Stress-induced Decrease of Granule Cell Proliferation in Adult Rat Hippocampus: Assessment of Granule Cell Proliferation Using High Doses of Bromodeoxyuridine Before and After Restraint Stress

  • Kim, Sung-Jin (Department of Pharmacology, Korea University College of Medicine) ;
  • Lee, Kuem-Ju (Department of Pharmacology, Korea University College of Medicine) ;
  • Shin, You-Chan (Department of Pharmacology, Korea University College of Medicine) ;
  • Choi, Song-hyen (Department of Pharmacology, Korea University College of Medicine) ;
  • Do, Eunju (Department of Pharmacology, Korea University College of Medicine) ;
  • Kim, Sangduk (Graduate School of Biomedical Sciences, Korea University College of Medicine) ;
  • Chun, Boe-Gwun (Department of Pharmacology, Korea University College of Medicine) ;
  • Lee, Min-Soo (Department of Psychiatry, Korea University College of Medicine) ;
  • Shin, Kyung-Ho (Department of Pharmacology, Korea University College of Medicine)
  • Received : 2004.08.28
  • Accepted : 2004.11.02
  • Published : 2005.02.28

Abstract

Stress is known to inhibit granule cell proliferation in the hippocampus. However, recent studies suggest that the commonly used dose of bromodeoxyuridine (BrdU) is insufficient to label all fractions of granule cells. Furthermore, stress-induced changes in BrdU availability may influence the labeling of newly born cells. To investigate whether changes in BrdU availability affect measurements of stress-induced granule cell proliferation, granule cell proliferation was assessed using injection of high doses of BrdU before and after restraint stress lasting 1 h. In addition, to determine whether stress-induced changes in plasma corticosterone levels were influenced by the BrdU, time-dependent changes in plasma corticosterone levels over 2 h after BrdU injection were compared with total accumulated plasma corticosterone levels [as determined by areas under the curve (AUC)]. Restraint stress significantly reduced the numbers of BrdU-labeled cells and clusters in the granule cell layer (GCL) of rats that received BrdU after stress, and decreases of similar magnitude were observed when the rats were given BrdU before stress. BrdU injection enhanced the stress-induced plasma corticosterone response, but there was no difference between the mean AUCs of plasma corticosterone levels of animals injected with BrdU before or after stress. These observations suggest that restraint stress decreases granule cell proliferation, and that this may be influenced by the extent and duration of plasma corticosterone increases rather than by changes in the availability of BrdU.

