Skip to main content

Advertisement

Log in

Maternal Alcohol Consumption Increases Sphingosine Levels in the Brains of Progeny Mice

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The effect of ‘binge’ alcohol upon sphingolipid metabolism in the fetal alcohol syndrome (FAS) was examined in pregnant mice (C57BL/6J) by administering a single dose of alcohol during the third trimester (gestational day 15–16). The control mice were administered a sucrose solution of equal caloric value. Brains from progeny at postnatal days 5, 15, 21 and 30 were dissected into three regions, and sphingolipid concentrations of the brain regions were determined including assay of monoglycosylceramide, ceramide, sphingosine and sphingomyelin. We found that a single dose of ethanol induces an elevation of sphingosine (2–3.5-fold) in the brain of progeny. The level of brain ceramide at a dose of 1.5 g/kg was significantly higher than control. Alcohol consumption during pregnancy induces neuronal loss in progeny brains. Our result suggests that the elevation of sphingosine in progeny brain induced by maternal alcohol consumption may be responsible for observed neuronal loss in FAS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Jones KL, Smith DW (1973) Recognition of the fetal alcohol syndrome in early infancy. Lancet 2:999–1001

    Article  CAS  PubMed  Google Scholar 

  2. Jones KL, Smith DW, Ulleland CN et al (1973) Patterns of malformations in offspring of chronic alcoholic mothers. Lancet 1:1267–1271

    Article  CAS  PubMed  Google Scholar 

  3. Randall CL (1987) Alcohol as a teratogen: A decade of research in review. Alcohol Alcohol 1:125–132

    CAS  Google Scholar 

  4. Abel EL, Bush R, Dinetcheff BA (1981) Exposure of rats to alcohol in utero alters drug sensitivity in adulthood. Science 212:1531–1533

    Article  CAS  PubMed  Google Scholar 

  5. Barnes DE, Walker DW (1981) Prenatal ethanol exposure permanently reduces the number of pyramidal neurons in rat hippocampus. Dev Brain Res 227:333–340

    Article  CAS  Google Scholar 

  6. Hungund BL, Ross DC, Gokhale VS (1994) Ganglioside GM1 reduces fetal alcohol effects in rat pups exposed to ethanol in utero. Alcohol Clin Exp Res 18:1248–1251

    Article  CAS  PubMed  Google Scholar 

  7. Lancaster FE (1994) Alcohol and white matter development - a Review. Alcoholism Clin Exp Res 18:644–647

    Article  CAS  Google Scholar 

  8. Phillips SC, Cragg BG (1982) A change in susceptibility of rat Purkinje cells to damage by alcohol during fetal, neonatal, and adult life. Neuropathol Appl Neurobiol 8:441–454

    CAS  PubMed  Google Scholar 

  9. Chen W-J A, Maier SE, West JR (1996) Toxic effects of ethanol on the fetal brain. In: Deitrich RA, Erwin VG (eds) Pharmacological effects of ethanol on the nervous system. CRC Press Inc., New York, pp 343–361

    Google Scholar 

  10. Bonthius DJ, West JR (1990) Alcohol-induced neuronal loss in developing rats: increased brain-damage with binge exposure. Alcohol Clin Exp Res 14:107–118

    Article  CAS  PubMed  Google Scholar 

  11. Cragg BG, Phillips SC (1985) Natural loss of Purkinje cells during development and increased loss with alcohol. Brain Res 325:151–160

    Article  CAS  PubMed  Google Scholar 

  12. Kotch LE, Sulik KK (1992) Experimental fetal alcohol syndrome: Proposed pathogenic basis for a variety of associated facial and brain anomalies. Am J Med Genet 44:168–172

    Article  CAS  PubMed  Google Scholar 

  13. Miller M (1995) Effect of pre- or postnatal exposure to ethanol on the total number of neurons in the principal sensory nucleus of the trigeminal nerve: Cell proliferation and neuronal death. Alcohlism Clin Exp Res 19:1359–1363

