동의신경정신과학회지 (Journal of Oriental Neuropsychiatry)

  • 제20권1호
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  • Pages.75-87
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  • 2009
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  • 1226-6396(pISSN)
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  • 2234-4942(eISSN)
대한한방신경정신과학회 (The Korean Society of Oriental Neuropsychiatry)
권호 표지

트리메틸틴에 의해 유도된 흰쥐의 학습과 기억력 손상에 대한 육미지황탕가미방의 신경보호 효과

Neuroprotective Effect of Yukmijihwamg-tang(Liuweidihuangtang) Gamibang on the Deficits of Learning and Memory in Trimethyltin-Intoxicated Rats

  • 정희상 (동국대학교 한의과대학 신경정신과학교실) ;
  • 김근우 (동국대학교 한의과대학 신경정신과학교실) ;
  • 구병수 (동국대학교 한의과대학 신경정신과학교실)
  • Jeung, Hee-Sang (Dept. of Neuropsychiatry, College of Korean Medicine, Dongguk University) ;
  • Kim, Geun-Woo (Dept. of Neuropsychiatry, College of Korean Medicine, Dongguk University) ;
  • Koo, Byung-Soo (Dept. of Neuropsychiatry, College of Korean Medicine, Dongguk University)
  • 발행 : 2009.03.30
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초록

목적 : 이 연구는 알쯔하이머 병에 대한 육미지황가미방의 효과를 조사하였다. 육미지황가미방은 산약, 산수유, 복령, 목단피, 구기자, 택사, 숙지황을 포함한 여러 가지 한약재의 전탕액으로 치매의 한약 치료제로 널리 사용되어 왔다. 방법 : 이 약물의 신경보호 작용을 조사하기 위해, 수중미로를 사용하여 학습과 기억에 대한 육미지황가미방의 효과를 평가 했고, 트리메틸틴은 강력한 유독물질로 선택적으로 중추신경계와 면역계의 세포를 파괴시킨다. 트리메틸틴(6.0 mg/kg, i.p.)주입 후, 쥐에게 육미지황가미방(400mg/kg, p.o.)를 2주 동안 날마다 복용시켰으며, 수중미로를 수행시켰다. 결과 : 육미지황가미방을 트리메틸틴에 노출시킨 쥐에 투약했으며, 그들은 수중미로에서 학습과 기억의 향상을 보였고, 이는 육미지황가미방이 어떠한 환경에서는 트리메틸틴으로 유발된 신경퇴화 후 중추신경계의 결손을 감소시킬 수 있음을 보여준다. 결론 : 이러한 결론은 육미지황가미방이 인지능력을 증가시키고, 트리메틸틴으로 유발된 신경퇴화에서 콜린 아세틸전환효소의 정도를 변화시킬 수 있음을 보여준다.

