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. 1999 Jul;195(Pt 1):11–18. doi: 10.1046/j.1469-7580.1999.19510011.x

Mu opioid receptors in developing human spinal cord

SUBRATA BASU RAY 1,✉, SHASHI WADHWA 1
PMCID: PMC1467960  PMID: 10473288

Abstract

The distribution of mu opioid receptors was studied in human fetal spinal cords between 12–13 and 24–25 wk gestational ages. Autoradiographic localisation using [3H] DAMGO revealed the presence of mu receptors in the dorsal horn at all age groups with a higher density in the superficial laminae (I–II). A biphasic expression was noted. Receptor density increased in the dorsal horn, including the superficial laminae, between 12–13 and 16–17 wk. This could be associated with a spurt in neurogenesis. The density increased again at 24–25 wk in laminae I–II which resembled the adult pattern of distribution. A dramatic proliferation of cells was noted from the region of the ventricular zone between 16–17 and 24–25 wk. These were considered to be glial cells from their histological features. Mu receptor expression was noted over a large area of the spinal cord including the lateral funiculus at 24–25 wk. This may be due to receptor expression by glial cells. The study presents evidence of mu receptor expression by both neurons and glia during early development of human spinal cord.

Keywords: Neurogenesis, spinal cord, dorsal horn laminae, glial development

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Selected References

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  1. Bachevalier J., Ungerleider L. G., O'Neill J. B., Friedman D. P. Regional distribution of [3H]naloxone binding in the brain of a newborn rhesus monkey. Brain Res. 1986 Mar;390(2):302–308. doi: 10.1016/s0006-8993(86)80240-2. [DOI] [PubMed] [Google Scholar]
  2. Behar T., Schaffner A., Laing P., Hudson L., Komoly S., Barker J. Many spinal cord cells transiently express low molecular weight forms of glutamic acid decarboxylase during embryonic development. Brain Res Dev Brain Res. 1993 Apr 16;72(2):203–218. doi: 10.1016/0165-3806(93)90185-d. [DOI] [PubMed] [Google Scholar]
  3. Besse D., Lombard M. C., Zajac J. M., Roques B. P., Besson J. M. Pre- and postsynaptic distribution of mu, delta and kappa opioid receptors in the superficial layers of the cervical dorsal horn of the rat spinal cord. Brain Res. 1990 Jun 25;521(1-2):15–22. doi: 10.1016/0006-8993(90)91519-m. [DOI] [PubMed] [Google Scholar]
  4. Bijlani V., Rizvi T. A., Wadhwa S. Development of spinal substrate for nociception in man. NIDA Res Monogr. 1988;87:167–179. [PubMed] [Google Scholar]
  5. Charnay Y., Paulin C., Dray F., Dubois P. M. Distribution of enkephalin in human fetus and infant spinal cord: an immunofluorescence study. J Comp Neurol. 1984 Mar 1;223(3):415–423. doi: 10.1002/cne.902230307. [DOI] [PubMed] [Google Scholar]
  6. Choi B. H., Kim R. C. Expression of glial fibrillary acidic protein in immature oligodendroglia. Science. 1984 Jan 27;223(4634):407–409. doi: 10.1126/science.6197755. [DOI] [PubMed] [Google Scholar]
  7. Erdö S. L., Wolff J. R. Postnatal development of the excitatory amino acid system in visual cortex of the rat. Changes in uptake and levels of aspartate and glutamate. Int J Dev Neurosci. 1990;8(2):205–208. doi: 10.1016/0736-5748(90)90012-q. [DOI] [PubMed] [Google Scholar]
  8. Faull R. L., Villiger J. W. Opiate receptors in the human spinal cord: a detailed anatomical study comparing the autoradiographic localization of [3H]diprenorphine binding sites with the laminar pattern of substance P, myelin and nissl staining. Neuroscience. 1987 Feb;20(2):395–407. doi: 10.1016/0306-4522(87)90100-x. [DOI] [PubMed] [Google Scholar]
  9. Fields H. L., Heinricher M. M., Mason P. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci. 1991;14:219–245. doi: 10.1146/annurev.ne.14.030191.001251. [DOI] [PubMed] [Google Scholar]
