DOI QR코드

DOI QR Code

Effect of Acupuncture on Depression and Cell Proliferation in Hippocampal Gyrus Dentatus of Maternal-separated Rat Pups

침술 치료가 모성분리 새끼 쥐의 우울증과 해마의 치상회 세포증식에 미치는 영향

  • 박정식 (가천대학교 한의과대학) ;
  • 임형호 (가천대학교 한의과대학)
  • Received : 2019.03.29
  • Accepted : 2019.04.05
  • Published : 2019.04.30

Abstract

Objectives The loss of maternal care during early postnatal period may increase development of mood-related disorders, such as depression, anxiety, and personality disorders. In this study, the effect of acupuncture on depression in relation with cell proliferation in the hippocampal gyrus dentatus was investigated using maternal-separated rat pups. Methods On the postnatal 14th day, rat pups from six dams were grouped into following groups: maternal care group, maternal separation group, maternal separation and non-acupoint-acupunctured group, maternal separation and Zusanli-acupunctured group, and maternal separation and fluoxetine-treated group. Acupuncture was performed from postnatal 28th day to postnatal 37th day. The rat pups that belong in the maternal separation and fluoxetine-treated group were injected subcutaneously with 5 mg/kg fluoxetine hydrochloride once a day for the same period of time. To evaluate activity of the rat pups, open field test was performed. Immunohistochemistry for serotonin (5-hydroxytryptamine, 5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe and for 5-bromo-2'-deoxyuridine (BrdU) in the hippocampal gyrus dentatus was conducted. Results The present results reveal that the activity was decreased by maternal separation. In contrast, acupuncture at Zusanli overcame maternal separation-induced hypoactivity. Maternal separation suppressed TPH expression and 5-HT synthesis in the dorsal raphe and decreased cell proliferation in the hippocampal gyrus dentatus of rat pups. In contrast, acupuncture at Zusanli alleviated maternal separation-induced decrease of 5-HT synthesisand TPH expression. Conclusions The present results demonstrate that acupuncture at Zusanli ameliorated depressive state through increasing cell proliferation and enhancing 5-HT synthesis.