    Article  CAS  Google Scholar 

  14. West JR, Hamre KM, Cassell MD (1986) Effects of ethanol exposure during the third trimester equivalent on neuron number in rat hippocampus and dentate gyrus. Alcohol Clin Exp Res 10:190–197

    Article  CAS  PubMed  Google Scholar 

  15. Yanai J. Wakim S (1985) Comparison of the effects of barbiturate and ethanol given to neonates on the cerebellar morphology. Acta Anat 123:145–147

    Article  Google Scholar 

  16. Becker HC, Diaz-Granados J, Randall CL (1996) Teratogenesis actions of ethanol in the mouse: a minireview. Pharmacol Biochem Behav 55:501–513

    Article  CAS  PubMed  Google Scholar 

  17. Cioclia AA, Gautieri RF (1988) Teratogenic and behavioral anomalies induced by acute exposure of mice to ethanol and their possible relation to fetal brain synthesis. Pharmaceut Res 5:447–452

    Article  Google Scholar 

  18. Padmananabhan R, Muawad WMRA (1985) Encephaly and axial skeletal dysmorphogenesis induced by acute doses of ethanol in mouse fetuses. Drug Alcohol Dep 16:215–227

    Article  Google Scholar 

  19. Sulik KK, Johnston MC, Webb MA (1981) Fetal alcohol syndrome: embryogenesis in a mouse model. Science 214:936–938

    Article  CAS  PubMed  Google Scholar 

  20. Webster WS, Walsh DA, McEwen SE et al (1983) Some teratogenic properties of ethanol and acetaldehyde in C57BL/6J mice: Implications for the study of fetal alcohol syndrome. Teratology 27:231–243

    Article  CAS  PubMed  Google Scholar 

  21. Wainwright P, Fritz G (1985) Effect of moderate prenatal ethanol exposure on postnatal brain and behavioral development in BALB/c mice. Exp Neurol 89:237–249

    Article  CAS  PubMed  Google Scholar 

  22. Blass JP (1970) Fatty acid compositions of cerebrosides in microsomes and myelin of mouse brain. J Neurochem 17:545–551

    Article  CAS  PubMed  Google Scholar 

  23. Luse SA (1956) Formation of myelin in the CNS of mice and rats as studied with electron microscopy. J Biophys Biochem Cytol 2:777–782

    Article  CAS  PubMed  Google Scholar 

  24. Inoue Y, Nakamura R, Kikoshiba K et al (1981) Fine structure of the central myelin sheath in the myelin deficient mutant shiverer mouse, with special reference to the pattern of myelin formation by oligodendroglia. Brain Res 219:85–95

    Article  CAS  PubMed  Google Scholar 

  25. Verity C (2000) Of flies, mice and men. Dev Child Neurol 42:723

    Article  CAS  Google Scholar 

  26. Wang FD, Bian W, Kong LW et al (2001) Maternal zinc deficiency impairs brain nestin expression in prenatal and postnatal mice. Cell Res 11:135–141

    Article  CAS  PubMed  Google Scholar 

  27. Williams PL, Hall SM (1970) In vivo observations on matured myelinated nerve fibers of the mouse. J Anat 107:31–36

    CAS  PubMed  Google Scholar 

  28. Abel EL, Riley EP (1986) Studies of prenatal alcohol exposure: methodological considerations. In: West JR (ed) Alcohol and brain development. Oxford University Press, New York, pp 105–119

    Google Scholar 

  29. Atchley WR, Wei R, Crenshaw P (2000) Cellular consequences in the brain and liver of age-specific selection for rate of development in mice. Genetics 155:1347–1357

    CAS  PubMed  Google Scholar 

  30. Hogan EL, Greenfield S (1984) Animal models of genetic disorders of myelin. In: Morell P (ed) Myelin. Plenum Press, New York, pp 489–534

