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. 1997 Jul;191(Pt 1):49–56. doi: 10.1046/j.1469-7580.1997.19110049.x

Morphometric analysis of the postnatal mouse optic nerve following prenatal exposure to alcohol

Y Y DANGATA 1, M H KAUFMAN 1
PMCID: PMC1467658  PMID: 9279658

Abstract

Pregnant female mice were divided on day 12 post coitum into a control and an experimental group. The experimental group was given a single intraperitoneal dose of 0.015 ml/g body weight of 25% solution of alcohol in distilled water while the control group was exposed to a similar weight related dose of normal saline. The optic nerves were isolated from the offspring of both control and experimental groups at wk 2, 3 and 5 (i.e. during the juvenile period of postnatal development) and analysed by light and electron microscopy. Although in both groups the optic nerve grew in size rapidly during the period studied, the rate of growth in the experimental groups lagged behind that of the controls. The difference was initially significant but tailed off, so that by wk 5 it was no longer significant. The time of initial onset and progression of myelinogenesis in the optic nerve of alcohol exposed mice also lagged behind that of controls. In both groups the size distribution of the myelinated nerve fibres in the optic nerve was unimodal with a positive skewing for all ages. The spectrum of size distribution of the nerve fibres was, however, broader in controls than in the corresponding experimental groups. With increasing age the proportion of small and medium size fibres was greater in the experimental group than in the controls, while for the large diameter fibres the reverse was observed. It is suggested that this study may shed light on the teratogenic effect of ‘binge’ drinking during pregnancy and that it is the critical period when exposure occurs that is more important than the duration of administration.