키워드

참고문헌

  1. Giacobini E. Cholinergic foundations of Alzheimer's disease therapy. J. Physiol. Paris. 1998;92:283-7. https://doi.org/10.1016/S0928-4257(98)80034-X
  2. Op den Velde W, Stam F. C. Some cerebral proteins and enzyme systems in Alzheimer's presenile and senile dementia. J. Am. Geriatr. Soc. 1976;24:12-6.
  3. Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE. Neurotransmitter enzyme abnormalities in senile dementia. ChAT and glutamic acid decarboxylase activities in necropsy brain tissue. J. Neurol. Sci. 1977;34:247-65. https://doi.org/10.1016/0022-510X(77)90073-9
  4. Giacobini E. Cholinergic function and Alzheimer's disease. Int. J. Geriatr. Psychiatry. 2003;18:1-5. https://doi.org/10.1002/gps.649
  5. Balaban CD, O’Callaghan JP, Billingsley ML. Trimetyltin-induced neuronal damage in the rat brain: comparative studies using silver degeneration stains, immunocytochemistry and immunoassay for neurotypic and gliotypic proteins. Neuroscience. 1988;26:337-61. https://doi.org/10.1016/0306-4522(88)90150-9
  6. Brabeck C. Michetti F. Geloso MC, Corvino V, Goezalan F, Meyermann R, Schluesener H. Expression of EMAP-II cativated monocytes/microglial cells in different regions of the rat hippocampus after trimetyltin-induced brain damage. Exp. Neurol. 2002;177:341-6. https://doi.org/10.1006/exnr.2002.7985
  7. Geloso MC, Vinesi P, Michetti F. Parvalbumin-immunoreactive neurons are not affected by trimethyltin-induced neurodegeneration in the rat hippocampus. Exp. Neurol. 1996;139:269-77. https://doi.org/10.1006/exnr.1996.0100
  8. Geloso MC, Vinesi P, Michetti F. Calretinin - containing neurons intrimethyltin - induced neurodegeneration in the rat hippocampus. An immunocytochemical study. Exp. Neurol. 1997;146:67-73. https://doi.org/10.1006/exnr.1997.6491
  9. Geloso MC, Vercelli A, Corvini V, Repici ME, Boca M, Haglid K, Zelano G, Michetti F. Cyclooxygenase-2 and caspase-3 expression in trimetyltin-induced apoptosis in the hippocampus. Exp. Neurol. 2002;175:152-60. https://doi.org/10.1006/exnr.2002.7866
  10. Geloso MC, Corvino V, Cavallo V, Toesca A, Guadagni E, Passalacqua R, Michetti F. Expression of astrocytic nestin in the rat hippocampus during trimethltin-induced neurodegeneration. Neurosci. Lett. 2004;357:103-6. https://doi.org/10.1016/j.neulet.2003.11.076
  11. Ishida N, Akaike M, Tsutsumi S, Kanai A, Masui M, Sadamatsu Y, Kuroda Y, Watanabe Y, McEwen BS, Kato N. Trimethyltin syndrome as a hippocampal degeneration model: temporal changes and neurochemical features of seizure susceptibility and learning impairment. Neuroscience. 1997;81:1183-91. https://doi.org/10.1016/S0306-4522(97)00220-0
  12. Koczyk D. How does trimetyltin affect the brain: facts and hypotheses. Acta Neurobiol. Exp. 1996;56:587-96.
  13. Dyer RS, Walsh TJ, Wonderlin WF, Bercegeay M. The trimetyltin syndrome in rats. Neurobehav. Toxicol. Teratol. 1982;4:127-33.
  14. Brown AW, Aldridge, WN, Street BW, Verschoyle RD. The behavioral and neuropathologic sequelae of intoxication by trimetyltin compounds in the rat. Am. J. Pathol. 1979;97:59-82.
  15. Chang LW, Dyer. RS. A time-course study of trimethyltin induced neuropathology in rat. Neurobehav. Toxicol. Teratol. 1983;5:443-59.
  16. Chang LW, Dyer RS. Septotemporal gradients of trimethyltin-induced hippocampal lesions. Neurobehav. Toxicol. Teratol. 1985;7:43-9.
  17. Alessandri B. FitzGerald RE. Schaeppi U, Krinke GJ, Classen W. The use of an unbaited tunnel maze in neurotoxicology: I. Trimethyltin-induced brain lesions. Neurotoxicology. 1994;15:349-58.
