MorphologyMorphologyМорфология1026-35432949-2556Eco-Vector39876910.17816/morph.398769ArticlesСтатьиReview ArticleTHE EFFECTS OF ALCOHOL ON THE DEVELOPING BRAINВЛИЯНИЕ АЛКОГОЛЯ НА РАЗВИВАЮЩИЙСЯ МОЗГZimatkinS. M.ЗиматкинСергей Михайлович

кафедра гистологии, цитологии и эмбриологии

zimatkin@grsmu.byBon’Ye. I.БоньЕлизавета Игоревна

кафедра гистологии, цитологии и эмбриологии

Grodno State Medical UniversityГродненский государственный медицинский университет150420141452VOL 145, NO2 (2014)ТОМ 145, №2 (2014)798809052023Copyright ©; 2014, Eco-VectorCopyright ©; 2014, Эко-Вектор2014Eco-VectorЭко-Векторhttps://j-morphology.com/1026-3543/article/view/398769

In the review the literature data on the effect of alcohol on the developing brain of human and animals are summarized. The information is presented on the neuroimaging, histological, cellular and molecular-genetic disturbances in the brain in fetal alcohol syndrome and following exposure to alcohol during the early postnatal period. The structural developmental abnormalities of the different parts of the brain, disorders of neurogenesis and neuronal apoptosis, changes in metabolism, receptors and secondary signals system of neurons are described. Prenatal alcohol exposure causes significant, various long-term disturbances of the brain structures at the organ, tissue, cellular and subcellular level, which may lay in the basis of the observed neurological, behavioral and metal disorders.

В обзоре обобщены данные литературы о влиянии алкоголя на развивающийся головной мозг человека и животных. Приведены сведения о нейровизуальных, гистологических, клеточных и молекулярно-генетических нарушениях в мозгу при фетальном алкогольном синдроме и воздействии алкоголя в раннем постнатальном периоде. Описаны структурные аномалии развития различных отделов мозга, нарушения нейрогенеза и апоптоз нейронов, изменения их метаболизма, рецепторов, системы вторичных посредников. Антенатальное воздействие алкоголя вызывает значительные, разнообразные и долговременные нарушения головного мозга на органном, тканевом, клеточном и субклеточном уровнях, которые могут лежать в основе наблюдаемых неврологических, поведенческих и психических расстройств.

brainfetal alcohol syndromemorphological disordersголовной мозгфетальный алкогольный синдромморфологические нарушенияАртюхина Н. И. Влияние употребления алкоголя самцами и самками крыс на структуру головного мозга потомства. В кн.: Алкоголизм и наследственность: Материалы междунар. симпоз., М., Наука, 1986, с. 30-33.Артюхина Н. И. и Ноздрачева Л. В. Нарушение структурнофункциональной организации митохондрий коры головного мозга белых крыс вследствие антенатальной алкогольной интоксикации. М., 1988, деп. в ВИНИТИ 8.88, № 8475.Бояджиева Н. Изучение влияния комбинированного применения метронидазола и алкоголя на развитие плода у крыс. Экспер. мед. морфол., 1986, № 2, с. 31-35.Дробленков А. В. и Карелина Н. Р. Усиление запрограммированной гибели и дегенеративное изменение нейронов мезокортико-лимбической дофаминергической системы как возможная причина врожденной алкогольной зависимости. Морфология, 2012, т. 141, вып. 1, с. 16-22.Зиматкин С. М. Альдегиддегидрогеназы мозга и их роль в патогенезе алкоголизма. Гродно, изд. ГрГМУ, 2008.Зиматкин С. М. и Лис Р. Е. Активность альдегиддегидрогеназы мозга крысы в онтогенезе. Арх. анат., 1990, т. 98, вып. 5, с. 27-33.Казакова П. Б. и Конокоитина Г. Ф. Гистологические и цитохимические изменения коры мозга потомства алкоголизированных животных. Журн. неврапатол. и психиатр., 1987, № 12, с. 1862-1865.