출생 전 스트레스와 감금 스트레스가 흰쥐 편도복합체 별아교세포에 미치는 영향: I. 별아교세포의 세포체에 미치는 영향

Effects of Prenatal and Restraint Stress on Astrocytes of Amygdala Complex of Rat: I. Effects on the Astrocytic Cell Body

  • 이지용 (연세대학교 원주의과대학 해부학교실) ;
  • 최병영 (연세대학교 원주의과대학 해부학교실) ;
  • 김동희 (연세대학교 원주의과대학 환경의생물학교실) ;
  • 정원석 (연세대학교 원주의과대학 해부학교실) ;
  • 조병필 (연세대학교 원주의과대학 해부학교실) ;
  • 양영철 (연세대학교 원주의과대학 해부학교실)
  • Lee, Ji-Yong (Department of Anatomy, Yonsei University, Wonju College of Medicine) ;
  • Choi, Byoung-Young (Department of Anatomy, Yonsei University, Wonju College of Medicine) ;
  • Kim, Dong-Heui (Department of Environmental Medical Biology, Yonsei University, Wonju College of Medicine) ;
  • Jung, Won-Sug (Department of Anatomy, Yonsei University, Wonju College of Medicine) ;
  • Cho, Byung-Pil (Department of Anatomy, Yonsei University, Wonju College of Medicine) ;
  • Yang, Young-Chul (Department of Anatomy, Yonsei University, Wonju College of Medicine)
  • 발행 : 2008.09.30

초록

신경계통의 가소성은 신경세포의 변화에 의해 이루어질 뿐 아니라 신경아교세포의 변화에 의해서도 이루어진다. 신경아교세포 중 별아교세포는 신경세포의 기능을 조절하므로 정상적인 뇌의 기능을 유지하는데 매우 중요하다. 뇌에서 편도복합체는 위험 혹은 유해한 일련의 감각정보를 받아들이는 구역으로 받아들인 일련의 이와 같은 정보를 통합하고 변환시켜 공포라는 감정을 만들어낸다. 이런 과정은 편도복합체 신경세포에서 분비되는 신경전달물질의 균형변화에 의해 이루어지며, 신경전달물질의 조절에 별아교세포가 관여하므로 본 연구에서는 출생 전 스트레스와 성장 후에 받은 스트레스가 편도복합체 별아교세포의 세포체에 어떤 영향을 미치는지 조사하였다. 이를 위해 흰쥐를 스트레스를 받지 않은 대조군 (CON), 성장 후 스트레스를 받은 군 (CONR), 출생 전 스트레스를 받은 군 (PNS), 출생 전 스트레스와 성장 후 스트레스를 모두 받은 군 (PNSR)으로 구분하였다. 별아교세포는 GFAP 항체를 이용한 면역조직화학 염색을 시행하여 확인하였으며, methylene blue/azure II로 대조 염색하였다. Neurolucida 프로그램을 이용하여 계측한 별아교세포의 세포체는 일부 편도복합체 신경핵에서 출생 전 스트레스를 받은 PNS군이 대조군에 비하여 면적이 증가하였으며, 이런 경향은 출생 전 스트레스를 받고 다시 성장 후 스트레스를 받은 PNSR군에서 더욱 증가하였다. 따라서 흰쥐의 편도복합체에 분포하는 별아교세포는 스트레스에 영향을 받아 비대해지는 경향을 보인 것으로 나타났으며, 출생 전 스트레스가 성장 후에도 영향을 미치는 것으로 사료된다.

