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Persistent neocortical astrogliosis in adult wistar rats following prenatal ethanol exposure

      Abstract

      Timed pregnant wistar rats were divided randomly into groups A and B (n=6) each and C (n=4). Group A received a daily ethanol dose of 5.8 g/kg body weight per day, at 16.00 h on days 9–12th of gestation by intragastric intubations. Group B was pair-fed along with the treated rats and received an isocaloric solution of sucrose to substitute for the ethanol in the experimental group, for the same duration, while group C received standard chow and water ad libitum. The adult offsprings at 42 days of age, (n=10) from each group were sacrificed by whole body perfusion-fixation, after anaesthesia by an overdose of penthotal intraperitoneally. Specimens of neocortical samples were processed routinely for paraffin embedding and sections of 6 μm thickness stained for neurohistology. Another set of specimens was cryosectioned at −23 °C after cryoprotection in 30% sucrose/PBS and evaluated for GFAP immunohistochemistry. The study showed a distortion of the microanatomy of the neocortex in the treatment group A, particularly of layer V pyramidal neurons, which revealed mostly pyknotic pyramidal neurons with broken dendrites, collapsed cell bodies, obliterated nuclei and nucleoli. No differences were found between the brains from rats in groups B and C. There were widespread focal areas of reactive astrogliosis, more prominent within the layer V. Astrocytes demonstrated highly stained GFAP-positive immunoreactivity with heavy fibrillary processes in the neocortex of group A offsprings compared to the controls. The sub-pial regions were, however, sparse. In conclusion, this study confirms the hypothesis that microanatomical and microchemical changes following prenatal ethanol exposure persist into adulthood in rats.

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      References

        • American Academy of Pediatrics: Committee on Substance Abuse and Committee on Children with Disabilities
        Fetal alcohol syndrome and alcohol-related neurodevelopmental disorders.
        Pediatrics. 2000; 106: 358-361
        • Jones K.L.
        • Smith D.W.
        Recognition of the fetal alcohol syndrome.
        Lancet. 1973; 2: 999-1001
        • Zhou F.C.
        • Sari Y.
        • Powrozek T.
        • Goodlett C.R.
        • Li T.K.
        Moderate alcohol exposure compromises neural tube midline development in prenatal brain.
        Brain Res Dev Brain Res. 2003; 144: 43-55
        • McGoey T.N.
        • Reynolds J.N.
        • Brien J.F.
        Chronic prenatal ethanol exposure-induced decrease of guinea pig hippocampal CA1 pyramidal cell and cerebellar Purkinje cell density.
        Can J Physiol Pharmacol. 2003; 81: 476-484
        • Guerri C.
        Mechanisms involved in central nervous system dysfunctions induced by prenatal ethanol exposure.
        Neurotox Res. 2002; 4: 327-335
        • Berman R.F.
        • Hannigan J.H.
        Effects of prenatal alcohol exposure on the hippocampus: spatial behavior, electrophysiology, and neuroanatomy.
        Hippocampus. 2000; 10: 94-110
        • Mattson S.N.
        • Schoenfeld A.M.
        • Riley E.P.
        Teratogenic effects of alcohol on brain and behavior.
        Alcohol Res Health. 2001; 25: 185-191
        • Kelly S.J.
        • Day N.
        • Streissguth A.P.
        Effects of prenatal alcohol exposure on social behavior in humans and other species.
        Neurotoxicol Teratol. 2000; 22: 143-149
        • Sampson P.D.
        • Streissguth A.P.
        • Bookstein F.L.
        • Barr H.M.
        On categorizations in analyses of alcohol teratogenesis.
        Environ Health Perspect. 2000; 108: 421-428
        • Autti-Ramo I.
        Twelve-year follow-up of children exposed to alcohol in utero.
        Dev Med Child Neurol. 2000; 42: 406-411
        • Miller M.W.
        Expression of transforming growth factor-beta in developing rat cerebral cortex: effects of prenatal exposure to ethanol.
        J Comp Neurol. 2003; 460: 410-424
        • Miller M.W.
        Migration of cortical neurons is altered by gestational exposure to ethanol.
        Alcohol Clin Exp Res. 1993; 17: 304-314
        • Maier S.E.
