Skip to main content
Log in

Alcohol deters the outgrowth of serotonergic neurons at midgestation

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

We have previously demonstrated that treatment of pregnant C57BL mice from gestation days 8 to 14 with alcohol with 20% ethanol-derived calories (EDC) reduced the number of serotonin (5-HT) neurons and retarded their migration in the fetal brains. In the present study, we obtained similar results with the use of 25% EDC and extended our previous findings by demonstrating that besides the alteration of the number of 5-HT neurons, prenatal alcohol exposure also affects their projecting fibers in their early development. Pregnant C57BL mice were divided into an alcohol-exposed (ALC) group given 25% EDC (4.49%, v/v), a pair-fed group to the ethanol-fed group (PF) and a chow-fed group (Chow). The PF and Chow groups served as controls. Our results showed that in the ALC group, when compared with the control groups, prenatal alcohol exposure with 25% EDC reduced the number of 5-HT-immunoreactive neurons in both the median and dorsal raphe, and the amount of 5-HT-immunoreactive fibers in the medial forebrain bundle (MFB). The diameter of the 5-HT-immunoreactive MFB was also reduced as a result of treatment. No significant differences of the above parameters were found between the PF and Chow groups. The previous and present work confirmed that alcohol reduces the normal formation and growth of 5-HT neurons in the midbrain. Furthermore, the projection of 5-HT fibers, in density as well as in distribution, is reduced in the major trajectory bundle. This may affect the amount of 5-HT fibers available to the forebrain. In light of the importance of the 5-HT system in brain development, alcohol may affect the growth of the forebrain through its effect on 5-HT signaling.

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.

Similar content being viewed by others

References

  1. Azmitia EC, Dolan K, Whitaker-Azmitia PM. S-100β but not NGF, EGF, insulin or calmodulin is a CNS serotonergic growth factor. Brain Res 516:354–356;1990.

    Article  PubMed  Google Scholar 

  2. Barron S, Gagnon WA, Mattson SN, Kotch LE, Meyer LS, Riley EP. The effects of prenatal alcohol exposure on odor associative learning in rats. Neurotoxicol Teratol 10:333–339;1988.

    PubMed  Google Scholar 

  3. Bauer-Moffett C, Altman J. Ethanol-induced reductions in cerebellar growth of infant rats. Exp Neurol 48:478–382;1975.

    Article  Google Scholar 

  4. Bauer-Moffett C, Altman J. The effects of ethanol chronically administered to preweanling rats on cerebellar development: A morphological study. Brain Res 119:249–268;1977.

    Article  PubMed  Google Scholar 

  5. Buznikov GA, Shmukler YB. Possible role of ‘prenervous’ neurotransmitters in cellular interactions of early embryogenesis: A hypothesis. Neurochem Res 6:55–68;1981.

    Article  PubMed  Google Scholar 

  6. Coles CD. Prenatal alcohol exposure and human development. In: Miller M, ed. Development of the Central Nervous System, Effects of Alcohol and Opiates. New York, Liss, 9–36;1992.

    Google Scholar 

  7. Detering N, Collins R, Hawkins RL, Ozand PT, Karahasan AM. The effects of ethanol on developing catecholamine neurons. Adv Exp Med Biol 132:721–727;1980.

    PubMed  Google Scholar 

  8. De Vitry F, Hamon M, Catelon J, Bubois M, Thibault J. Serotonin initiates and autoamplifies its own synthesis during mouse central nervous system development. Proc Natl Acad Sci USA 83:8629–8633;1986.

    Google Scholar 

  9. Druse MJ, Tajuddin N, Kuo A. Effects of in utero ethanol exposure on the developing dopaminergic system in rats. J Neurosci Res 27:233–240;1990.

    Article  PubMed  Google Scholar 

  10. Druse MJ, Kuo A, Tajuddin N. Effects of in utero ethanol exposure on the developing serotonergic system. Alcohol Clin Exp Res 15:678–684;1991.

    PubMed  Google Scholar 

  11. Elis J, Krsiak M, Poschlova N, Masek K. The effect of alcohol administration during pregnancy on the concentration of noradrenaline, dopamine and 5-hydroxytryptamine in the brain of offspring of mice. Act Nerv Sup (Praha) 18:220–221;1976.

    Google Scholar 

  12. Elis J, Krsiak M, Poschlova N. Effect of alcohol given at different periods of gestation on brain serotonin in offspring. Act Nerv Sup (Praha) 20:287–288;1978.

    Google Scholar 

  13. Emerit MB, Riad M, Hamon M. Trophic effects of neurotransmitters during brain maturation. Biol Neonate 62:193–201;1992.

    Google Scholar 

  14. Eriksen JL, Gillespie RA, Druse MJ. Effects of in utero ethanol exposure and maternal treatment with a 5-HT(1A) agonist on S100B-containing glial cells. Brain Res Dev Brain Res 121:133–143;2000.

