Abstract
Neural stem cell (NSC) transplantation has been investigated and developed in areas such as brain injury, stroke and neurodegenerative diseases. Recently, emerging evidence suggest that many of clinical symptoms observed in psychiatric disease are likely related to neural network disruptions including neurogenesis dysfunction. In the present study, we transplanted NSCs into a model of fetal alcohol effects (FAE) for the purpose of investigating the possibility of regenerative therapy for FAE. We labeled NSCs with fluorescent dye and radioisotope which were transplanted into FAE rats by intravenous injection. The transplanted cells were detected in wide areas of brain and were greater in number in the brains of the FAE group compared to the control group. Furthermore NSC transplantation attenuated behavioral abnormalities in FAE animals. These results suggest NSC transplantation as a potential new therapy for human FAE. Keywords
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References
Bearer CF, Swick AR, O’Riordan MA, Cheng G (1999) Ethanol inhibits L1-mediated neurite outgrowth in postnatal rat cerebellar granule cells. J Biol Chem 274: 13264–13270
Bookheimer SY, Sowell ER (2005) Brain imaging in FAS: commentary on the article by Malisza et al. Pediatr Res 58: 1148–1149
Brederlau A, Correia AS, Anisimov SV, Elmi M, Paul G, Roybon L, Morizane A, Bergquist F, Riebe I, Nannmark U, Carta M, Hanse E, Takahashi J, Sasai Y, Funa K, Brundin P, Eriksson PS, Li JY (2006) Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson’s disease: effect of in vitro differentiation on graft survival and teratoma formation. Stem Cells 24: 1433–1440
Brenneman DE, Spong CY, Hauser JM, Abebe D, Pinhasov A, Golian T, Gozes I (2004) Protective peptides that are orally active and mechanistically nonchiral. J Pharmacol Exp Ther 309: 1190–1197
Chaudhuri JD (2000) Alcohol and the developing fetus a review. Med Sci Monit 6: 1031–1041
Chen J, Li Y, Katakowski M, Chen X, Wang L, Lu D, Lu M, Gautam SC, Chopp M (2003) Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res 73: 778–786
Chu K, Kim M, Chae SH, Jeong SW, Kang KS, Jung KH, Kim J, Kim YJ, Kang L, Kim SU, Yoon BW (2004a) Distribution and in situ proliferation patterns of intravenously injected immortalized human neural stemlike cells in rats with focal cerebral ischemia. Neurosci Res 50: 459–465
Chu K, Kim M, Park KI, Jeong SW, Park HK, Jung KH, Lee ST, Kang L, Lee K, Park DK, Kim SU, Roh JK (2004b) Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia. Brain Res 1016: 145–153
Clark CM, Li D, Conry J, Conry R, Loock C (2000) Structural and functional brain integrity of fetal alcohol syndrome in nonretarded cases. Pediatrics 105: 1096–1099
Crews FT, Miller MW, Ma W, Nixon K, Zawada WM, Zakhari S (2003) Neural stem cells and alcohol. Alcohol Clin Exp Res 27: 324–335
Cudd TA (2005) Animal model systems for the study of alcohol teratology. Exp Biol Med 230: 389–393
Endres M, Toso L, Roberson R, Park J, Abebe D, Poggi S, Spong CY (2005) Prevention of alcohol-induced developmental delays and learning abnormalities in a model of fetal alcohol syndrome. Am J Obstet Gynecol 193: 1028–1034
Galindo R, Zamudio PA, Valenzuela CF (2005) Alcohol is a potent stimulant of immature neuronal networks: implications for fetal alcohol spectrum disorder. J Neurochem 94: 1500–1511
Goodlett CR, Horn KH, Zhou FC (2005) Alcohol teratogenesis: mechanisms of damage and strategies for intervention. Exp Biol Med 230: 394–406
Guerri C (1998) Neuroanatomical and neurophysiological mechanisms involved in central nervous system dysfunctions induced by prenatal alcohol exposure. Alcohol Clin Exp Res 22: 304–312
Guerri C, Saez R, Sancho-Tello M, Martin de Aquilera E, Renau-Piqueras J (1990) Ethanol alters astrocyte development: a study of critical periods using primary cultures. Neurochem Res 15: 559–565
Hamre KM, West JR (1993) The effects of the timing of ethanol exposure during the brain growth spurt on the number of cerebellar Purkinje and granule cell nuclear profiles. Alcohol Clin Exp Res 17: 610–622