Keywords: Morphometry, optic neuropathy, myelinogenesis, fetal alcohol syndrome

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Selected References

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  1. Abel E. L., Dintcheff B. A., Bush R. Effects of beer, wine, whiskey, and ethanol on pregnant rats and their offspring. Teratology. 1981 Apr;23(2):217–222. doi: 10.1002/tera.1420230206. [DOI] [PubMed] [Google Scholar]
  2. Ashwell K. W., Zhang L. L. Optic nerve hypoplasia in an acute exposure model of the fetal alcohol syndrome. Neurotoxicol Teratol. 1994 Mar-Apr;16(2):161–167. doi: 10.1016/0892-0362(94)90113-9. [DOI] [PubMed] [Google Scholar]
  3. Asou H., Hamada K., Miyazaki T., Sakota T., Hayashi K., Takeda Y., Marret S., Delpech B., Itoh K., Uyemura K. CNS myelinogenesis in vitro: time course and pattern of rat oligodendrocyte development. J Neurosci Res. 1995 Mar 1;40(4):519–534. doi: 10.1002/jnr.490400411. [DOI] [PubMed] [Google Scholar]
  4. Asou H., Hamada K., Uyemura K., Sakota T., Hayashi K. How do oligodendrocytes ensheath and myelinate nerve fibers? Brain Res Bull. 1994;35(4):359–365. doi: 10.1016/0361-9230(94)90114-7. [DOI] [PubMed] [Google Scholar]
  5. Black J. A., Foster R. E., Waxman S. G. Rat optic nerve: freeze-fracture studies during development of myelinated axons. Brain Res. 1982 Oct 28;250(1):1–20. doi: 10.1016/0006-8993(82)90948-9. [DOI] [PubMed] [Google Scholar]
  6. Chernoff G. F. The fetal alcohol syndrome in mice: an animal model. Teratology. 1977 Jun;15(3):223–229. doi: 10.1002/tera.1420150303. [DOI] [PubMed] [Google Scholar]
  7. Chernoff G. F. The fetal alcohol syndrome in mice: maternal variables. Teratology. 1980 Aug;22(1):71–75. doi: 10.1002/tera.1420220110. [DOI] [PubMed] [Google Scholar]
  8. Clarren S. K. Recognition of fetal alcohol syndrome. JAMA. 1981 Jun 19;245(23):2436–2439. [PubMed] [Google Scholar]
  9. Cohen A. I. Ultrastructural aspects of the human optic nerve. Invest Ophthalmol. 1967 Jun;6(3):294–308. [PubMed] [Google Scholar]
  10. Cook C. S., Nowotny A. Z., Sulik K. K. Fetal alcohol syndrome. Eye malformations in a mouse model. Arch Ophthalmol. 1987 Nov;105(11):1576–1581. doi: 10.1001/archopht.1987.01060110122045. [DOI] [PubMed] [Google Scholar]
  11. Dangata Y. Y., Findlater G. S., Dhillon B., Kaufman M. H. Morphometric study of the optic nerve of adult normal mice and mice heterozygous for the Small eye mutation (Sey/+). J Anat. 1994 Dec;185(Pt 3):627–635. [PMC free article] [PubMed] [Google Scholar]
  12. Dangata Y. Y., Findlater G. S., Kaufman M. H. Morphometric analysis of myelinated fibre composition in the optic nerve of adult C57BL and CBA strain mice and (C57BL x CBA) F1 hybrid: a comparison of interstrain variation. J Anat. 1995 Apr;186(Pt 2):343–348. [PMC free article] [PubMed] [Google Scholar]
  13. Dangata Y. Y., Findlater G. S., Kaufman M. H. Postnatal development of the optic nerve in (C57BL x CBA)F1 hybrid mice: general changes in morphometric parameters. J Anat. 1996 Aug;189(Pt 1):117–125. [PMC free article] [PubMed] [Google Scholar]
  14. Dentinger M. P., Barron K. D., Csiza C. K. Glial and axonal development in optic nerve of myelin deficient rat mutant. Brain Res. 1985 Oct 7;344(2):255–266. doi: 10.1016/0006-8993(85)90803-0. [DOI] [PubMed] [Google Scholar]
  15. Ehyai A., Freemon F. R. Progressive optic neuropathy and sensorineural hearing loss due to chronic glue sniffing. J Neurol Neurosurg Psychiatry. 1983 Apr;46(4):349–351. doi: 10.1136/jnnp.46.4.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. GYLLENSTEN L., MALMFORS T. Myelinization of the optic nerve and its dependence on visual function--a quantitative investigation in mice. J Embryol Exp Morphol. 1963 Mar;11:255–266. [PubMed] [Google Scholar]
  17. Garro A. J., McBeth D. L., Lima V., Lieber C. S. Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol Clin Exp Res. 1991 Jun;15(3):395–398. doi: 10.1111/j.1530-0277.1991.tb00536.x. [DOI] [PubMed] [Google Scholar]
