题名

Inhibitory effect of yokukansan on the decrease in the hippocampal excitatory amino acid transporter EAAT2 in stress-maladaptive mice

DOI

10.1016/j.jtcme.2016.12.005

作者

Hiroko Miyagishi;Minoru Tsuji;Atsumi Saito;Kazuya Miyagawa;Hiroshi Takeda

关键词

Yokukansan ; Restraint stress ; Excitatory amino acid transporter ; Hippocampus ; Glutamate

期刊名称

Journal of Traditional and Complementary Medicine

卷期/出版年月

7卷4期(2017 / 10 / 01)

页次

371 - 374

内容语文

英文

中文摘要

Chronic stress is widely recognized as a risk factor for the development of major depression and anxiety disorders. Recently, we reported that yokukansan (YKS), a traditional Japanese herbal medicine, alleviated emotional abnormality in stress-maladaptive mice. The aim of the present study was to examine the effect of YKS on the expression of excitatory amino acid transporter (EAAT) 1-4 in the prefrontal cortex and hippocampus in stress-maladaptive mice. Mice were chronically exposed to inadaptable stress, i.e. repeated restraint stress for 240 min/day for 14 days. After the final exposure to stress, brains of mice were rapidly removed and the hippocampus and prefrontal cortex were dissected. Expressions of EAAT1- 4 and glial fibrillary acidic protein (GFAP), a marker of astrocytes, in the brain tissues were analyzed by western blotting. Western blot analysis revealed that the expression level of EAAT2 was specifically decreased in the hippocampus of stress-maladaptive mice while there were no changes in the level of GFAP, and this change was inhibited by chronic treatment with YKS. In contrast, no changes were observed in the levels of EAAT1, EAAT3 or EAAT4 in stress-maladaptive mice. These results suggest that YKS may protect against the decrease in hippocampal EAAT2 expression induced by stress maladaptation, and this may contribute, at least in part, to the improvement of emotional abnormality.

主题分类 醫藥衛生 > 中醫藥學
参考文献
  1. Beart, PM,O'Shea, RD(2007).Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement.Br J Pharmacol,150,5-17.
  2. Breslau, N,Davis, GC(1986).Chronic stress and major depression.Arch Gen Psychiatry,43,309-314.
  3. Chen, JX,Yao, LH,Xu, BB(2014).Glutamate transporter 1-mediated antidepressant-like effect in a rat model of chronic unpredictable stress.J Huazhong Univ Sci Technolog Med Sci.,34,838-844.
  4. Choudary, PV,Molnar, M,Evans, SJ(2005).Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression.Proc Natl Acad Sci U. S. A.,102,15653-15658.
  5. Ferrero, AJ,Cereseto, M,Reinés, A(2005).Chronic treatment with fluoxetine decreases seizure threshold in naïve but not in rats exposed to the learned helplessness paradigm: correlation with the hippocampal glutamate release.Prog Neuropsychopharmacol Biol Psychiatry,29,678-686.
  6. Furuta, A,Rothstein, JD,Martin, LJ(1997).Glutamate transporter protein subtypes are expressed differentially during rat CNS development.J Neurosci,17,8363-8375.
  7. Grahn, RE,Watkins, LR,Maier, SF(2000).Impaired escape performance and enhanced conditioned fear in rats following exposure to an uncontrollable stressor are mediated by glutamate and nitric oxide in the dorsal raphe nucleus.Behav Brain Res,112,33-41.
  8. Hunter, AM,Balleine, BW,Minor, TR(2003).Helplessness and escape performance: glutamate-adenosine interactions in the frontal cortex.Behav Neurosci.,117,123-135.
  9. Ikarashi, Y,Iizuka, S,Imamura, S(2009).Effects of yokukansan, a traditional Japanese medicine, on memory disturbance and behavioral and psychological symptoms of dementia in thiamine-deficient rats.Biol Pharm Bull,32,1701-1709.
  10. Imbe, H,Kimura, A,Donishi, T,Kaneoke, Y(2012).Chronic restraint stress decreases glial fibrillary acidic protein and glutamate transporter in the periaqueductal gray matter.Neuroscience,223,209-218.
  11. Kalandadze, A,Wu, Y,Robinson, MB(2002).Protein kinase C activation decreases cell surface expression of the GLT-1 subtype of glutamate transporter. Requirement of a carboxyl-terminal domain and partial dependence on serine 486.J Biol Chem,277,45741-45750.
  12. Kawakami, Z,Ikarashi, Y,Kase, Y(2010).Glycyrrhizin and its metabolite 18 beta-glycyrrhetinic acid in glycyrrhiza, a constituent herb of yokukansan, amelio-rate thiamine deficiency-induced dysfunction of glutamate transport in cultured rat cortical astrocytes.Eur J Pharmacol.,626,154-158.
  13. Kawakami, Z,Kanno, H,Ueki, T(2009).Neuroprotective effects of yokukansan, a traditional Japanese medicine, on glutamate-mediated excitotoxicity in cultured cells.Neuroscience,159,1397-1407.
  14. Liu, WX,Wang, J,Xie, ZM(2016).Regulation of glutamate transporter 1 via BDNF-TrkB signaling plays a role in the anti-apoptotic and antidepressant effects of ketamine in chronic unpredictable stress model of depression.Psychopharmacology,233,405-415.
  15. Mizukami, K,Asada, T,Kinoshita, T(2009).A randomized cross-over study of a traditional Japanese medicine (kampo), yokukansan, in the treatment of the behavioural and psychological symptoms of dementia.Int J Neuro-psychopharmacol,12,191-199.
  16. Nakagawasai, O,Yamadera, F,Iwasaki, K(2007).Preventive effect of kami-untan-to on performance in the forced swimming test in thiamine-deficient mice: relationship to functions of catecholaminergic neurons.Behav Brain Res,177,315-321.
  17. Petty, F,McChesney, C,Kramer, G(1985).Intracortical glutamate injection produces helpless-like behavior in the rat.Pharmacol Biochem Behav,22,531-533.
  18. Sheldon, AL,González, MI,Krizman-Genda, EN,Susarla, BT,Robinson, MB(2008).Ubiquitination-mediated internalization and degradation of the astroglial glutamate transporter, GLT-1.Neurochem Int,53,296-308.
  19. Tanaka, K,Watase, K,Manabe, T(1997).Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1.Science,276,1699-1702.
  20. Tsuji, M,Takeuchi, T,Miyagawa, K(2014).Yokukansan, a traditional Japanese herbal medicine, alleviates the emotional abnormality induced by maladaptation to stress in mice.Phytomedicine,21,363-371.
  21. Willner, P(2005).Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS.Neuropsychobiology,52,90-110.
  22. Zhu, MY,Wang, WP,Huang, J,Feng, YZ,Regunathan, S,Bissette, G(2008).Repeated immobilization stress alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels.Neurochem Int,53,346-354.
  23. Zink, M,Vollmayr, B,Gebicke-Haerter, PJ,Henn, FA(2010).Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression.Neuropharmacology,58,465-473.