Ковецкий Н. С., Солонский А. В. и Моховиков А. Н. Нейроморфологическое и электронно-микроскопическое исследование головного мозга эмбрионов, полученных от больных алкоголизмом матерей. В кн.: Алкоголизм. М., 1988, с. 76-80.Коновалов Г. Н., Ковец Н. С., Солонский А. В. и Моховиков А. Н. Нарушения развития головного мозга эмбрионов, полученных от злоупотреблявших алкоголем матерей. Журн. невропатол. и психиатр., 1988, т. 88, № 7, с. 60-66.Малахова Ж. Л. Клинико-патогенетические основы фетального алкогольного синдрома у детей: Автореф. дис. … канд. мед. наук. Екатеринбург, 2012.Попова Э. Н. Ультраструктура нейронов сенсомоторной коры у потомства крыс, получавших алкоголь во время беременности. Арх. анат., 1988, т. 94, вып. 3, с. 5-10.Попова Э. Н. Ультраструктура мозга, алкоголь и потомство. М., Научный мир, 2010.Разводовский Ю. Е. Медико-социальные аспекты алкоголизма. Гродно, изд. ГрГМУ, 2005.Сванидзе И. К., Мусеридзе Д. П., Дидимова Е. В. и др. Нарушение нейрогенеза корковых и подкорковых структур лимбической системы головного мозга крыс при формировании плодного алкогольного синдрома. Морфология, 2012, т. 141, вып. 2, с. 18-22.Смольникова Н. М., Скосырева А. М., Попова Э. Н. и Стрекалова С. Н. Антенатальное воздействие алкоголя на морфофункциональное развитие центральной нервной системы. Акуш. и гин., 1985, № 4, с. 61-64.Фрумкина Л. Е. Влияние хронической алкогольной интоксикации на структурную организацию хвостатого ядра их потомства. Арх. анат., 1985, т. 88, вып. 3, с. 26-33.Худоерков Р. М. и Цой Ю. Г. Влияние внутриутробной алкогольной интоксикации на постнатальное развитие нейронов коры головного мозга крыс (цитохимическое исследование). Сб. науч. трудов Ин-та мозга АМН СССР, 1987, № 16, с. 170-172.Akers K. G., Kushner S. A., Leslie A. T. et al. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice. Mol. Brain, 2011, v. 4, p. 29.Alfonso-Loeches S. and Guerri C. Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain. Crit. Rev. Clin. Lab. Sci., 2011, v. 48, p. 19-47.Alvares M. R. and Stone D. I. Hypoploidy and hyperplasia in the developing brain exposed to alcohol in utero. Teratology, 1988, v. 3, p. 233-238.Aronne M. P. Effects of prenatal ethanol exposure on rat brain radial glia and neuroblast migration. Exp. Neurol., 2011, v. 229, p. 364-371.Autti-Rämö I., Autti T., Korkman M. et al. MRI findings in children with school problems who had been exposed prenatally to alcohol. Dev. Med. Child. Neurol., 2002, v. 44, № 2, p. 98-106.Balaraman S., Winzer-Serhan U. H. and Miranda R. C. Opposing actions of ethanol and nicotine on micrornas are mediated by nicotinic acetylcholine receptors in fetal cerebral cortical-derived neural progenitor cells. Alcohol. Clin. Exp. Res., 2012, v. 36, p. 1669-1677.Balaszczuk V., Bender C., Pereno G. L. and Beltramino C. A. Alcohol-induced neuronal death in central extended amygdala and pyriform cortex during the postnatal period of the rat. Int. J. Dev. Neurosci., 2011, v. 29, № 7, p. 33-42.Bjorkquist O. A., Fryer S. L., Reiss A. L. et al. Cingulate gyrus morphology in children and adolescents with fetal alcohol spectrum disorders. Psychiatry Res., 2010, v. 181, № 2, p. 101-107.Bonthius D. J. and West J. R. Permanent neuronal deficits in rats exposed to alcohol during the brain growth spurt. Teratology, 1991, v. 44, № 2, p. 147-163.Chen S. and Charness M. E. Ethanol disrupts axon outgrowth stimulated by netrin-1, GDNF, and L1 by blocking their convergent activation of Src family kinase signaling. J. Neurochem., 2012, v. 123, p. 602-612.Chen W. J., Berryhill E. C. and West J. R. Zinc supplementation does not attenuate alcohol-induced cerebellar Purkinje cell loss during the brain growth spurt period. Alcohol. Clin. Exp. Res., 2001, v. 25, p. 600-605.Chikhladze R. T., Ramishvili N. S., Tsagareli Z. G. and Kikalishvili N. O. The spectrum of hemispheral cortex lesions in intrauterine alcoholic intoxication. Georgian Med. News, 2011, v. 192, p. 81-87.Clarren S. K., Astley S. J., Bowden D. M. et al. Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly doses of ethanol during gestation. Alcohol. Clin. Exp. Res., 1990, v. 14, № 5, p. 674-683.De la Monte S. M. and Wands J. R. Role of central nervous system insulin resistance in fetal alcohol spectrum disorders. J. Popul. Ther. Clin. Pharmacol., 2010, v. 17, № 3, p. 390-404.Dikranian K., Qin Y. Q., Labruyere J. et al. Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures. Brain Res. Dev. Brain Res., 2005, v. 155, № 1, p. 1-13.Dursun I., Jakubowska-Doğru E., van der List D. et al. Effects of early postnatal exposure to ethanol on retinal ganglion cell morphology and numbers of neurons in the dorsolateral geniculate in mice. Alcohol. Clin. Exp. Res., 2011, v. 35, № 11, p. 2063-2074.Elia M., Striano P., Fichera M. et al. 6q terminal deletion syndrome associated with a distinctive EEG and clinical pattern: a report of five cases. Epilepsia, 2006, v. 47, № 5, p. 830-838.Fabregues I., Ferrer I. and Gairi J. M. Effects of prenatal exposure to ethanol on the maturation of the pyramidal neurons in the cerebral cortex of the guinea pig: a quantitative Golgi study. Neuropathol. Appl. Neurobiol., 1985, v. 2, p. 291-298.Farber N. B., Creeley C. E. and Olney J. W. Alcohol-induced neuroapoptosis in the fetal macaque brain. Neurobiol. Dis., 2010, v. 40, p. 200-206.Fernández-Jaén A., Fernández-Mayoralas D. M., Quiñones Tapia D. et al. Cortical thickness in fetal alcohol syndrome and attention deficit disorder. Pediatr. Neurol., 2011, v. 45, № 6, p. 387-391.Ghimire S. R., Saxena A. K., Rai D. and Dhungel S. Effect of maternal alcohol consumption on cerebellum of rat pups: a histological study. Nepal Med. Coll. J., 2009, v. 11, № 4, p. 268-271.Gressens P., Lammens M., Picard J. J. and Evrard P. Ethanol-induced disturbances of gliogenesis and neuronogenesis in the developing murine brain: an in vitro and in vivo immunohistochemical and ultrastructural study. Alcohol Alcohol., 1992, v. 27, № 3, p. 219-226.Guerri C., Pascual M. and Renau-Piqueras J. Glia and fetal alcohol syndrome. Neurotoxicology, 2001, v. 22, p. 593-599.Hammer R. P. and Sheibel A. B. Morphologycal evidence for a delay of neuronal maturation in fetal alcohol exposure. Exp. Neurol., 1981, v. 74, p. 582-596.Klintsova A. Y., Helfer J. L., Calizo L. H. et al. Persistent impairment of hippocampal neurogenesis in young adult rats following early postnatal alcohol exposure. Alcohol. Clin. Exp. Res., 2007, v. 31, № 12, p. 2073-2082.Lawrence R. C., Otero N. K. and Kelly S. J. Selective effects of perinatal ethanol exposure in medial prefrontal cortex and nucleus accumbens. Neurotoxicol. Teratol., 2012, v. 34, p. 128-135.Lee Y., Rowe J., Eskue K. et al. Alcohol exposure on postnatal day 5 induces Purkinje cell loss and evidence of Purkinje cell degradation in lobule I of rat cerebellum. Alcoholism, 2008, v. 42, № 4, p. 295-302.Lewandowska E., Stępień T., Wierzba-Bobrowicz T. et al. Alcohol-induced changes in the developing cerebellum. Ultrastructural and quantitative analysis of neurons in the cerebellar cortex. Folia Neuropathol., 2012, v. 50, № 4, p. 397-406.Livy D. J., Miller E. K., Maier S. E. and West J. R. Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the developing rat hippocampus. Neurotoxicol. Teratol., 2003, v. 25, № 4, p. 447-458.Maier S. E. and West J. R. Regional differences in cell loss associated with binge-like alcohol exposure during the first two trimesters equivalent in the rat. Alcoholism, 2001, v. 23, № 1, p. 49-57.Miki T.S., Harris J., Wilce P.A. et al. Effects of alcohol exposure during early life on neuron numbers in the rat hippocampus. I. Hilus neurons and granule cells. Hippocampus, 2003, v. 13, № 3, p. 388-398.Miki T., Yokoyama T., Sumitani K. et al. Ethanol neurotoxicity and dentate gyrus development. Congenit. Anom. (Kyoto), 2008, v. 48, № 3, p. 110-117.Miller M. W. Effects of alcohol on the generation and migration of cerebral cortical neurons. Science, 1986, v. 233, p. 1308-1311.Miller M. W. Migration of Cortical Neurons is Altered by Gestational Exposure to Ethanol. Alcohol. Clin. Exp. Res., 1993, v. 17, p. 304-314.Miller M. W. and Nowakowski R. S. Effect of prenatal exposure to ethanol on the cell cycle kinetics and growth fraction in the proliferative zones of fetal rat cerebral cortex. Alcohol. Clin. Exp. Res., 1991, v. 15, p. 229-232.Minciacchi D., Granato A., Santarelli M. and Sbriccoli A. Modifications of thalamo-cortical circuitry in rats prenatally exposed to ethanol. Neuroreport, 1993, v. 4, № 4, p. 415-418.Miranda R. C. MicroRNAs and fetal brain development: implications for ethanol teratology during the second trimester period of neurogenesis. Front. Genet., 2012, v. 3, p. 70-77.Moore D. B., Madorsky I., Paiva M. and Barrow Heaton M. Ethanol exposure alters neurotrophin receptor expression in the rat central nervous system: effects of neonatal exposure. J. Neurobiol., 2004, v. 60, № 1, p. 114-126.Nardelli A., Lebel C., Rasmussen C. et al. Extensive deep gray matter volume reductions in children and adolescents with fetal alcohol spectrum disorders. Alcohol. Clin. Exp. Res., 2011, v. 35, № 8, p. 1404-1417.Nokelainen P., Heiskala H., Raininko R. et al. Two brothers with macrocephaly, progressive cerebral atrophy and abnormal white matter, severe mental retardation, and Lennox-Gastaut spectrum type epilepsy: an inherited encephalopathy of childhood. Am. J. Med. Genet., 2001, v. 103, № 3, p. 198-206.Norman A. L., Crocker N., Mattson S. N. and Riley E. P. Neuroimaging and fetal alcohol spectrum disorders. Dev. Disabil. Res. Rev., 2009, v. 15, № 3, p. 209-217.Parnell S. E., O’Leary-Moore S. K., Godin E. A. et al. Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 8. Alcohol. Clin. Exp. Res., 2009, v. 33, № 6, p. 1001-1011.Ramadoss J., Lunde E. R., Chen W. J. et al. Temporal vulnerability of fetal cerebellar Purkinje cells to chronic binge alcohol exposure: ovine model. Alcohol. Clin. Exp. Res., 2007, v. 31, p. 1738-1745.Riley E. P., Infante M. A. and Warren K. R. Fetal alcohol spectrum disorders: an overview. Neuropsychol. Rev., 2011, v. 21, p. 73-80.Roebuck T. M., Mattson S. N. and Riley E. P. Interhemispheric transfer in children with heavy prenatal alcohol exposure. Alcohol. Clin. Exp. Res., 2002, v. 26, p. 1863-1871.Rosman N. P. and Malone M. J. An experimental study of fetal alcohol syndrome. Neurology, 1976, v. 26, p. 365-366.Roussotte F. F., Sulik K. K., Mattson S. N. et al. Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders. Hum. Brain Mapp., 2012, v. 33, № 4, p. 920-937.Samorajski T., Lancaster F. and Wiggins R. C. Fetal ethanol exposure: a morphometric analysis of myelination in the optic nerve. Dev. Neurosc., 1986, v. 4, p. 369-374.Sawant O. B., Lunde E. R., Washburn S. E. et al. Different patterns of regional Purkinje cell loss in the cerebellar vermis as a function of the timing of prenatal ethanol exposure in an ovine model. Neurotoxicol. Teratol., 2013, v. 35, p. 7-13.Schambra U.B, Lauder J. M. and Petrusz P. Development of neurotransmitter systems in the mouse embryo following acute ethanol