  10. Gibson D. A., Vernadakis A. [3H]Etorphine binding activity in early chick embryos: brain and body tissue. Brain Res. 1982 May;256(1):23–29. doi: 10.1016/0165-3806(82)90093-1. [DOI] [PubMed] [Google Scholar]
  11. Gouardères C., Beaudet A., Zajac J. M., Cros J., Quirion R. High resolution radioautographic localization of [125I]FK-33-824-labelled mu opioid receptors in the spinal cord of normal and deafferented rats. Neuroscience. 1991;43(1):197–209. doi: 10.1016/0306-4522(91)90427-p. [DOI] [PubMed] [Google Scholar]
  12. Hammer R. P., Jr Mu-opiate receptor binding in the medial preoptic area is cyclical and sexually dimorphic. Brain Res. 1990 May 7;515(1-2):187–192. doi: 10.1016/0006-8993(90)90595-3. [DOI] [PubMed] [Google Scholar]
  13. Handa B. K., Land A. C., Lord J. A., Morgan B. A., Rance M. J., Smith C. F. Analogues of beta-LPH61-64 possessing selective agonist activity at mu-opiate receptors. Eur J Pharmacol. 1981 Apr 9;70(4):531–540. doi: 10.1016/0014-2999(81)90364-2. [DOI] [PubMed] [Google Scholar]
  14. Hauser K. F., McLaughlin P. J., Zagon I. S. Endogenous opioid systems and the regulation of dendritic growth and spine formation. J Comp Neurol. 1989 Mar 1;281(1):13–22. doi: 10.1002/cne.902810103. [DOI] [PubMed] [Google Scholar]
  15. Hauser K. F., Stiene-Martin A., Mattson M. P., Elde R. P., Ryan S. E., Godleske C. C. mu-Opioid receptor-induced Ca2+ mobilization and astroglial development: morphine inhibits DNA synthesis and stimulates cellular hypertrophy through a Ca(2+)-dependent mechanism. Brain Res. 1996 May 13;720(1-2):191–203. doi: 10.1016/0006-8993(96)00103-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hirano M., Goldman J. E. Gliogenesis in rat spinal cord: evidence for origin of astrocytes and oligodendrocytes from radial precursors. J Neurosci Res. 1988 Oct-Dec;21(2-4):155–167. doi: 10.1002/jnr.490210208. [DOI] [PubMed] [Google Scholar]
  17. Hohmann C. F., Brooks A. R., Coyle J. T. Neonatal lesions of the basal forebrain cholinergic neurons result in abnormal cortical development. Brain Res. 1988 Aug 1;470(2):253–264. doi: 10.1016/0165-3806(88)90244-1. [DOI] [PubMed] [Google Scholar]
  18. Honda C. N., Arvidsson U. Immunohistochemical localization of delta- and mu-opioid receptors in primate spinal cord. Neuroreport. 1995 May 9;6(7):1025–1028. doi: 10.1097/00001756-199505090-00019. [DOI] [PubMed] [Google Scholar]
  19. Insel T. R., Miller L. P., Gelhard R. E. The ontogeny of excitatory amino acid receptors in rat forebrain--I. N-methyl-D-aspartate and quisqualate receptors. Neuroscience. 1990;35(1):31–43. doi: 10.1016/0306-4522(90)90117-m. [DOI] [PubMed] [Google Scholar]
  20. Kar S., Quirion R. Neuropeptide receptors in developing and adult rat spinal cord: an in vitro quantitative autoradiography study of calcitonin gene-related peptide, neurokinins, mu-opioid, galanin, somatostatin, neurotensin and vasoactive intestinal polypeptide receptors. J Comp Neurol. 1995 Apr 3;354(2):253–281. doi: 10.1002/cne.903540208. [DOI] [PubMed] [Google Scholar]
  21. Kemp T., Spike R. C., Watt C., Todd A. J. The mu-opioid receptor (MOR1) is mainly restricted to neurons that do not contain GABA or glycine in the superficial dorsal horn of the rat spinal cord. Neuroscience. 1996 Dec;75(4):1231–1238. doi: 10.1016/0306-4522(96)00333-8. [DOI] [PubMed] [Google Scholar]
  22. Knapp P. E., Hauser K. F. mu-Opioid receptor activation enhances DNA synthesis in immature oligodendrocytes. Brain Res. 1996 Dec 16;743(1-2):341–345. doi: 10.1016/s0006-8993(96)01097-9. [DOI] [PubMed] [Google Scholar]
  23. Kornblum H. I., Hurlbut D. E., Leslie F. M. Postnatal development of multiple opioid receptors in rat brain. Brain Res. 1987 Dec 15;465(1-2):21–41. doi: 10.1016/0165-3806(87)90226-4. [DOI] [PubMed] [Google Scholar]