  18. Cannon RL, Paul DJ, Baisden RH, Woodruff ML. Alterations in self-grooming in the rat as a consequence of hippocampal damage. Psychobiology. 1992;20:205-18.
  19. Cohen CA, Messing RB, Sparber SB. Selective learning impairment of delayed reinforcement autoshaped behavior caused by low doses of trimethyltin. Psychopharmacology. 1987;93:301-7.
  20. Earley B, Burke M, Leonard BE. Behavioral, biochemical and histological effects of trimethyltin induced brain damage in the rat. Neurochem. Int. 1992;21:351-66. https://doi.org/10.1016/0197-0186(92)90186-U
  21. Hagan JJ, Jansen JHM, Broekkamp CLE. Selective behavioral impairment after acute intoxication with trimethyltin in rats. Neurotoxicology. 1988;9:53-74.
  22. Messing RB, Devauges, V. and Sara, S.J., Limbic forebrain toxin trimethyltin reduces behavioral suppression by clonidine. Pharmacol. Biochem. Behav., 1992;42:313-6. https://doi.org/10.1016/0091-3057(92)90532-K
  23. Segal M. Behavioral and physiological effects of trimethyltin in the rat hippocampus. Neurotoxicology. 1988;9:481-90.
  24. Swartzwelder HS, Hepler J, Holahan W, King SE, Leverenz HA, Miller PA, Myers RD. Impaired maze performance in the rat caused by trimethyltin treatment: Problem-solving deficits and perseveration. Neurobehav. Toxicol. Teratol. 1982;4:469-76.
  25. Woodruff ML, Baisden RH, Nonneman AJ. Anatomical and behavioral sequelae of fetal brain transplants in rats with trimethyltin-induced neurodegeneration. Neurotoxicology. 1991;12:427-44.
  26. O’Connell A, Earley B, Leonard BE. Effects of the GABA agonist THIP (gaboxadol) on trimethyltin-induced behavioral neurotoxicity in the rat. Med. Sci. Res. 1994;22:201-2.
  27. O’Connell A, Earley B, Leonard BE. The neuroprotective effect of racrne on trimethyltin induced memory and nuscarinic receptor dysfunction in the rat. Neurochem. Int. 1994;25:555-66. https://doi.org/10.1016/0197-0186(94)90154-6
  28. O'Connell A, Earley B, Leonard BE. The $\sigma$ ligand JO 1784 prevents trimethyltin-induced behavioral and $\sigma$ -receptor dysfunction in the rat. Pharmacol. Toxicol. 1996;78:296-302. https://doi.org/10.1111/j.1600-0773.1996.tb01378.x
  29. Walsh TJ, Miller DB, Dyer RS. Trimethyltin, a selective limbic system neurotoxicant, impairs radial-arm maze performance. Neurobehav. Toxicol. Teratol. 1982; 4:177-83.
  30. Earley B, Burke M, Leonard BE, Gouret CJ, Junien JL. A comparison of the psychopharmacological profiles of phencyclidine, ketamine and (+) SKF 10,047 in the trimethyltin rat model. Neuropharmacology. 1990;29:695-703. https://doi.org/10.1016/0028-3908(90)90121-7
  31. Loullis CC, Dean RL, Lippa AS, Clody DE, Coupet J. Hippocampal muscarinic receptor loss following trimethyltin administration. Pharmacol. Bioche. Behav. 1985;22:147-51. https://doi.org/10.1016/0091-3057(85)90498-8
  32. Swartzwelder HS, Dyer RS, Holahan W, Myers RD. Activity changes in rats following acute trimethyltin exposure. Neurotoxicology. 1981;2:593-8.
  33. Woodruff ML, Baisden RH. Trimethyltin neurotoxicity in the rat as an analogous model of Alzheimer’s disease. In Toxin-induced Models of Neurological Disorders, ed. M.L. Woodruff and A.J. Nonneman. Plenum Press. New York. 1994. pp. 319-35.
  34. Birks J, Grimley EV, Van Dongen M. The efficacy of antidepressants in the treatment of depression in dementia. Cochrane. Database Syst. Rev. 2002:CD003120.
  35. Kennedy DO, Scholey AB. Electroencephalograph effects of single doses of Ginkgo biloba and Panax ginseng in healthy young volunteers. Pharmacol. Biochem. Behav. 2003;75:687-700. https://doi.org/10.1016/S0091-3057(03)00126-6