The plasticity of nervous system is generated not only due to changes in neurons but also due to changes in neuroglial cells. Astrocyte is important for maintaining the normal brain function and controlling the neuronal functions. The amygdala receives an array of important sensory information of danger signals. This information is further transduced and integrated to produce the highly adaptive emotion, fear. In this study, morphometric changes in the cell bodies of astrocytes in the amygdala, induced by prenatal stress and restraint stress were examined. For this purpose. rats were classified into 4 groups; control group (CON), only restraint-stressed (starting on P90 for 3 days) group (CONR), prenatally-stressed group (PNS), and prenatally and restraint (on P90 for 3 days) stressed group (PNSR). Astrocytes were verified with anti-GFAP immunohistochemistry, counter stained with methylene blue/azure II and were examined using the Neurolucida. Results showed that astrocytes in the amygdala of PNS rats had significantly larger cell bodies than did CON rats and this was enhanced further by restraint stress. Thus this data showed that hypertrophy of the astrocytic cell bodies of amygdala complex is induced by prenatal and restraint stress.

키워드

참고문헌

  1. Adolphs R, Tranel D, Damasio H, Damasio AR: Fear and the human amygdala. J Neurosci 15 : 5879-5891, 1995 https://doi.org/10.1523/JNEUROSCI.15-09-05879.1995
  2. Barbazanges A, Piazza PV, Moal ME, Maccari S: Maternal glucocorticoids secretion mediates long-term effects of prenatal stress. J Neurosci 16(12) : 3943-3949, 1996 https://doi.org/10.1523/JNEUROSCI.16-12-03943.1996
  3. Carrasco GA, van de Kar LD: Neuroendocrine pharmacology of stress. Eur J Pharmacol 463 : 235-272, 2003 https://doi.org/10.1016/S0014-2999(03)01285-8
  4. Chang SJ, Koh SB, Kang MG, Cha BS, Park JK, Hyun SJ, Park JH, Kim SA, Kang DM, Chang SS, Lee KJ, Ha EH, Ha M, Woo JM, Cho JJ, Kim HS, Park JS: Epidemiology of psychosocial distress in Korean employees. J Prev Med Public Health 38(1) : 25-37, 2005. (Korean)
  5. Costello EJ, Angold A: Anxiety disorders in children and adolescents; In Epidemiology. New York, London, Guilford, pp. 109-124, 1995
  6. Dayas CV, Buller KM, Crane JW, Xu Y, Day TA: Stressor categorization: acute physical and psychological stressors elicit distinctive reccruitment patterns in the amygdala and in medullary noradrenergic cell groups. Eur J Neurosci 14(7) : 1143-1152. 2001 https://doi.org/10.1046/j.0953-816x.2001.01733.x
  7. Dayas CV, Buller KM, Day TA: Neuroendocrine responses to an emotional stress: evidence for involvement of the medial but not the central amygdala. Eur J Neurosci 11(7) : 2312-2322, 1999 https://doi.org/10.1046/j.1460-9568.1999.00645.x
  8. De Bellis MD, Casey BJ, Dahl RE, Birmaher B, Williamson DE, Thomas KM, Axelson DA, Fristaci K, Boring AM, Hall J, Ryan ND: A pilot study of amygdala volumes in pediatric generalized anxiety disorders. Biol Psychiatry 48 : 51-57, 2000 https://doi.org/10.1016/S0006-3223(00)00835-0
  9. Fadda P, Fatta W: Stress-induced sleep deprivation modifies corticotropin releasing factor levels and CRF binding in rat brain and pituitary. Pharmacol Res 35(5) : 443-446, 1997 https://doi.org/10.1006/phrs.1997.0155
  10. Habib KE, Gold PW, Chrousos GP: Neuroendocrinology of stress. Endocrinol Metab Clin North Am 30(3) : 695-728, 2001 https://doi.org/10.1016/S0889-8529(05)70208-5
  11. Hansen A, Jorgenesen OS, Bolwig TG, Barry DI: Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain. Brain Res 531(1-2) : 307-11, 1990 https://doi.org/10.1016/0006-8993(90)90791-9