    Article  PubMed  Google Scholar 

  15. Farr KL, Montany CY, Paxton LL, Savage DD. Prenatal ethanol exposure decreases hippocampal3H-vinylidene kainic acid binding in 45-day-old rats. Neurotoxicol Teratol 10:563–568;1989.

    Article  Google Scholar 

  16. Guerri C, Saez R, Sancho-Tello M, Martin de Aquilera E, Renau-Piqueras J. Ethanol alters astrocyte development: A study of critical periods using primary cultures. Neurochem Res 15:559–565;1990.

    Article  PubMed  Google Scholar 

  17. Hamon M, Bourgoin S, Chanez C, De Vitry F. Do serotonin and other neurotransmitters exert a trophic influence on the immature brain? In: Evrard P, Minkowski A, eds. Developmental Neurobiology. Nestlé Nutrition Workshop Series. New York, Raven Press, 12:171–183;1989.

    Google Scholar 

  18. Kelly GM, Druse MJ, Tonetti DA, Oden BG. Maternal ethanol consumption: Binding ofL-glutamate to synaptic membranes from whole brain, cortices, and cerebella of offspring. Exp Neurol 91:219–228;1986.

    Article  PubMed  Google Scholar 

  19. Kennedy LA, Mukerji S. Ethanol neurotoxicity. I. Direct effect on replicating astrocytes. Neurobehav Toxicol Teratol 8:11–15;1986.

    PubMed  Google Scholar 

  20. Kim J-A, Druse MJ. Protective effects of maternal buspirone treatment on serotonin reuptake sites in ethanol-exposed offspring. Dev Brain Res 92:190–198;1996.

    Article  Google Scholar 

  21. Konovalov HV, Kovetsky NS, Bobryshev YV, Ashwell KWS. Disorders of brain development in the progeny of mothers who used alcohol during pregnancy. Early Hum Dev 48:153–166;1997.

    Article  PubMed  Google Scholar 

  22. Kornguth SE, Rutledge JJ, Sunderland E, Siegel F, Carlson I, Smoliens J, Juhl U, Young B. Impeded cerebellar development and reduced serum thyroxin levels associated with fetal alcohol intoxication. Brain Res 177:347–366;1979.

    Article  PubMed  Google Scholar 

  23. Krsiak M, Elis J, Poschlova N, Masek K. Increased aggressiveness and lower brain serotonin levels in offspring of mice given alcohol during gestation. J Study Alcohol 38:1969–1704;1977.

    Google Scholar 

  24. Lauder JM. Ontogeny of the serotonergic system in the rat: Serotonin as a developmental signal. Ann NY Acad Sci 600:297–314;1990.

    PubMed  Google Scholar 

  25. Lauder JM. neurotransmitters as growth regulatory signals: Role of receptors and second messengers. Trends Neurosci 16:233–239;1993.

    Article  PubMed  Google Scholar 

  26. Lauder JM, Krebs H. Serotonin as a differentiation signal in early neurogenesis. Dev Neurosci 1:15–30;1978.

    PubMed  Google Scholar 

  27. Light KE, Serbus DC, Santiago M. Exposure of rats to ethanol from postnatal days 4 to 8: Alterations of cholinergic neurochemistry in the cerebral cortex and corpus striatum at day 20. Alcohol Clin Exp Res 13:29–35;1989.

    PubMed  Google Scholar 

  28. Liu JP, Lauder JM. S100β and insulin-like growth factor-II differentially regulate growth of developing serotonin and dopamine neurons in vitro. J Neurosci Res 33:248–256;1992.

    Article  PubMed  Google Scholar 

  29. Mattson SN, Riley EP, Jernigan TL, Ehlers CL, Delis DC, Jones KL, Stern C, Johnson KA, Hesselink JR, Bellugi U. Fetal alcohol syndrome: A case report of neuropsychological, MRI, and EEG assessment of two children. Alcohol Clin Exp Res 16:1001–1003;1992.

    PubMed  Google Scholar 

  30. Mattson SN, Riley EP, Jernigan TL, Garcia A, Kaneko WM, Ehlers CL, Jones KL. A decrease in the size of the basal ganglia following prenatal alcohol exposure: A preliminary report. Neurotoxicol Teratol 16:283–289;1994.

    Article  PubMed  Google Scholar 

  31. Mattson SN, Riley EP, Sowell ER, Jernigan TL, Sobel DF, Jones KL. A decrease in the size of the basal ganglia in children with fetal alcohol syndrome. Alcohol Clin Exp Res 20:1088–1093;1996.

    PubMed  Google Scholar 

  32. Paxinos G, Törk I, Tecott LH, Valentino KL. Atlas of the Developing Rat Brain. Academic Press, San Diego, 1991.

    Google Scholar 

  33. Rawat AK. Development of histaminergic pathways in brain as influenced by maternal alcoholism. Res Commun Chem Pathol Pharmacol 27:91–103;1990.