Keywords

References

  1. Aisa B, Elizalde N, Tordera R, Lasheras B, Del Rio J, Ramirez MJ. Effects of neonatal stress on markers of synaptic plasticity in the hippocampus: implications for spatial memory. Hippocampus. 2009;19(12):1222-31. https://doi.org/10.1002/hipo.20586
  2. Marais L, van Rensburg SJ, van Zyl JM, Stein DJ, Daniels WM. Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus. Neurosci Res. 2008;61(1):106-12. https://doi.org/10.1016/j.neures.2008.01.011
  3. Sung YH, Shin MS, Cho S, Baik HH, Jin BK, Chang HK, Lee EK, Kim CJ. Depression-like state in maternal rats induced by repeated separation of pups is accompanied by a decrease of cell proliferation and an increase of apoptosis in the hippocampus. Neurosci Lett. 2010;470(1):86-90. https://doi.org/10.1016/j.neulet.2009.12.063
  4. Park HJ, Lim S, Lee HS, Lee HJ, Yoo YM, Lee HJ, Kim SA, Yin CS, Seo JC, Chung JH. Acupuncture enhances cell proliferation in dentate gyrus of maternally-separated rats. Neurosci Lett. 2002;319(3):153-6. https://doi.org/10.1016/S0304-3940(01)02581-2
  5. Christiansen L, Tan Q, Iachina M, Bathum L, Kruse TA, McGue M, Christensen K. Candidate gene polymorphisms in the serotonergic pathway: influence on depression symptomatology in an elderly population. Biol Psychiatry. 2007;61(2):223-30. https://doi.org/10.1016/j.biopsych.2006.03.046
  6. Neumeister A. Tryptophan depletion, serotonin, and depression: where do we stand? Psychopharmacol Bull. 2003;37(4):99-115.
  7. Fairhall SL, Sharma S, Magnusson J, Murphy B. Memory related dysregulation of hippocampal function in major depressive disorder. Biol Psychol. 2010;85(3):499-503. https://doi.org/10.1016/j.biopsycho.2010.09.002
  8. Warner-Schmidt JL, Duman RS. Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus. 2006;16(3):239-49. https://doi.org/10.1002/hipo.20156
  9. Campbell S, Marriott M, Nahmias C, MacQueen GM. Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry. 2004;161(4): 598-607. https://doi.org/10.1176/appi.ajp.161.4.598
  10. Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59(12): 1116-27. https://doi.org/10.1016/j.biopsych.2006.02.013
  11. Baek SS, Jun TW, Kim KJ, Shin MS, Kang SY, Kim CJ. Effects of postnatal treadmill exercise on apoptotic neuronal cell death and cell proliferation of maternal-separated rat pups. Brain Dev. 2012;34(1):45-56. https://doi.org/10.1016/j.braindev.2011.01.011
  12. Dos Santos JG Jr, Kawano F, Nishida MM, Yamamura Y, Mello LE, Tabosa A. Antidepressive-like effects of electroacupuncture in rats. Physiol Behav. 2008;93(1-2): 155-9. https://doi.org/10.1016/j.physbeh.2007.08.014
  13. Hwang IK, Chung JY, Yoo DY, Yi SS, Youn HY, Seong JK, Yoon YS. Comparing the effects of acupuncture and electroacupuncture at Zusanli and Baihui on cell proliferation and neuroblast differentiation in the rat hippocampus. J Vet Med Sci. 2010;72(3):279-84. https://doi.org/10.1292/jvms.09-0374
  14. Kim EH, Kim YJ, Lee HJ, Huh Y, Chung JH, Seo JC, Kang JE, Lee HJ, Yim SV, Kim CJ. Acupuncture increases cell proliferation in dentate gyrus after transient global ischemia in gerbils. Neurosci Lett. 2001;297(1):21-4. https://doi.org/10.1016/S0304-3940(00)01656-6
  15. Durand M, Berton O, Aguerre S, Edno L, Combourieu I, Mormède P, Chaouloff F. Effects of repeated fluoxetine on anxiety-related behaviours, central serotonergic systems, and the corticotropic axis axis in SHR and WKY rats. Neuropharmacology. 1999;38(6):893-907. https://doi.org/10.1016/S0028-3908(99)00009-X
  16. Zhang LX, Levine S, Dent G, Zhan Y, Xing G, Okimoto D, Kathleen Gordon M, Post RM, Smith MA. Maternal deprivation increases cell death in the infant rat brain. Brain Res Dev Brain Res. 2002;133(1):1-11. https://doi.org/10.1016/S0926-6410(01)00118-5
  17. Lim S, Ryu YH, Kim ST, Hong MS, Park HJ. Acupuncture increases neuropeptide Y expression in hippocampus of maternally-separated rats. Neurosci Lett. 2003;343(1):49-52. https://doi.org/10.1016/S0304-3940(03)00317-3
  18. Braun K, Lange E, Metzger M, Poeggel G. Maternal separation followed by early social deprivation affects the development of monoaminergic fiber systems in the medial prefrontal cortex of Octodon degus. Neuroscience. 2000;95(1):309-18. https://doi.org/10.1016/S0306-4522(99)00420-0
  19. Lee SH, Chung SH, Lee JS, Kim SS, Shin HD, Lim BV, Jang MH, Kim H, Kim EH, Kim CJ. Effects of acupuncture on the 5-hydroxytryptamine synthesis and tryptophan hydroxylase expression in the dorsal raphe of exercised rats. Neurosci Lett. 2002;332(1):17-20. https://doi.org/10.1016/S0304-3940(02)00900-X
  20. Arborelius L, Hawks BW, Owens MJ, Plotsky PM, Nemeroff CB. Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation. Psychopharmacology (Berl). 2004;176(3-4):248-55. https://doi.org/10.1007/s00213-004-1883-x
  21. Yang LM, Hu B, Xia YH, Zhang BL, Zhao H. Lateral habenula lesions improve the behavioral response in depressed rats via increasing the serotonin level in dorsal raphe nucleus. Behav Brain Res. 2008;188(1):84-90. https://doi.org/10.1016/j.bbr.2007.10.022
  22. Takagi J, Yonehara N. Serotonin receptor subtypes involved in modulation of electrical acupuncture. Jpn J Pharmacol. 1998;78(4):511-4. https://doi.org/10.1254/jjp.78.511
  23. Chen A. An introduction to sequential electric acupuncture (SEA) in the treatment of stress related physical and mental disorders. Acupunct Electrother Res. 1992;17(4):273-83. https://doi.org/10.3727/036012992816357675
  24. Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4(11):1313-7. https://doi.org/10.1038/3305
  25. Fabricius K, Wörtwein G, Pakkenberg B. The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus. Brain Struct Funct. 2008;212(5):403-6. https://doi.org/10.1007/s00429-007-0169-6
  26. Lee HJ, Kim JW, Yim SV, Kim MJ, Kim SA, Kim YJ, Kim CJ, Chung JH. Fluoxetine enhances cell proliferation and prevents apoptosis in dentate gyrus of maternally separated rats. Mol Psychiatry. 2001;610(6):725-8.
  27. Hulshof HJ, Novati A, Sgoifo A, Luiten PG, den Boer JA, Meerlo P. Maternal separation decreases adult hippocampal cell proliferation and impairs cognitive performance but has little effect on stress sensitivity and anxiety in adult Wistar rats. Behav Brain Res. 2011; 216(2):552-60. https://doi.org/10.1016/j.bbr.2010.08.038
  28. Banasr M, Hery M, Brezun JM, Daszuta A. Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrus. Eur J Neurosci. 2001;14(9):1417-24. https://doi.org/10.1046/j.0953-816x.2001.01763.x
  29. Brezun JM, Daszuta A. Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience. 1999;89(4):999-1002. https://doi.org/10.1016/S0306-4522(98)00693-9