  36. Rho S, Kang M, Choi B, Sim D, Lee J, Lee E, Cho C, Oh JW, Park S, Ko S, Shin M, Hong M, Bae H. Effects of Yukmijihwang-tang(Liuweidihuangtang) derivatives (YMJd), a memory enhancing herbal extract, on the gene-expression profile in the rat hippocampus. Biol. Pharm. Bull. 2005;28:87-93. https://doi.org/10.1248/bpb.28.87
  37. Park E, Kang M, Oh JW, Jung M, Park C, Cho C, Kim C, Ji S, Lee Y, Choi H, Kim H, Ko S, Shin M, Park S, Kim HT, Hong M, Bae H., Yukmijihwang-tang(Liuweidihuangtang) derivatives enhance cognitive processing in normal young adults: a double-blinded, placebo-controlled trial., Am. J. Chin. Med. 2005;33:107-15. https://doi.org/10.1142/S0192415X05002709
  38. Squire LR, Davis HP. The pharmacology of memory: a neurobiological perspective. Annu Rev Pharmacol Toxicol. 1981;21:323-56. https://doi.org/10.1146/annurev.pa.21.040181.001543
  39. Lanier LP, Issacson RL. Activity changes related to location of lesions in the hippocampus. Behav. Biol. 1975;13:59-65. https://doi.org/10.1016/S0091-6773(75)90793-2
  40. Agrawal AK et al. Restorative potential of cholinergic rich transplants in cholchicine induced lesioned rats: a comparative study of single and multiple micro-transplantation approach. Int. J. Devl Neuroscience. 2003;21:191-8. https://doi.org/10.1016/S0736-5748(03)00039-X
  41. Muir JL. Acetylcholine, aging, and Alzheimer’s disease. Pharmacol Biochem Behav. 1997;56:687-96. https://doi.org/10.1016/S0091-3057(96)00431-5
  42. Dickinson-Anson H, Winkler J, Fisher LJ, Song HJ, Poo M, Gage FH. Acetylcholine-secreting cells improve age-induced memory deficits. Mol Ther. 2003;8:51-61. https://doi.org/10.1016/S1525-0016(03)00145-X
  43. Rho S, Chung HS, Kang M, Lee E, Cho C, Kim H, Park S, KimHY, Hong M, Shin M, Bae H. Inhibition of production of reactive oxygen species and gene expression profile by treatment of ethanol extract of Moutan Cortex Radicis in oxidative stressed PC12 cells., Biol. Pharm. Bull. 2005;28:661-6. https://doi.org/10.1248/bpb.28.661
  44. Cui Y, Yan ZH, Hou SL, Chang ZF. Intelligence enhancement of radix Rehmanniae praeparata and some comments on its research. Zhongguo Zhong Yao ZaZhi. 2002;27:404-6, 456.
  45. Cui Y, Yan Z, Hou S, Chang Z. Effect of radix Rehmanniae preparata on the expression of c-fosand NGF in hippocampi and learning and memory in rats with damaged thalamic arcuate nucleus. Zhong Yao Cai. 2004;27:589-92.
  46. Wei RB, Huo HR, Li XQ, Zhou AX, Shen H, Tian JL. Study on antiinflammatory effect of a compound TCM agent containing ant extractive in animal models. Zhongguo Zhong Yao Za Zhi 2002;27:215-8.
  47. Dai Y, But PP, Chan YP, Matsuda H, Kubo M. Antipruritic and antiinflammatory effects of aqueous extract from Si-Wu-Tang. Biol. Pharm. Bull. 2002;25:1175-8. https://doi.org/10.1248/bpb.25.1175
  48. Kim MJ, Kim HN, Kang KS, Baek NI, Kim DK, Kim YS, Jeon BH, Kim SH. Methanol extract of Dioscoreae Rhizoma inhibits pro-inflammatory cytokines and mediators in the synoviocytes of rheumatoid arthritis. Int. Immunopharmacol. 2004;4:1489-97. https://doi.org/10.1016/j.intimp.2004.07.001
  49. Dai Y, Hang B, Huang Z. Inhibition of fructus Corni on experimental inflammation. Zhongguo Zhong Yao Za Zhi. 1992;17:307-9.
  50. Park WH, Joo ST, Park KK, Chang YC, Kim CH. Effects of the Geiji-Bokryung-Hwan on carrageenan-induced inflammation in mice and cyclooxygenase-2 in hepatoma cells of HepG2 and Hep3B. Immunopharmacol. Immunotoxicol. 2004;26:103-12.
  51. Isabell Mansuy. Contraint cAMP Signaling. Neuron. 2004;41:4-6. https://doi.org/10.1016/S0896-6273(03)00845-6