  18. Gilliam D. M., Kotch L. E., Dudek B. C., Riley E. P. Ethanol teratogenesis in selectivity bred long-sleep and short-sleep mice: a comparison to inbred C57BL/6J mice. Alcohol Clin Exp Res. 1989 Oct;13(5):667–672. doi: 10.1111/j.1530-0277.1989.tb00402.x. [DOI] [PubMed] [Google Scholar]
  19. Herrmann J., Pallister P. D., Opitz J. M. Tetraectrodactyly and other skeletal manifestations in the fetal alcohol syndrome. Eur J Pediatr. 1980 May;133(3):221–226. doi: 10.1007/BF00496080. [DOI] [PubMed] [Google Scholar]
  20. Jones K. L., Smith D. W. Recognition of the fetal alcohol syndrome in early infancy. Lancet. 1973 Nov 3;302(7836):999–1001. doi: 10.1016/s0140-6736(73)91092-1. [DOI] [PubMed] [Google Scholar]
  21. Jones K. L., Smith D. W., Streissguth A. P., Myrianthopoulos N. C. Outcome in offspring of chronic alcoholic women. Lancet. 1974 Jun 1;1(7866):1076–1078. doi: 10.1016/s0140-6736(74)90555-8. [DOI] [PubMed] [Google Scholar]
  22. Jones K. L., Smith D. W., Ulleland C. N., Streissguth P. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet. 1973 Jun 9;1(7815):1267–1271. doi: 10.1016/s0140-6736(73)91291-9. [DOI] [PubMed] [Google Scholar]
  23. Kaufman M. Cephalic neurulation and optic vesicle formation in the early mouse embryo. Am J Anat. 1979 Aug;155(4):425–443. doi: 10.1002/aja.1001550403. [DOI] [PubMed] [Google Scholar]
  24. Kotch L. E., Dehart D. B., Alles A. J., Chernoff N., Sulik K. K. Pathogenesis of ethanol-induced limb reduction defects in mice. Teratology. 1992 Oct;46(4):323–332. doi: 10.1002/tera.1420460403. [DOI] [PubMed] [Google Scholar]
  25. Kronick J. B. Teratogenic effects of ethyl alcohol administered to pregnant mice. Am J Obstet Gynecol. 1976 Apr 1;124(7):676–680. doi: 10.1016/s0002-9378(16)33334-8. [DOI] [PubMed] [Google Scholar]
  26. Lancaster F. E., Mayur B. K., Patsalos P. N., Samorajski T., Wiggins R. C. The synthesis of myelin and brain subcellular membrane proteins in the offspring of rats fed ethanol during pregnancy. Brain Res. 1982 Mar 4;235(1):105–113. doi: 10.1016/0006-8993(82)90199-8. [DOI] [PubMed] [Google Scholar]
  27. Lancaster F. E., Phillips S. M., Patsalos P. N., Wiggins R. C. Brain myelination in the offspring of ethanol-treated rats: in utero versus lactational exposure by crossfostering offspring of control, pairfed and ethanol treated dams. Brain Res. 1984 Sep 10;309(2):209–216. [PubMed] [Google Scholar]
  28. Matheson D. F. Some quantitative aspects of myelination of the optic nerve in rat. Brain Res. 1970 Dec 1;24(2):257–269. doi: 10.1016/0006-8993(70)90105-8. [DOI] [PubMed] [Google Scholar]
  29. Matthews M. A., Duncan D. A quantitative study of morphological changes accompanying the initiation and progress of myelin production in the dorsal funiculus of the rat spinal cord. J Comp Neurol. 1971 May;142(1):1–22. doi: 10.1002/cne.901420102. [DOI] [PubMed] [Google Scholar]
  30. Mayhew T. M. An efficient sampling scheme for estimating fibre number from nerve cross sections: the fractionator. J Anat. 1988 Apr;157:127–134. [PMC free article] [PubMed] [Google Scholar]
  31. Mayhew T. M., Sharma A. K. Sampling schemes for estimating nerve fibre size. I. Methods for nerve trunks of mixed fascicularity. J Anat. 1984 Aug;139(Pt 1):45–58. [PMC free article] [PubMed] [Google Scholar]
  32. Mayhew T. M., Sharma A. K. Sampling schemes for estimating nerve fibre size. II. Methods for unifascicular nerve trunks. J Anat. 1984 Aug;139(Pt 1):59–66. [PMC free article] [PubMed] [Google Scholar]
  33. Michaelis E. K. Fetal alcohol exposure: cellular toxicity and molecular events involved in toxicity. Alcohol Clin Exp Res. 1990 Dec;14(6):819–826. doi: 10.1111/j.1530-0277.1990.tb01821.x. [DOI] [PubMed] [Google Scholar]
  34. Middaugh L. D., Boggan W. O. Postnatal growth deficits in prenatal ethanol-exposed mice: characteristics and critical periods. Alcohol Clin Exp Res. 1991 Dec;15(6):919–926. doi: 10.1111/j.1530-0277.1991.tb05189.x. [DOI] [PubMed] [Google Scholar]
