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Salvia miltiorrhiza Bunge Blocks Ethanol-Induced Synaptic Dysfunction through Regulation of NMDA Receptor-Dependent Synaptic Transmission

  • Park, Hye Jin (Department of Medicinal Biotechnology, College of Health Sciences and Institute of Convergence Bio-Health, Dong-A University) ;
  • Lee, Seungheon (Department of Aquatic Biomedical Sciences, School of Marine Biomedical Science, College of Ocean Science, Jeju National University) ;
  • Jung, Ji Wook (Department of Herbal Medicinal Pharmacology, College of Herbal Bio-industry, Daegu Haany University) ;
  • Lee, Young Choon (Department of Medicinal Biotechnology, College of Health Sciences and Institute of Convergence Bio-Health, Dong-A University) ;
  • Choi, Seong-Min (Department of Neurology, Chonnam National University Medical School) ;
  • Kim, Dong Hyun (Department of Medicinal Biotechnology, College of Health Sciences and Institute of Convergence Bio-Health, Dong-A University)
  • Received : 2015.11.24
  • Accepted : 2016.03.23
  • Published : 2016.07.01

Abstract

Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. These blackouts experienced by ethanol consumers may be a major cause of the social problems associated with excess ethanol consumption. However, there is currently no established treatment for preventing these ethanol-induced blackouts. In this study, we tested the ethanol extract of the roots of Salvia miltiorrhiza (SM) for its ability to mitigate ethanol-induced behavioral and synaptic deficits. To test behavioral deficits, an object recognition test was conducted in mouse. In this test, ethanol (1 g/kg, i.p.) impaired object recognition memory, but SM (200 mg/kg) prevented this impairment. To evaluate synaptic deficits, NMDA receptor-mediated excitatory postsynaptic potential (EPSP) and long-term potentiation (LTP) in the mouse hippocampal slices were tested, as they are known to be vulnerable to ethanol and are associated with ethanol-induced amnesia. SM (10 and $100{\mu}g/ml$) significantly ameliorated ethanol-induced long-term potentiation and NMDA receptor-mediated EPSP deficits in the hippocampal slices. Therefore, these results suggest that SM prevents ethanol-induced amnesia by protecting the hippocampus from NMDA receptor-mediated synaptic transmission and synaptic plasticity deficits induced by ethanol.