  12. Khurgel M, Ivy GO: Astrocytes in kindling: relevance to epileptogenesis. Epilepsy Res 26(1) : 163-175, 1996 https://doi.org/10.1016/S0920-1211(96)00051-4
  13. Kraig RP, Dong LM, Thisted R, Jaeger CB: Spreading depression increases immunohistochemical staining of glial fibrillary acidic protein. J Neurosci 11(7) : 2187-2198, 1991 https://doi.org/10.1523/JNEUROSCI.11-07-02187.1991
  14. Muller CM: Glial cells and activity dependent central nervous system plasticity. In: Knobil E and Ransom BR, eds, Neuroglia, New York, Oxford University Press, pp. 221-302, 1995
  15. National Institute of Mental Health. Facts about anxiety disorders. http://www.nimh.nih.gov/publicat/adfacts.cfm, 2004
  16. Ouyang YB, Giffard RG: Changes in the astrocytic mitochondrial function with stress: effects of Bcl-2 family proteins. Neurochem Int 45(2-3) : 371-379, 2004 https://doi.org/10.1016/j.neuint.2003.07.006
  17. Paxinos G, Watson C: The rat brain. In stereotaxic coordinates. Acdemic Press, San Diego, pp. 22-44. 1998
  18. Phan KL, Wager T, Tayler SF, Liberzon I: Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and MRI. Neuroimage 16 : 331-348, 2002 https://doi.org/10.1006/nimg.2002.1087
  19. Salm AK, Pavelko M, Krouse M, Webster W, Kraszpulski M, Birkle DL: Lateral amygdaloid nucleus expansion in adult rats is associated with exposure to prenatal stress. Develop Brain Res 148 : 159-167, 2004 https://doi.org/10.1016/j.devbrainres.2003.11.005
  20. Sarnyai Z, Biro E, Gardi J, Vecsernyes M, Julesz J, Telgedy G: Brain corticotropin-releasing factor mediates 'nxiety-like' behavior induced by cocaine withdrawal in rats. Brain Res 675 (1-2) : 89-97, 1995 https://doi.org/10.1016/0006-8993(95)00043-P
  21. Sirevaag AM, Greenough WT: Differential rearing effects on rat visual cortex synapses. III. Neuronal and glial nuclei, boutons, dendrites, and capillaries. Brain Res 424(2) : 320-332, 1987 https://doi.org/10.1016/0006-8993(87)91477-6
  22. Sirevaag AM, Greenough WT: Plasticity of GFAP-immunoreactive astrocyte size and number in visual cortex of rats reared in complex environments. Brain Res 540(1-2) : 273-278, 1991 https://doi.org/10.1016/0006-8993(91)90517-Y
  23. Sirevaag AM, Smith S, Greenough WT: Rats reared in a complex environment have larger astrocytes with more processes than rats raised socially or individually. Society for Neuroscience Abstracts 14 : 1135, 1988
  24. Song DY, Park JC, Park BG, Lee JS, Choi BY, Yang YC, Kang HS, Cho BP: Neuroglial proliferative activity following medial forebrain bundle axotomy. Korean J Anat 37(4) : 329-336, 2004. (Korean)
  25. Stott DN: Follow-up study from birth of the effects of prenatal stress. Dev Med Child Neurol 15 : 770-787, 1996 https://doi.org/10.1111/j.1469-8749.1973.tb04912.x
  26. U.S. Department of Health and Human Services. Mental Health: A report of the surgeon general. Chapter 4. Sec. 2. Anxiety disorders. http://www.surgeongeneral.gov/library/chapter4/sec2.html, 1999
  27. Valle M, Mayo W, Dellu F, Le Moal M, Simon H, Maccari S: Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: Correlation with stress-induced corticosterone secretion. J Neurosci 17(7) : 2626-2636, 1997 https://doi.org/10.1523/JNEUROSCI.17-07-02626.1997
  28. Wenzei J, Lammert G, Meyer U, Krug M: The influence of longterm potentiation on the spatial relationship between astrocyte processes and potentiated synapses in the dentate gyrus neuropil of rat brain. Brain Res 560(1-2) : 122-131, 1991 https://doi.org/10.1016/0006-8993(91)91222-M
  29. Yang YC, Cho BP, Kang HS: Immunohistochemical and immunocytochemical study about the glial fibrillary acidic protein in the tanycytes of the area postrema of bat. Korean J Electron Microscopy 30(4) : 377-387, 2000. (Korean)