  31. Acampora D, Mazan S, Avantaggiato V et al (1996) Epilepsy and brain abnormalities in mice lacking the Otx 1 gene. Nat Genet 14:218–222

    Article  CAS  PubMed  Google Scholar 

  32. Heintz N (2000) One-hit neuronal death. Nature 406:137–139

    Article  CAS  PubMed  Google Scholar 

  33. Coetzee T, Dupree JL, Popko B (1998) Demyelination and altered expression of myelin-associated glycoprotein isoforms in the central nervous system of galactolipid-deficient mice. J Neurosci Res 54:613–622

    Article  CAS  PubMed  Google Scholar 

  34. Dewachter I, van Dorpe J, Smeijers L et al (2000) Aging increased amyloid peptide and caused amyloid plaques in brain of old APP/V7171 transgenic mice by a different mechanism than mutant presenilin 1. J Neurosci 20:6452–6458

    CAS  PubMed  Google Scholar 

  35. Heintz N (2001) BAC to the future: the use of bac transgenic mice for neuroscience research. Nature Rev Neurosci 2:861–870

    Article  CAS  Google Scholar 

  36. Kuo M, Crawford E, Mullan M et al (2000) Elevated A beta and apolipoprotein E in A betaPP transgenic mice and its relationship to amyloid accumulation in Alzheimer’s disease. Mol Med 6:430–439

    CAS  PubMed  Google Scholar 

  37. Miyakawa T, Yagi T, Kitazawa H et al (1997) Fyn-kinase as a determinant of ethanol sensitivity: relation to NMDA-receptor function. Science 278:698–701

    Article  CAS  PubMed  Google Scholar 

  38. Chin JH, Parsons LM, Goldstein DB (1978) Increased cholesterol content of erythrocyte and brain membranes in ethanol tolerant mice. Biochim Biophys Acta 513:358–363

    Article  CAS  PubMed  Google Scholar 

  39. Goldstein DB, Chin J, McComb JA et al (1986) Chronic effects of alcohols on mouse membranes. In: Begleiter H (ed) Biological effects of alcohols on mouse membranes. Plenum Press, New York, pp 184–203

    Google Scholar 

  40. Gustavsson L, Alling C (1989) Effects of chronic ethanol exposure on fatty acids of rat brain glycerophospholipids. Alcohol 6:139–146

    Article  CAS  PubMed  Google Scholar 

  41. Prasad VVTS (1992) Effect of prenatal and postnatal exposure to ethanol on rat central nervous system gangliosides and glycosidases. Lipids 27:344–348

    Article  CAS  PubMed  Google Scholar 

  42. Gnaedinger JM, Noronha AB, Druse MJ (1984) Myelin gangliosides in developing rats: the influence of maternal ethanol consumptions. J Neurochem 42:1281–1285

    Article  CAS  PubMed  Google Scholar 

  43. Prasad VVTS (1989) Maternal alcohol consumption and undernutrition in the rat: effects on gangliosides and their catabolizing enzymes in the CNS of rat newborn. Neurochem Res 14:1081–1088

    Article  CAS  PubMed  Google Scholar 

  44. Prasad VVTS (1993) Alterantions and recovery of rat brain gangliosides and glycosidases following long-term exposure to alcohol and rehabilitation during development. Brain Res 610:75–81

    Article  CAS  PubMed  Google Scholar 

  45. Olney JW, Tenkova T, Dikranian K et al (2002) Ethanol-induced apoptotic neurodegeneration in the developing C57BL/6 mouse brain. Brain Res Dev Brain Res 133:115–126

    Article  CAS  PubMed  Google Scholar 

  46. Olney JW, Wozniak DE, Jetovic-Todorovic V et al (2001) Glutamate signaling and the fetal alcohol syndrome. Ment Retard Dev Disabil Res Rev 7:267–275

    Article  CAS  PubMed  Google Scholar 

  47. Hannun YA (1994) The sphingomyelin cycle and the second messenger function of ceramide. J Biol Chem 269:3125–3128

    CAS  PubMed  Google Scholar 

  48. Hannun YA, Bell RM (1989) Function of sphingolipid and sphingolipid products in cellular regulation. Science 243:500–507