Keywords

Acknowledgement

Supported by : Ministry of Health and Welfare

References

  1. Brown, J., Cooper-Kuhn, C. M., Kempermann, G., Van Praag, H., Winkler, J., et al. (2003) Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis. Eur. J. Neurosci. 17, 2042-2046 https://doi.org/10.1046/j.1460-9568.2003.02647.x
  2. Cameron, H. A., Tanapat, P., and Gould, E. (1997) Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway. Neuroscience 82, 349-354 https://doi.org/10.1016/S0306-4522(97)00303-5
  3. Cameron, H. A. and McKay, R. D. (2001) Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J. Comp. Neurol. 435, 406-417 https://doi.org/10.1002/cne.1040
  4. Choi, Y. S., Lee, M. Y., Sung, K. W., Jeong S. W., Choi, J. S., et al. (2003) Regional differences in enhanced neurogenesis in the dentate gyrus of adult rats after transient forebrain ischemia. Mol. Cells 16, 232-238
  5. Eisch, A. J. and Nestler, E. J. (2002) To be or not to be: adult neurogenesis and psychiatry. Clin. Neurosci. Res. 2, 93-108 https://doi.org/10.1016/S1566-2772(02)00011-7
  6. Eisch, A. J., Barrot, M., Schad, C. A., Self, D. W., and Nestler, E. J. (2000) Opiates inhibit neurogenesis in the adult rat hippocampus. Proc. Natl. Acad. Sci. USA 97, 7579-7584
  7. Endo, Y., Nishimura, J. I., Kobayashi, S., and Kimura, F. (1999) Chronic stress exposure influences local cerebral blood flow in the rat hippocampus. Neuroscience 93, 551-555 https://doi.org/10.1016/S0306-4522(99)00176-1
  8. Gould, E. and Gross, C. G. (2002) Neurogenesis in adult mammals: some progress and problems. J. Neurosci. 22, 619-623
  9. Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A., and Fuchs, E. (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J. Neurosci. 17, 2492-2498
  10. Gould, E., Tanapat, P., McEwen, B. S., Flugge, G., and Fuchs, E. (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc. Natl. Acad. Sci. USA 95, 3168-3171
  11. Gould, E., Reeves, A. J., Fallah, M., Tanapat, P., Gross, C. G., et al. (1999) Hippocampal neurogenesis in adult Old World primates. Proc. Natl. Acad. Sci. USA 96, 5263-5267
  12. Kempermann, G., Kuhn, H. G., and Gage, F. H. (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386, 493-495 https://doi.org/10.1038/386493a0
  13. Kempermann, G. and Gage, F. H. (2000) Neurogenesis in the adult hippocampus. Novartis Found. Symp. 231, 220-235;discussion 235-241, 302-226
  14. Malberg, J. E., Eisch, A. J., Nestler, E. J., and Duman, R. S. (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci. 20, 9104-9110
  15. Mandyam, C. D., Norris, R. D., and Eisch, A. J. (2004) Chronic morphine induces premature mitosis of proliferating cells in the adult mouse subgranular zone. J. Neurosci. Res. 76, 783-794 https://doi.org/10.1002/jnr.20090
  16. Nowakowski, R. S., Lewin, S. B., and Miller, M. W. (1989) Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population. J. Neurocytol. 18, 311-318 https://doi.org/10.1007/BF01190834
  17. Paxinos, G. and Watson, C. (1997) The Rat Brain in Stereotaxic Coordinates, 3rd edition, Academic Press, Inc., San Diego
  18. Pham, K., Nacher, J., Hof, P. R., and McEwen, B. S. (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur. J. Neurosci. 17, 879-886 https://doi.org/10.1046/j.1460-9568.2003.02513.x
  19. Sharma, H. S., Cervos-Navarro, J., and Dey, P. K. (1991) In80 Stress-induced Decreases in New Granule Cell Proliferation creased blood-brain barrier permeability following acute short-term swimming exercise in conscious normotensive young rats. Neurosci. Res. 10, 211-221 https://doi.org/10.1016/0168-0102(91)90058-7
  20. Sharma, H. S., Westman, J., Navarro, J. C., Dey, P. K., and Nyberg, F. (1995) Probable involvement of serotonin in the increased permeability of the blood-brain barrier by forced swimming. An experimental study using Evans blue and 131Isodium tracers in the rat. Behav. Brain Res. 72, 189-196 https://doi.org/10.1016/0166-4328(96)00170-2
  21. Shors, T. J., Miesegaes, G., Beylin, A., Zhao, M., Rydel, T., et al. (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410, 372-376 https://doi.org/10.1038/35066584
  22. Tanapat, P., Galea, L. A., and Gould, E. (1998) Stress inhibits the proliferation of granule cell precursors in the developing dentate gyrus. Int. J. Dev. Neurosci. 16, 235-239 https://doi.org/10.1016/S0736-5748(98)00029-X
  23. Tanapat, P., Hastings, N. B., Reeves, A. J., and Gould, E. (1999) Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J. Neurosci. 19, 5792-5801
  24. Tanapat, P., Hastings, N. B., Rydel, T. A., Galea, L. A., and Gould, E. (2001) Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormonedependent mechanism. J. Comp. Neurol. 437, 496-504 https://doi.org/10.1002/cne.1297
  25. Vollmayr, B., Simonis, C., Weber, S., Gass, P., and Henn, F. (2003) Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biol. Psychiatry 54, 1035-1040 https://doi.org/10.1016/S0006-3223(03)00527-4