Alterations of c-Fos mRNA Expression in Hypothalamic-Pituitary-Adrenal Axis and Various Brain Regions Induced by Intrathecal Single and Repeated Substance P Administrations in Mice

  • Choi, Seong-Soo (Department of Pharmacology, College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Lee, Han-Kyu (Department of Pharmacology, College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Shim, Eon-Jeong (Department of Pharmacology, College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Kwon, Min-Soo (Department of Pharmacology, College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Seo, Young-Jun (Department of Pharmacology, College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Lee, Jin-Young (Department of Pharmacology, College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Suh, Hong-Won (Department of Pharmacology, College of Medicine and Institute of Natural Medicine, Hallym University)
  • Published : 2004.08.01

Abstract

The effect of substance P (Sub P) injected intrathecally (I.t.) on c-fos mRNA expression in vari-ous tissues was examined in the present study. We found that a single administration of Sub P(0.5 nM) caused an increase of the c-fos mRNA level in the hypothalamic-pituitary-adrenal(HPA) axis, hippocampus, and spinal cord. The time-course study showed that c-fos mRNA level was maximal at 10 min and began to decrease 30 min after the Sub P injection in all tis-sues, and the Sub P-induced increase of the c-fos mRNA level was returned to the control level 1 h after the injection. The kinetics of the c-fos mRNA expression in mice that were repeatedly injected with Sub P (every 30 min interval up to 4 times) were different in the HPA axis, hippocampus, and spinal cord. The increased c-fos mRNA level in the hypothalamus and the spinal cord induced by I.t. injected Sub P remained at a high level. In the pituitary gland, adrenal gland, and hippocampus, the increased level of c-fos mRNA expression gradually returned to the control level during the repeated substance P injections up to 4 times. Our results suggest that spinally injected Sub P-induced pain stress increases c-fos mRNA expres-sion in the spinal cord, hippocampus, and HPA axis. In mice repeatedly injected with Sub P, the kinetics of c-fos mRNA appear to be different varied from tissue to tissue.

Keywords

References

  1. Aloisi, A. M., Ceccarelli, I., and Herdegen, T., Gonadectomy and persistent pain differently affect hippocampal c-Fos expression in male and female rats. Neurosci. Lett., 281, 29-32 (2000) https://doi.org/10.1016/S0304-3940(00)00819-3
  2. Aloisi, A. M., Zimmermann, M., and Herdegen, T., Sex-dependent effects of formalin and restraint on c-Fos expression in the septum and hippocampus of the rat. Neuroscience, 81, 951-958 (1997) https://doi.org/10.1016/S0306-4522(97)00270-4
  3. Arenander, A. and de Vellis, J., Early response gene induction in astrocytes as a mechanism for encoding and intergrating neuronal signals. Prog. Brain Res., 94, 177-188 (1994) https://doi.org/10.1016/S0079-6123(08)61749-5
  4. Ceccarelli, I., Scaramuzzino, A., Aloisi, A. M., Effects of formalin pain on hippocampal c-Fos expression in male and female rats. Pharmacol. Biochem. Behav., 64, 797-802 (1999) https://doi.org/10.1016/S0091-3057(99)00145-8
  5. Chomczynski, P. and Sacchi, N., Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal. Biochem., 162, 156-159 (1987)
  6. Chung, K. M., Lee, K. C., Choi, S. S., and Suh, H. W., Differential roles of spinal cholera toxin- and pertussis toxin-sensitive G proteins in nociceptive responses caused by formalin, capsaicin, and substance P in mice. Brain Res. Bull., 54, 537-542 (2001) https://doi.org/10.1016/S0361-9230(01)00441-5
  7. Curran, T., Gordon, M. B., Rubino, K. L., and Sambucetti, L. C., lsolation and characterization of the c-fos(rat) cDNA and analysis of post-translational modification in vitro. Oncogene, 2, 79-84 (1987)
  8. Danielson, P. E., Forss-Petter, S., Brow, M. A., Calavetta, L., Douglass, J., Milner, R. J., and Sutcliffe, J. G., p1B15: a cDNA clone of the rat mRNA encoding cyclophilin. DNA, 7, 261-267 (1988) https://doi.org/10.1089/dna.1988.7.261
  9. Heughan, C. E., Allen, G. V., Chase, T. D., and Sawynok, J. Peripheral amitriptyline suppresses formalin-induced Fos expression in the rat spinal cord. Anesth. Analg., 94, 427-431 (2002) https://doi.org/10.1097/00000539-200202000-00038
  10. Huang, W. and Simpson, R. K. Jr., Noxious thermal stimulation of c-fos activity induced in rat lumbar spinal cord is reduced by AP-5 but not by glycine. Neurosci. Lett., 259, 1-4 (1999) https://doi.org/10.1016/S0304-3940(98)00895-7
  11. Hunskaar, S., Post, C., Fasmer, O. B., and Arwestrom, E., Intrathecal injection of capsaicin can be used as a behavioural nociceptive test in mice. Neuropharmacology, 25, 1149-1153 (1986) https://doi.org/10.1016/0028-3908(86)90163-2
  12. Hylden, J. L. and Wilcox, G. L., Intrathecal morphine in mice: a new technique. Eur. J. Pharmacol., 67, 313-316 (1980) https://doi.org/10.1016/0014-2999(80)90515-4
  13. Kopchik, T. T., Cullen, R., and Stacey, D. W., Rapid analysis of small nucleic acid samples by gel electrophoresis. Anal. Biochem., 115, 419-423 (1981) https://doi.org/10.1016/0003-2697(81)90027-0
  14. Lee, Y. W., Park, K. A., and Lee, W. T., Effects of MK-801 and morphine on spinal c-Fos expression during the develop-ment of neuropathic pain. Yonsei Med. J., 43, 370-376 (2002)
  15. Li, X. and Clark, J. D., Heme oxygenase inhibitors reduce formalin-induced Fos expression in mouse spinal cord tissue. Neuroscience, 105, 949-956 (2001) https://doi.org/10.1016/S0306-4522(01)00207-X
  16. Sheng, M. and Greenberg, M. E., The regulation and function of c-fos and other immediate early genes in the nerve system. Neuron, 4, 477-485 (1990)
  17. Siegan, J. B., Herzberg, U., Frydel, B. R., and Sagen, J., Adrenal medullary transplants reduce formalin-evoked c-fos expression in the rat spinal cord. Brain Res., 944, 174-183 (2002) https://doi.org/10.1016/S0006-8993(02)02742-7
  18. Takahashi, N., Hayano, T., and Suzuki, M., Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature, 337, 473-475 (1989) https://doi.org/10.1038/337473a0
  19. Todd, A. J., Puskar, Z., Spike, R. C., Hughes, C., Watt, C., and Forrest, L., Projection neurons in lamina I of rat spinal cord with the neurokinin 1 receptor are selectively innervated by substance p-containing afferents and respond to noxious stimulation. J. Neurosci., 22, 4103-4113 (2002)
  20. Zou, X., Lin, Q., and Willis, W. D., NMDA or non-NMDA receptor antagonists attenuate increased Fos expression in spinal dorsal horn GABAergic neurons after intradermal injection of capsaicin in rats. Neuroscience, 106, 171-182 (2001) https://doi.org/10.1016/S0306-4522(01)00175-0