

  14. 14.

    Hara H, Kataoka S, Anan M, Ueda A, Mutoh T, Tabira T. The therapeutic effects of the herbal medicine, Juzen-taiho-to, on amyloid-β burden in a mouse model of Alzheimer’s disease. J. Alzheimers Dis. 20: 427–439 (2010)

    Google Scholar 

  15. 15.

    Shahidi S, Komaki A, Mahmoodi M, Atrvash N, Ghodrati M. Ascorbic acid supplementation could affect passive avoidance learning and memory in rat. Brain Res. Bull. 76: 109–113 (2008)

    Article  CAS  Google Scholar 

  16. 16.

    Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. Academic Press, New York, NY, USA. pp. 54–85 (1986)

    Google Scholar 

  17. 17.

    Markus A, Zhong J, Snider WD. Raf and Akt mediate distinct aspects of sensory axon growth. Neuron 35: 65–76 (2002)

    Article  CAS  Google Scholar 

  18. 18.

    Bonnet E, Touyarot K, Alfos S, Pallet V, Higueret P, Abrous DN. Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin A deprived rats. PLoS. One. 3: e3487 (2008)

    Article  Google Scholar 

  19. 19.

    Lorenzini CA, Baldi E, Bucherelli C, Sacchett B, Tassoni G. Role of dorsal hippocampus in acquisition, consolidation, and retrieval of rat’s passive avoidance response: A tetrodotoxin functional inactivation study. Brain Res. 730: 32–39 (1996)

    Article  CAS  Google Scholar 

  20. 20.

    Lee B, Park J, Kwon S, Park MW, Oh SM, Yeom MJ, Shim I, Lee HJ, Hahm DH. Effect of wild ginseng on scopolamine-induced acetylcholine depletion in the rat hippocampus. J. Pharm. Pharmacol. 62: 263–271 (2010)

    Article  CAS  Google Scholar 

  21. 21.

    Iwase T, Ojika K, Matsukawa N, Nishino H, Yamamoto T, Okada H, Fujimori O, Ueda R. Muscarinic cholinergic and glutamatergic reciprocal regulation of expression of hippocampal cholinergic neurostimulating peptide precursor protein gene in rat hippocampus. Neuroscience 102: 341–352 (2001)

    Article  CAS  Google Scholar 

  22. 22.

    Ohara T, Tanaka K, Fukaya H, Demura N, Iimura A, Seno N. SDZ ENA 713 facilitates central cholinergic function and ameliorates spatial memory impairment in rats. Behav. Brain Res. 83: 229–233 (1997)

    Article  CAS  Google Scholar 

  23. 23.

    Cheng LL, Chen XN, Wang Y, Yu L, Kuang X, Wang LL, Yang W, Du JR. Z-ligustilide isolated from Radix Angelicae sinensis ameliorates the memory impairment induced by scopolamine in mice. Fitoterapia 82: 1128–1132 (2011)

    Article  CAS  Google Scholar 

  24. 24.

    Oh JH, Choi BJ, Chang MS, Park SK. Nelumbo nucifera semen extract improves memory in rats with scopolamine-induced amnesia through the induction of choline acetyltransferase expression. Neurosci. Lett. 461: 41–44 (2009)

    Article  CAS  Google Scholar 

  25. 25.

    Giacobini E. Long term stabilizing effect of cholinesterase inhibitors in the therapy of Alzheimer’s disease. J. Neur. Tr. S. 62: 181–187 (2002)

    CAS  Google Scholar 

  26. 26.

    Abrous DN, Koehl M, Le Moal M. Adult neurogenesis: From precursors to network and physiology. Physiol. Rev. 85: 523–569 (2005)

    Article  CAS  Google Scholar 

  27. 27.

    Leuner B, Gould E, Shors TJ. Is there a link between adult neurogenesis and learning? Hippocampus 16: 216–224 (2006)

    Article  Google Scholar 

  28. 28.

    Zhang CL, Zou Y, He W, Gage FH, Evans RM. A role for adult TLXpositive neural stem cells in learning and behaviour. Nature 451: 1004–1007 (2008)

    Article  CAS  Google Scholar 

  29. 29.

    Crandall J, Sakai Y, Zhang J, Koul O, Mineur Y, Crusio WE, McCaffery P. 13-cis-Retinoic acid suppresses hippocampal cell division and hippocampal-dependent learning in mice. P. Natl. Acad. Sci. USA 101: 5111–5116 (2004)

    Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Dae-Hyun Hahm.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lee, B., Park, J., Park, J. et al. Cordyceps Militaris improves neurite outgrowth in Neuro2A cells and reverses memory impairment in rats. Food Sci Biotechnol 20, 1599–1608 (2011). https://doi.org/10.1007/s10068-011-0221-4

Download citation

Keywords

  • memory
  • neurite outgrowth
  • cholinergic system
  • scopolamine
  • Cordyceps militaris