    Article  CAS  PubMed  Google Scholar 

  49. Spiegel S, Olivera A, Carlson RO (1993) The role of sphingosine in cell growth regulation and transmembrane signaling. Adv Lipid Res 235:105–129

    Google Scholar 

  50. Bieberich E, Mackinnon S, Silva J et al (2003) Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide. J Cell Biol 162:469–479

    Article  CAS  PubMed  Google Scholar 

  51. Nudelman ED, Levery SB, Igarashi Y et al (1992) Plasmalopsychosine, a novel plasmal (fatty aldehyde) conjugate of psychosine with cyclic acetal linkage: isolation and characterization from human brain white matter. J Biol Chem 267:11007–11016

    CAS  PubMed  Google Scholar 

  52. Bejaoui K, Wu C, Scheffler MD et al (2001) SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat Genet 27:261–262

    Article  CAS  PubMed  Google Scholar 

  53. Dawkins JL, Hulme DJ, Brahmbhatt SB et al (2001) Nucleotide, OMIM Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet 27:309–312

    Article  CAS  PubMed  Google Scholar 

  54. Aniker J, Chun J (2004) Lysophospholipid G protein coupled receptors. J Biol Chem 279:20555–20558

    Article  CAS  Google Scholar 

  55. Dasgupta S, Hogan EL (2001) Chromatographic resolution and quantitative assay of CNS tissue sphingoids and sphingolipids. J Lipid Res 42:301–308

    CAS  PubMed  Google Scholar 

  56. Merrill AH Jr, Wang E, Mullins RE et al (1988) Quantitation of free sphingosine in liver by high-performance chromatography. Anal Biochem 171:373–381

    Article  CAS  PubMed  Google Scholar 

  57. Igishu H, Suzuki K (1984) Analysis of galactosylsphingosine (psychosine) in the brain. J Lipid Res 25:1000–1006

    Google Scholar 

  58. Saito T, Hakomori S-I (1971) Quantitative isolation of total glycosphingolipids from animal cells. J Lipid Res 12:257–259

    CAS  PubMed  Google Scholar 

  59. Samson HH (1986) Microcephaly and fetal alcohol syndrome. Human and animal studies. In: West JR (ed) Alcohol and brain development. Oxford University Press, New York, pp 167–183

    Google Scholar 

  60. West JR (1987) Fetal alcohol-induced brain damage and the problem of determining temporal vulnerability: a review. Alcohol and Drug Res 7:423–441

    CAS  Google Scholar 

  61. Dasgupta S, Levery SB, Hogan EL (2002) 3-O-acetyl-sphingosine-series myelin glycolipids: characterization of novel 3-O-acetyl-sphingosine galactosylceramide. J Lipid Res 43:751–761

    CAS  PubMed  Google Scholar 

  62. Benion B, Dasgupta S, Hogan EL et al (2007) Characterization of novel myelin components, 3-O-Acetyl sphingosine galactosylceramides by electrospray ionizations Q-TOF-MS and MS-CID-MS of Li+ adducts. J Mass Spec 42:598–620

    Article  CAS  Google Scholar 

  63. Dasgupta S, Everhart MB, Bhat N et al (1997) Monoglycosylceramide in rat brain: occurrence, molecular expression and developmental variation. Dev Neurosci 13:367–375

    Google Scholar 

  64. Fang Y, Wu G, Xie X et al (2000). Endogenous GM1 ganglioside of the plasma membrane promotes neuritogenesis by two mechanisms. Neurochem Res 25:931–940

    Article  CAS  PubMed  Google Scholar 

  65. Farooqui T, Franklin T, Pearl DK et al (1997) Ganglioside GM1 enhances induction by nerve growth factor of a putative dimer of TrkA. J Neurochem 68:2348–2355