exposure: a histological and immunocytochemical study. Dev. Neurosc., 1990, v. 8, p. 507-522.Siebert J. R., Astley S. J. and Clarren S. K. Holoprosencephaly in a fetal macaque (Macaca nemestrina) following weekly exposure to ethanol. Teratology, 1991, v. 44, p. 29-36.Spottiswoode B. S., Meintjes E. M., Anderson A. W. et al. Diffusion tensor imaging of the cerebellum and eyeblink conditioning in fetal alcohol spectrum disorder. Alcohol. Clin. Exp. Res., 2011, v. 35, № 12, p. 2174-2183.Sreenathan R. N., Padmanabhan R. and Singh S. Teratogenic effects of acetaldehyde in the rat. Drug Alcohol. Depend., 1982, v. 9, p. 339-350.Swayze V. W., Johnson V. P., Hanson J. W. et al. Magnetic resonance imaging of brain anomalies in fetal alcohol syndrome. Pediatrics, 1997, v. 99, p. 232-240.Tenkova T., Young C. and Olney J. W. Ethanol-induced apoptosis in the developing visual system during synaptogenesis. Inves. Ophthalmol. Vis. Sci., 2003, v. 44, p. 2809-2817.Toesca A., Giannetti S. and Granato A. Overexpression of the p75 neurotrophin receptor in the sensori-motor cortex of rats exposed to ethanol during early postnatal life. Neurosci. Lett., 2003, v. 342, p. 89-92.Tran T. D. and Kelly S. J. Critical periods for ethanol-induced cell loss in the hippocampal formation. Neurotoxicol. Teratol., 2003, v. 25, № 5, p. 519-528.Tsai G. and Coyle J. T. The role of glutamatergic neurotransmission in the pathophysiology of alcoholism. Ann. Rev. Med., 1998, v. 49, p. 173-184.Vallés S., Sancho-Tello M., Miñana R. et al. Glial fibrillary acidic protein expression in rat brain and in radial glia culture is delayed by prenatal ethanol exposure. J. Neurochem., 1996, v. 67, № 6, p. 2425-2433.Vangipuram S. D. and Lyman W. D. Ethanol alters cell fate of fetal human brain-derived stem and progenitor cells. Alcohol. Clin. Exp. Res., 2010, v. 34, p. 1574-1583.Wainright P. and Gagnon M. Moderate prenatal ethanol exposure interacts with strain in affecting brain development in BALB/c and C57BL/6 mice. Exp. Neurol., 1985, v. 88, p. 84-94.Ward G. R. and Wainwright P. E. Effects of prenatal stress and ethanol on cerebellar fiber tract maturation in B6D2F2 mice: an image analysis study. Neurotoxicology, 1991, v. 12, p. 665-676.Wierzba-Bobrowicz T., Lewandowska E., Stępień T. and Szpak G. M. Differential expression of calbindin D28k, calretinin and parvalbumin in the cerebellum of pups of ethanol-treated female rats. Folia Neuropathol., 2011, v. 49, № 1, p. 47-55.Wilson D. A., Peterson J., Basavaraj B. S. and Saito M. Local and regional network function in behaviorally relevant cortical circuits of adult mice following postnatal alcohol exposure. Alcohol. Clin. Exp. Res., 2011, v. 35, № 11, p. 1974-1984.Woodson P. and Ritchey S. Effects of maternal alcohol consumption of fetal brain cell number and cell size. Nutr. Repts. Int., 1979, v. 20, p. 225-228.Wozniak J. R., Mueller B. A., Muetzel R. L. et al. Inter-hemispheric functional connectivity disruption in children with prenatal alcohol exposure. Alcohol. Clin. Exp. Res., 2011, v. 35, № 5, p. 849-861.Yang Y., Roussotte F., Kan E. et al. Abnormal cortical thickness alterations in fetal alcohol spectrum disorders and their relationships with facial dysmorphology. Cereb. Cortex, 2012, v. 22, № 5, p. 1170-1179.Zhou F. C., Sari Y., Powrozek T. et al. Moderate alcohol exposure compromises neural tube midline development in prenatal brain. Brain Res. Dev. Brain Res., 2003, v. 144, № 1, p 43-55.Zhou F. C., Sari Y., Zhang J. K. et al. Prenatal alcohol exposure retards the migration and development of serotonin neurons in fetal C57BL mice. Brain Res. Dev. Brain Res., 2001, v. 126, № 2, p. 147-155.