  24. Kornblum H. I., Loughlin S. E., Leslie F. M. Effects of morphine on DNA synthesis in neonatal rat brain. Brain Res. 1987 Jan;428(1):45–52. doi: 10.1016/0165-3806(87)90081-2. [DOI] [PubMed] [Google Scholar]
  25. Lauder J. M., Han V. K., Henderson P., Verdoorn T., Towle A. C. Prenatal ontogeny of the GABAergic system in the rat brain: an immunocytochemical study. Neuroscience. 1986 Oct;19(2):465–493. doi: 10.1016/0306-4522(86)90275-7. [DOI] [PubMed] [Google Scholar]
  26. Levison S. W., Goldman J. E. Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron. 1993 Feb;10(2):201–212. doi: 10.1016/0896-6273(93)90311-e. [DOI] [PubMed] [Google Scholar]
  27. Levitt P., Cooper M. L., Rakic P. Coexistence of neuronal and glial precursor cells in the cerebral ventricular zone of the fetal monkey: an ultrastructural immunoperoxidase analysis. J Neurosci. 1981 Jan;1(1):27–39. doi: 10.1523/JNEUROSCI.01-01-00027.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Magnan J., Lemay J., Tiberi M. Binding of the non-selective opioid [3H]etorphine in the human fetal central nervous system. Brain Res. 1988 Feb 1;466(2):300–303. doi: 10.1016/0165-3806(88)90057-0. [DOI] [PubMed] [Google Scholar]
  29. Nornes H. O., Das G. D. Temporal pattern of neurogenesis in spinal cord of rat. I. An autoradiographic study--time and sites of origin and migration and settling patterns of neuroblasts. Brain Res. 1974 Jun 14;73(1):121–138. doi: 10.1016/0006-8993(74)91011-7. [DOI] [PubMed] [Google Scholar]
  30. Owen A. D., Bird M. M. Role of glutamate in the regulation of the outgrowth and motility of neurites from mouse spinal cord neurons in culture. J Anat. 1997 Aug;191(Pt 2):301–307. doi: 10.1046/j.1469-7580.1997.19120301.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Seatriz J. V., Hammer R. P., Jr Effects of opiates on neuronal development in the rat cerebral cortex. Brain Res Bull. 1993;30(5-6):523–527. doi: 10.1016/0361-9230(93)90078-p. [DOI] [PubMed] [Google Scholar]
  32. Shaw C., Wilkinson M., Cynader M., Needler M. C., Aoki C., Hall S. E. The laminar distributions and postnatal development of neurotransmitter and neuromodulator receptors in cat visual cortex. Brain Res Bull. 1986 May;16(5):661–671. doi: 10.1016/0361-9230(86)90137-1. [DOI] [PubMed] [Google Scholar]
  33. Stiene-Martin A., Gurwell J. A., Hauser K. F. Morphine alters astrocyte growth in primary cultures of mouse glial cells: evidence for a direct effect of opiates on neural maturation. Brain Res Dev Brain Res. 1991 May 20;60(1):1–7. doi: 10.1016/0165-3806(91)90149-d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Taylor J., Docherty M., Gordon-Weeks P. R. GABAergic growth cones: release of endogenous gamma-aminobutyric acid precedes the expression of synaptic vesicle antigens. J Neurochem. 1990 May;54(5):1689–1699. doi: 10.1111/j.1471-4159.1990.tb01223.x. [DOI] [PubMed] [Google Scholar]
  35. Whitaker-Azmitia P. M. Role of serotonin and other neurotransmitter receptors in brain development: basis for developmental pharmacology. Pharmacol Rev. 1991 Dec;43(4):553–561. [PubMed] [Google Scholar]
  36. Xia Y., Haddad G. G. Ontogeny and distribution of opioid receptors in the rat brainstem. Brain Res. 1991 May 24;549(2):181–193. doi: 10.1016/0006-8993(91)90457-7. [DOI] [PubMed] [Google Scholar]
  37. Zagon I. S., McLaughlin P. J. Endogenous opioid systems regulate cell proliferation in the developing rat brain. Brain Res. 1987 May 26;412(1):68–72. doi: 10.1016/0006-8993(87)91440-5. [DOI] [PubMed] [Google Scholar]
  38. Zagon I. S., McLaughlin P. J. Neuronal cell deficits following exposure to methadone in rats. Experientia. 1982 Oct 15;38(10):1214–1216. doi: 10.1007/BF01959747. [DOI] [PubMed] [Google Scholar]

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