    Article  CAS  PubMed  Google Scholar 

  66. Igarashi Y, Hakomori S-I, Toyokuni T et al (1989) Effect of chemically well-defined sphingosine and its N-methyl derivatives on protein kinase c and src kinase activities. Biochemistry 28:6796–6800

    Article  CAS  PubMed  Google Scholar 

  67. Hakomori S-I (1990) Bifunctional role of glycosphingolipids: modulators for transmembrane signaling and mediator for cellular interactions. J Biol Chem 265:18713–18716

    CAS  PubMed  Google Scholar 

  68. Ohta H, Sweeney EA, Masamune A et al (1995) Induction of apoptosis by sphingosine in human leukomic HL-60 cells: a possible endogenous modulator of apoptotic DNA fragmentation occurring during phorbol ester-induced diffenrentiation. Cancer Res 551:691–697

    Google Scholar 

  69. Li Z, Lin H, Zhu Y et al (2001) Disruption of cell cycle kinetics and cyclin-dependent kinase system by ethanol in cultured cerebellar granule progenitors. Brain Res Dev Brain Res 132:47–58

    Article  CAS  PubMed  Google Scholar 

  70. de la Monte SM, Wands JR (2002) Chronic gestational exposure to ethanol impairs insulin-stimulated survival and mitochondrial function in cerebellar neurons. Cell Mol Life Sci 59:882–889

    Article  PubMed  Google Scholar 

  71. Menegola E, Broccia ML, Di Renzo F et al (2001) Acetaldyhyde in vitro exposure and apoptosis: a possible mechanism of teratogenesis. Alcohol 23:35–39

    Article  CAS  PubMed  Google Scholar 

  72. Han JY, Joo Y, Kim YS et al (2005) Ethanol induces cell death by activating caspase-3 in the rat cerebral cortex. Mol Cells 20:189–195

    CAS  PubMed  Google Scholar 

  73. Akbar M, Baik J, Calderon F et al (2006) Ethanol promotes neuronal apoptosis by inhibiting phosphotidylserine accumulation J Neurosci Res 83:432–440

    Article  CAS  PubMed  Google Scholar 

  74. Joshi S, Guleria RS, Pan J et al (2006) Ethanol impairs Rho GTPase signaling and differentiation of cerebellar granule neurons in a rodent model of fetal alcohol syndrome. Cell Mol Life Sci 63:2859–2870

    Article  CAS  PubMed  Google Scholar 

  75. Chu J, Tong M, de la Monte SM (2007) Chronic ethanol exposure causes mitochondrial dysfunction and oxidative stress in immature central nervous system neurons. Acta Neuropathol (Berlin) 113:659–673

    Article  CAS  Google Scholar 

  76. Gorod B (1997) Sphingoid bases in CNS development Thesis dissertation for HS graduation and Governor’s School for Science and Mathematics, SC

  77. Saito M, Saito M, Cooper TB et al (2005) Ethanol-induced changes in the content of triglycerides, ceramides, and glucosylceramides in cultured neurons. Alcohol Clin Exp Res 29:1374–1383

    Article  CAS  PubMed  Google Scholar 

  78. Napier JA, Michaelson LV, Dunn TM (2002) A new class of lipid desaturase central to sphingolipid biosynthesis and signaling. Trends Plant Sci 7:475–478

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

We thank Prof. W.O. Boggan, Department of Psychiatry, Medical University of South Carolina, for helpful consultation and suggestions regarding this work. The technical assistance of Ms. Elaine Terry is gratefully acknowledged. This work was supported by a grant from NIH/NIAAA AA11865.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Dasgupta.

Additional information

Special issue in honor of Naren Banik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dasgupta, S., Adams, J.A. & Hogan, E.L. Maternal Alcohol Consumption Increases Sphingosine Levels in the Brains of Progeny Mice. Neurochem Res 32, 2217–2224 (2007). https://doi.org/10.1007/s11064-007-9445-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-007-9445-3

Keywords

Navigation