        • Chen W.J.
        • West J.R.
        Prenatal binge-like alcohol exposure alters neurochemical profiles in fetal rat brain.
        Pharmacol Biochem Behav. 1996; 55: 521-529
        • Chaudhuri J.D.
        Alcohol and the developing fetus—a review.
        Med Sci Monit. 2000; 6: 1031-1041
        • Puri R.K.
        • Reynolds J.N.
        • Brien J.F.
        Effects of chronic prenatal ethanol exposure on NMDA receptor number and affinity for [(3)H]MK-801 in the cerebral cortex of the young postnatal and adult guinea-pig.
        Reprod Fertil Dev. 2003; 15: 207-214
        • Li Z.
        • Miller M.W.
        • Luo J.
        Effects of prenatal exposure to ethanol on the cyclin-dependent kinase system in the developing rat cerebellum.
        Brain Res Dev Brain Res. 2002; 139: 237-245
        • De Vito W.J.
        • Xhaja K.
        • Stone S.
        Prenatal alcohol exposure increases TNFalpha-induced cytotoxicity in primary astrocytes.
        Alcohol. 2000; 21: 63-71
        • Goodlett C.R.
        • Leo J.T.
        • O'Callaghan J.P.
        • Mahoney J.C.
        • West J.R.
        Transient cortical astrogliosis induced by alcohol exposureduring the neonatal brain growth spurt in rats.
        Brain Res Dev Brain Res. 1993; 72: 85-97
        • Goodlett C.R.
        • Peterson S.D.
        • Lundahl K.R.
        • Pearlman A.D.
        Binge-like alcohol exposure of neonatal rats via intragastric intubation induces both Purkinje cell loss and cortical astrogliosis.
        Alcohol Clin Exp Res. 1997; 21: 1010-1017
        • Komatsu S.
        • Sakata-Haga H.
        • Sawada K.
        • Hisano S.
        • Fukui Y.
        Prenatal exposure to ethanol induces leptomeningeal heterotopia in the cerebral cortex of the rat fetus.
        Acta Neuropathol (Berl). 2001; 101: 22-26
        • Guerri C.
        • Pascual M.
        • Renau-Piqueras J.
        Glia and fetal alcohol syndrome.
        Neurotoxicology. 2001; 22: 593-599
        • Guerri C.
        • Renau-Piqueras J.
        Alcohol, astroglia, and brain development.
        Mol Neurobiol. 1997; 15: 65-81
        • Guerri C.
        • Saez R.
        • Portoles M.
        • Renau-Piqueras J.
        Derangement of astrogliogenesis as a possible mechanism involved in alcohol-induced alterations of central nervous system development.
        Alcohol Alcohol Suppl. 1993; 2: 203-208
        • Valles S.
        • Sancho-Tello M.
        • Minana R.
        • Climent E.
        • Renau-Piqueras J.
        • Guerri C.
        Glial fibrillary acidic protein expression in rat brain and in radial glia culture is delayed by prenatal ethanol exposure.
        J Neurochem. 1996; 67: 2425-2433
        • Valles S.
        • Pitarch J.
        • Renau-Piqueras J.
        • Guerri C.
        Ethanol exposure affects glial fibrillary acidic protein gene expression and transcription during rat brain development.
        J Neurochem. 1997; 69: 2484-2493
        • Sbriccoli A.
        • Carretta D.
        • Santarelli M.
        • Granato A.
        • Minciacchi D.
        An optimised procedure for prenatal ethanol exposure with determination of its effects on central nervous system connections.
        Brain Res Brain Res Protoc. 1999; 3: 264-269
        • Gibson M.A.
        • Butters N.S.
        • Reynolds J.N.
        • Brien J.F.
        Effects of chronic prenatal ethanol exposure on locomotor activity, and hippocampal weight, neurons, and nitric oxide synthase activity of the young postnatal guinea pig.
        Neurotoxicol Teratol. 2000; 22: 183-192
        • Heaton M.B.
        • Mitchell J.J.
        • Paiva M.
        • Walker D.W.
        Ethanol-induced alterations in the expression of neurotrophic factors in the developing rat central nervous system.
        Brain Res Dev Brain Res. 2000; 121: 97-107
        • Ikonomidou C.