Keywords

References

  1. Aguayo, L. G. (1990) Ethanol potentiates the GABAA-activated Clcurrent in mouse hippocampal and cortical neurons. Eur. J. Pharmacol. 187, 127-130. https://doi.org/10.1016/0014-2999(90)90349-B
  2. Allan, A. M. and Harris, R. A. (1987) Acute and chronic ethanol treatments alter GABA receptor-operated chloride channels. Pharmacol. Biochem. Behav. 27, 665-670. https://doi.org/10.1016/0091-3057(87)90192-4
  3. Allgaier, C. (2002) Ethanol sensitivity of NMDA receptors. Neurochem. Int. 41, 377-382. https://doi.org/10.1016/S0197-0186(02)00046-3
  4. Alvestad, R. M., Grosshans, D. R., Coultrap, S. J., Nakazawa, T., Yamamoto, T. and Browning, M. D. (2003) Tyrosine dephosphorylation and ethanol inhibition of N-Methyl-D-aspartate receptor function. J. Biol. Chem. 278, 11020-11025. https://doi.org/10.1074/jbc.M210167200
  5. Castillo, P. E., Weisskopf, M. G. and Nicoll, R. A. (1994) The role of $Ca^{2+}$ channels in hippocampal mossy fiber synaptic transmission and long-term potentiation. Neuron 12, 261-269. https://doi.org/10.1016/0896-6273(94)90269-0
  6. Chandler, L. J. (2003) Ethanol and brain plasticity: receptors and molecular networks of the postsynaptic density as targets of ethanol. Pharmacol. Ther. 99, 311-326. https://doi.org/10.1016/S0163-7258(03)00096-2
  7. Cheng, T. O. (2007) Cardiovascular effects of Danshen. Int. J. Cardiol. 121, 9-22. https://doi.org/10.1016/j.ijcard.2007.01.004
  8. Dodd, P. R., Beckmann, A. M., Davidson, M. S. and Wilce, P. A. (2000) Glutamate-mediated transmission, alcohol, and alcoholism. Neurochem. Int. 37, 509-533. https://doi.org/10.1016/S0197-0186(00)00061-9
  9. Gulick, D. and Gould, T. J. (2009) Effects of ethanol and caffeine on behavior in C57BL/6 mice in the plus-maze discriminative avoidance task. Behav. Neurosci. 123, 1271-1278. https://doi.org/10.1037/a0017610
  10. Han, Y. M., Oh, H., Na, M., Kim, B. S., Oh, W. K., Kim, B. Y., Jeong, D. G., Ryu, S. E., Sok, D. E. and Ahn, J. S. (2005) PTP1B inhibitory effect of abietane diterpenes isolated from Salvia miltiorrhiza. Biol. Pharm. Bull. 28, 1795-1797. https://doi.org/10.1248/bpb.28.1795
  11. Hanchar, H. J., Wallner, M. and Olsen, R. W. (2004) Alcohol effects on gamma-aminobutyric acid type A receptors: are extrasynaptic receptors the answer? Life Sci. 76, 1-8. https://doi.org/10.1016/j.lfs.2004.05.035
  12. He, Q., Titley, H., Grasselli, G., Piochon, C. and Hansel, C. (2013) Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD. J. Neurophysiol. 109, 1333-1342. https://doi.org/10.1152/jn.00350.2012
  13. Hicklin, T. R., Wu, P. H., Radcliffe, R. A., Freund, R. K., Goebel-Goody, S. M., Correa, P. R., Proctor, W. R., Lombroso, P. J. and Browning, M. D. (2011) Alcohol inhibition of the NMDA receptor function, long-term potentiation, and fear learning requires striatal-enriched protein tyrosine phosphatase. Proc. Natl. Acad. Sci. U.S.A. 108, 6650-6655. https://doi.org/10.1073/pnas.1017856108
  14. Izumi, Y., Nagashima, K., Murayama, K. and Zorumski, C. F. (2005) Acute effects of ethanol on hippocampal long-term potentiation and long-term depression are mediated by different mechanisms. Neuroscience 136, 509-517. https://doi.org/10.1016/j.neuroscience.2005.08.002
  15. Jaffe, D. and Johnston, D. (1990) Induction of long-term potentiation at hippocampal mossy-fiber synapses follows a Hebbian rule. J. Neurophysiol. 64, 948-960. https://doi.org/10.1152/jn.1990.64.3.948
  16. Johnston, D., Williams, S., Jaffe, D. and Gray, R. (1992) NMDA-receptor-independent long-term potentiation. Annu. Rev. Physiol. 54, 489-505. https://doi.org/10.1146/annurev.ph.54.030192.002421
  17. Kim, D. H., Jeon, S. J., Jung, J. W., Lee, S., Yoon, B. H., Shin, B. Y., Son, K. H., Cheong, J. H., Kim, Y. S., Kang, S. S., Ko, K. H. and Ryu, J. H. (2007) Tanshinone congeners improve memory impairments induced by scopolamine on passive avoidance tasks in mice. Eur. J. Pharmacol. 574, 140-147. https://doi.org/10.1016/j.ejphar.2007.07.042
  18. Komatsu, Y., Nakajima, S. and Toyama, K. (1991) Induction of longterm potentiation without participation of N-methyl-D-aspartate receptors in kitten visual cortex. J. Neurophysiol. 65, 20-32. https://doi.org/10.1152/jn.1991.65.1.20
  19. Koob, G. F. (2004) A role for GABA mechanisms in the motivational effects of alcohol. Biochem. Pharmacol. 68, 1515-1525. https://doi.org/10.1016/j.bcp.2004.07.031
  20. Li, M., Lu, Y., Hu, Y., Zhai, X., Xu, W., Jing, H., Tian, X., Lin, Y., Gao, D. and Yao, J. (2014) Salvianolic acid B protects against acute ethanol-induced liver injury through SIRT1-mediated deacetylation of p53 in rats. Toxicol. Lett. 228, 67-74. https://doi.org/10.1016/j.toxlet.2014.04.011
  21. Liguori, A. and Robinson, J. H. (2001) Caffeine antagonism of alcoholinduced driving impairment. Drug Alcohol Depend. 63, 123-129. https://doi.org/10.1016/S0376-8716(00)00196-4
  22. Lovinger, D. M., White, G. and Weight, F. F. (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243, 1721-1724. https://doi.org/10.1126/science.2467382
  23. Lu, K. H., Liu, C. T., Raghu, R. and Sheen, L. Y. (2012) Therapeutic potential of chinese herbal medicines in alcoholic liver disease. J. Tradit. Complement. Med. 2, 115-122. https://doi.org/10.1016/S2225-4110(16)30084-0
  24. Ron, D. (2004) Signaling cascades regulating NMDA receptor sensitivity to ethanol. Neuroscientist 10, 325-336. https://doi.org/10.1177/1073858404263516
  25. Semyanov, A., Walker, M. C. and Kullmann, D. M. (2003) GABA uptake regulates cortical excitability via cell type-specific tonic inhibition. Nat. Neurosci. 6, 484-490. https://doi.org/10.1038/nn1043
  26. Spinetta, M. J., Woodlee, M. T., Feinberg, L. M., Stroud, C., Schallert, K., Cormack, L. K. and Schallert, T. (2008) Alcohol-induced retrograde memory impairment in rats: prevention by caffeine. Psychopharmacology (Berl.) 201, 361-371. https://doi.org/10.1007/s00213-008-1294-5
  27. Steffensen, S. C., Nie, Z., Criado, J. R. and Siggins, G. R. (2000) Ethanol inhibition of N-methyl-D-aspartate responses involves presynaptic gamma-aminobutyric acid(B) receptors. J. Pharmacol. Exp. Ther. 294, 637-647.
  28. Wallner, M., Hanchar, H. J. and Olsen, R. W. (2003) Ethanol enhances ${\alpha}_4{\beta}_3{\delta}$ and ${\alpha}_6{\beta}_3{\delta}\;{\gamma}$-aminobutyric acid type A receptors at low concentrations known to affect humans. Proc. Natl. Acad. Sci. U.S.A. 100, 15218-15223. https://doi.org/10.1073/pnas.2435171100
  29. Wei, W., Faria, L. C. and Mody, I. (2004) Low ethanol concentrations selectively augment the tonic inhibition mediated by delta subunitcontaining GABAA receptors in hippocampal neurons. J. Neurosci. 24, 8379-8382. https://doi.org/10.1523/JNEUROSCI.2040-04.2004
  30. Yaka, R., Phamluong, K. and Ron, D. (2003) Scaffolding of Fyn kinase to the NMDA receptor determines brain region sensitivity to ethanol. J. Neurosci. 23, 3623-3632. https://doi.org/10.1523/JNEUROSCI.23-09-03623.2003
  31. Yi, J. H., Park, H. J., Kim, B. C., Kim, D. H. and Ryu, J. H. (2016) Evidences of the role of the rodent hippocampus in the non-spatial recognition memory. Behav. Brain Res. 297, 141-149. https://doi.org/10.1016/j.bbr.2015.10.018

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