    Google Scholar 

  34. Renau-Piqueras J, Zaragoza R, De Paz P, Baguena-Cervella R, Megias L, Guerri C. Effects of prolonged ethanol exposure on the glial fibrillary acidic protein-containing intermediate filaments of astrocytes in primary culture: A quantitative immunofluorescence and immunogold electron microscopic study. J Histochem Cytochem 37:229–240;1989.

    PubMed  Google Scholar 

  35. Riikonen R, Salonen I, Partanen K, Verho S. Brain perfusion SPECT and MRI in foetal alcohol syndrome. Dev Med Child Neurol 41:652–659;1999.

    Article  PubMed  Google Scholar 

  36. Samson HH, Diaz J. Altered development of brain by neonatal ethanol exposure: Zinc levels during and after exposure. Alcohol Clin Exp Res 5:563–569;1981.

    PubMed  Google Scholar 

  37. Sari Y, Goodlett CR, Li TK, Zhou FC. Effects of fetal alcohol exposure on sizes and dimension of fetal forebrain in C57BL/6J mice. Abstr Soc Neurosci 29:441.1;1999.

    Google Scholar 

  38. Schambra UB, Lauder JM Petrusz P, Sulik KK. Development of neurotransmitter systems in the mouse embryo following acute ethanol exposure: A histological and immunocytochemical study. Int J Dev Neurosci 8:507–522;1990.

    Article  PubMed  Google Scholar 

  39. Serbus DC, Stull RE, Light KE. Neonatal ethanol exposure to rat pups: Resultant alterations of cortical muscarinic and cerebellar H1-histaminergic receptor binding dynamics. Neurotoxicology 7:257–278;1986.

    PubMed  Google Scholar 

  40. Sternberger LA. Immunocytochemistry, ed 2. New York, Wiley, 104–169;1979.

    Google Scholar 

  41. Streissguth AP, Martin JC. Prenatal effects of alcohol abuse in humans and laboratory animals. Kissin B, Begleiter H, eds. The Pathogenesis of Alcoholism. New York, Plenum Press, 539–589;1983.

    Google Scholar 

  42. Tajuddin NF, Druse MJ. In utero ethanol exposure decreased the density of serotonin neurons: Maternal ipsapirone treatment exerted a protective effect. Dev Brain Res 117:91–97;1999.

    Article  Google Scholar 

  43. Wallace JA, Lauder JM. Development of the serotonergic system in the rat embryo: An immunochemical study. Brain Res Bull 10:459–479;1983.

    Article  PubMed  Google Scholar 

  44. Whitaker-Azmitia PM, Azmitia EC. Astroglial 5-HT1A receptors S-100 beta in development and plasticity. Perspect Dev Neurobiol 2:2333–2338;1994.

    Google Scholar 

  45. Whitaker-Azmitia PM, Murphy R, Azmitia EC. Stimulation of astroglial 5-HT1A receptors releases the serotonergic growth factor, protein S-100, and alters astroglial morphology. Brain Res 528:155–158;1990.

    Article  PubMed  Google Scholar 

  46. Zafar H, Shelat SG, Redei E, Tejani-Butt S. Fetal alcohol exposure alters serotonin transporter sites in rat brain. Brain Res 856:184–192;2000.

    PubMed  Google Scholar 

  47. Zhou FC, Lumeng L, Li TK. Quantitative immunocytochemical evaluation of serotonergic innervation in alcoholic rat brain. Neurochemistry 26:135–143;1995.

    Article  Google Scholar 

  48. Zhou FC, Sari Y, Goodlett CR, Lumeng L, Li TK. Mouse model of neural tube defect after fetal alcohol exposure (abstract 149). Alcohol Clin Exp Res 23(suppl 5):30A;1999.

    Google Scholar 

  49. Zhou FC, Sari Y, Goodlett CR, Zhang JK, Li TK. Prenatal alcohol exposure retards the migration and reduces the number of 5-HT neurons in fetal C57BL/6 mice (abstract 150). Alcohol Clin Exp Res 23(suppl 5):30A;1999.

  50. Zhou FC, Sari Y, Zhang JK, Goodlett CR, Li TK. Prenatal alcohol exposure retards the migration and development of serotonin neurons in fetal C57BL/6J mice. Brain Res Dev, in press.

  51. Zhou FC, Sari Y, Zhang JK. Expression of serotonin transporter protein in developing rat brain. Brain Res Dev Brain Res 119:33–45;2000.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sari, Y., Powrozek, T. & Zhou, F.C. Alcohol deters the outgrowth of serotonergic neurons at midgestation. J Biomed Sci 8, 119–125 (2001). https://doi.org/10.1007/BF02255980

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02255980

Key words

Navigation