        • Bittigau P.
        • Ishimaru M.J.
        • Wozniak D.F.
        • Koch C.
        • Genz K.
        • et al.
        Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome.
        Science. 2000; 287: 1056-1060
        • Ishimaru M.J.
        • Ikonomidou C.
        • Tenkova T.I.
        • Der T.C.
        • Dikranian K.
        • Sesma M.A.
        • Olney JW
        Distinguishing excitotoxic from apoptotic neurodegeneration in the developing rat brain.
        J Comp Neurol. 1999; 408: 461-476
        • Diaz-Granados J.L.
        • Spuhler-Phillips K.
        • Lilliquist M.W.
        • Amsel A.
        • Leslie S.W.
        Effects of prenatal and early postnatal ethanol exposure on [3H]MK-801 binding in rat cortex and hippocampus.
        Alcohol Clin Exp Res. 1997; 21: 874-881
        • Hamby-Mason R.
        • Chen J.J.
        • Schenker S.
        • Perez A.
        • Henderson G.I.
        Catalase mediates acetaldehyde formation from ethanol in fetal and neonatal rat brain.
        Alcohol Clin Exp Res. 1997; 21: 1063-1072
        • Bauer-Moffett C.
        • Altman J.
        The effects of ethanol chronically administered to preweaneing rats on cerebellar development: a morphological study.
        Brain Res. 1977; 119: 249-268
        • Barnes D.E.
        • Walker D.W.
        Prenatal ethanol exposure permanently reduces the number of pyramidal neurons in rat hippocampus.
        Brain Res. 1981; 227: 333-340
        • Kelly S.J.
        Effects of alcohol exposure and artificial rearing during development on septal and hippocampal neurotransmitters in adult rats.
        Alcohol Clin Exp Res. 1996; 20: 670-676
        • Miller M.W.
        Effects of prenatal exposure to ethanol on callosal projection neurons in rat somatosensory cortex.
        Brain Res. 1997; 766: 121-128
        • Miller M.W.
        Effects of alcohol on the generation and migration of cerebral cortical neurons.
        Science. 1986; 233: 1308-1311
        • Miller M.W.
        • Potempa G.
        Numbers of neurons and glia in mature rat somatosensory cortex: effects of prenatal exposure to ethanol.
        J Comp Neurol. 1990; 293: 92-102
        • Takahashi T.
        • Goto T.
        • Miyama S.
        • Nowakowski R.S.
        • Caviness Jr, V.S.
        Sequence of neuron origin and neocortical laminar fate: relation to cell cycle of origin in the developing murine cerebral wall.
        J Neurosci. 1999; 19: 10357-10371
        • Zhu Y.
        • Zhu J.J.
        Rapid arrival and integration of ascending sensory information in layer 1 nonpyramidal neurons and tuft dendrites of layer 5 pyramidal neurons of the neocortex.
        J Neurosci. 2004; 24: 1272-1279
        • O'Malley K.D.
        • Nanson J.
        Clinical implications of a link between fetal alcohol spectrum disorder and attention-deficit hyperactivity disorder.
        Can J Psychiatry. 2002; 47: 349-354
        • Mattson S.N.
        • Roebuck T.M.
        Acquisition and retention of verbal and nonverbal information in children with heavy prenatal alcohol exposure.
        Alcohol Clin Exp Res. 2002; 26: 875-882
        • Coles C.D.
        • Platzman K.A.
        • Lynch M.E.
        • Freides D.
        Auditory and visual sustained attention in adolescents prenatally exposed to alcohol.
        Alcohol Clin Exp Res. 2002; 26: 263-271
        • Bignami A.
        • Dahl D.
        • Rueger D.G.
        Glial fibrillary acidic protein in normal neural cells and pathological conditions.
        Adv Cell Neurobiol. 1980; 1: 285-310
        • Nathaniel E.J.H.
        • Nathaniel D.R.
        The reactive astrocyte.
        Adv Cell Neurobiol. 1981; 2: 249-301
        • Norton W.T.
        • Aquino D.A.
        • Hozumi I.
        • Chiu F.C.
        • Brosnan C.F.
        Quantitative aspects of reactive gliosis: a review.
        Neurochem Res. 1992; 17: 877-885