  35. Miller M. W. Migration of cortical neurons is altered by gestational exposure to ethanol. Alcohol Clin Exp Res. 1993 Apr;17(2):304–314. doi: 10.1111/j.1530-0277.1993.tb00768.x. [DOI] [PubMed] [Google Scholar]
  36. Miller M. W., al-Rabiai S. Effects of prenatal exposure to ethanol on the number of axons in the pyramidal tract of the rat. Alcohol Clin Exp Res. 1994 Apr;18(2):346–354. doi: 10.1111/j.1530-0277.1994.tb00024.x. [DOI] [PubMed] [Google Scholar]
  37. Ng A. Y., Stone J. The optic nerve of the cat: appearance and loss of axons during normal development. Brain Res. 1982 Nov;281(3):263–271. doi: 10.1016/0165-3806(82)90125-0. [DOI] [PubMed] [Google Scholar]
  38. Padmanabhan R., Hameed M. S., Sugathan T. N. Effects of acute doses of ethanol on pre- and postnatal development in the mouse. Drug Alcohol Depend. 1984 Oct;14(2):197–208. doi: 10.1016/0376-8716(84)90045-0. [DOI] [PubMed] [Google Scholar]
  39. Parson S. H., Dhillon B., Findlater G. S., Kaufman M. H. Optic nerve hypoplasia in the fetal alcohol syndrome: a mouse model. J Anat. 1995 Apr;186(Pt 2):313–320. [PMC free article] [PubMed] [Google Scholar]
  40. Phillips D. E. Effects of limited postnatal ethanol exposure on the development of myelin and nerve fibers in rat optic nerve. Exp Neurol. 1989 Jan;103(1):90–100. doi: 10.1016/0014-4886(89)90190-8. [DOI] [PubMed] [Google Scholar]
  41. Phillips D. E., Krueger S. K. Effects of combined pre- and postnatal ethanol exposure (three trimester equivalency) on glial cell development in rat optic nerve. Int J Dev Neurosci. 1992 Jun;10(3):197–206. doi: 10.1016/0736-5748(92)90059-9. [DOI] [PubMed] [Google Scholar]
  42. Phillips D. E., Krueger S. K., Rydquist J. E. Short- and long-term effects of combined pre- and postnatal ethanol exposure (three trimester equivalency) on the development of myelin and axons in rat optic nerve. Int J Dev Neurosci. 1991;9(6):631–647. doi: 10.1016/0736-5748(91)90025-h. [DOI] [PubMed] [Google Scholar]
  43. Pinazo-Duran M. D., Renau-Piqueras J., Guerri C. Developmental changes in the optic nerve related to ethanol consumption in pregnant rats: analysis of the ethanol-exposed optic nerve. Teratology. 1993 Oct;48(4):305–322. doi: 10.1002/tera.1420480404. [DOI] [PubMed] [Google Scholar]
  44. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Schenker S., Becker H. C., Randall C. L., Phillips D. K., Baskin G. S., Henderson G. I. Fetal alcohol syndrome: current status of pathogenesis. Alcohol Clin Exp Res. 1990 Oct;14(5):635–647. doi: 10.1111/j.1530-0277.1990.tb01220.x. [DOI] [PubMed] [Google Scholar]
  46. Schwetz B. A., Smith F. A., Staples R. E. Teratogenic potential of ethanol in mice, rats and rabbits. Teratology. 1978 Dec;18(3):385–392. doi: 10.1002/tera.1420180313. [DOI] [PubMed] [Google Scholar]
  47. Tennekoon G. I., Cohen S. R., Price D. L., McKhann G. M. Myelinogenesis in optic nerve. A morphological, autoradiographic, and biochemical analysis. J Cell Biol. 1977 Mar;72(3):604–616. doi: 10.1083/jcb.72.3.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Umemori H., Sato S., Yagi T., Aizawa S., Yamamoto T. Initial events of myelination involve Fyn tyrosine kinase signalling. Nature. 1994 Feb 10;367(6463):572–576. doi: 10.1038/367572a0. [DOI] [PubMed] [Google Scholar]
  49. Warrington A. E., Barbarese E., Pfeiffer S. E. Differential myelinogenic capacity of specific developmental stages of the oligodendrocyte lineage upon transplantation into hypomyelinating hosts. J Neurosci Res. 1993 Jan;34(1):1–13. doi: 10.1002/jnr.490340102. [DOI] [PubMed] [Google Scholar]
  50. Webster W. S., Walsh D. A., McEwen S. E., Lipson A. H. Some teratogenic properties of ethanol and acetaldehyde in C57BL/6J mice: implications for the study of the fetal alcohol syndrome. Teratology. 1983 Apr;27(2):231–243. doi: 10.1002/tera.1420270211. [DOI] [PubMed] [Google Scholar]
  51. Zajac C. S., Abel E. L. Animal models of prenatal alcohol exposure. Int J Epidemiol. 1992;21 (Suppl 1):S24–S32. doi: 10.1093/ije/21.supplement_1.s24. [DOI] [PubMed] [Google Scholar]

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