Haorah J, Heilman D, Knipe B, Chrastil J, Leibhart J, Ghorpade A, Miller DW, Persidsky Y (2005) Ethanol-induced activation of myosin light chain kinase leads to dysfunction of tight junctions and blood-brain barrier compromise. Alcohol Clin Exp Res 229: 999–1009
Ieraci A, Herrera DG (2006) Nicotinamide protects against ethanol-induced apoptotic neurodegeneration in the developing mouse brain. PLoS Med 3: 547–557
Ikonomidou C, Bittigau P, Ishimaru MJ, Wozniak DF, Koch C, Genz K, Price MT, Stefovska V, Horster F, Tenkova T, Dikranian K, Olney JW (2000) Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287: 1056–1060
Jeong SW, Chu K, Jung KH, Kim SU, Kim M, Roh JK (2003) Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke 34: 2258–2263
Kim JA, Gillespie RA, Druse MJ (1997) Effects of maternal ethanol consumption and buspirone treatment on 5-HT1A and 5-HT2A receptors in offspring. Alcohol Clin Exp Res 21: 1169–1178
Lee ST, Chu K, Park JE, Lee K, Kang L, Kim SU, Kim M (2005) Intravenous administration of human neural stem cells induces functional recovery in Huntington’s disease rat model. Neurosci Res 52: 243–249
Lu D, Mahmood A, Wang L, Li Y, Lu M, Chopp M (2001) Adult bone marrow stromal cells administered intravenously to rats after traumatic brain injury migrate into brain and improve neurological outcome. Neuroreport 12: 559–563
McBride JL, Behrstock SP, Chen EY, Jakel RJ, Siegel I, Svendsen CN, Kordower JH (2004) Human neural stem cell transplants improve motor function in a rat model of Huntington’s disease. J Comp Neurol 475: 211–219
Medina AE, Krahe TE, Ramoa AS (2004) Restoration of neuronal plasticity by a phosphodiesterase type 1 inhibitor in a model of fetal alcohol exposure. J Neurosci 26: 1057–1060
Miller MW (1995) Effect of preor postnatal exposure to ethanol on the total number of neurons in the principal sensory nucleus of the trigeminal nerve: cell proliferation and neuronal death. Alcohol Clin Exp Res 19: 1359–1363
Moore DB, Madorsky I, Paiva M, Barrow-Heaton M (2004) Ethanol exposure alters neurotrophin receptor expression in the rat central nervous system: Effects of neonatal exposure. J Neurobiol 60: 114–126
Mueller D, Shamblott MJ, Fox HE, Gearhart JD, Martin LJ (2005) Transplanted human embryonic germ cell-derived neural stem cells replace neurons and oligodendrocytes in the forebrain of neonatal mice with excitotoxic brain damage. J Neurosci Res 82: 592–608
Nash K, Rovet J, Greenbaum R, Fantus E, Nulman I, Koren G (2006) Identifying the behavioural phenotype in Fetal Alcohol Spectrum Disorder: sensitivity, specificity and screening potential. Arch Womens Ment Health 9: 181–186
Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, Galli R, Del Carro U, Amadio S, Bergami A, Furlan R, Comi G, Vescovi AL, Martino G (2003) Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422: 688–694
Ponnappa BC, Rubin E (2000) Modeling alcohol’s effects on organs in animal models. Alcohol Res Health 24: 93–104
Ramanathan R, Wilkemeyer MF, Mittal B, Perides G, Charness ME (1996) Alcohol inhibits cell-cell adhesion mediated by human L1. J Cell Biol 133: 381–390
Rasmussen C (2005) Executive functioning and working memory in fetal alcohol spectrum disorder. Alcohol Clin Exp Res 29: 1359–1367
Riley EP, McGee CL (2005) Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior. Exp Biol Med 230: 357–365
Riley EP, McGee CL, Sowell ER (2004) Teratogenic effects of alcohol: a decade of brain imaging. Am J Med Genet C Semin Med Genet 127: 35–41
Saito T, Tabakoff B, Hoffman PL, Nixon K, Tateno M, Guerri C (2005) The Effects of Ethanol on Neuronal and Glial Differentiation and Development. Alcohol Clin Exp Res 29: 2070–2075
Sakai R, Ukai W, Sohma H, Hashimoto E, Yamamoto M, Ikeda H, Saito T (2005) Attenuation of brain derived neurotrophic factor (BDNF) by ethanol and cytoprotective effect of exogenous BDNF against ethanol damage in neuronal cells. J Neural Transm 112: 1005–1013
Sakata-Haga H, Sawada K, Ohnishi T, Fukui Y (2004) Hydrocephalus following prenatal exposure to ethanol. Acta Neuropathol 108: 393–398
Sari Y, Zhou FC (2004) Prenatal alcohol exposure causes longterm serotonin neuron deficit in mice. Alcohol Clin Exp Res 28: 941–948
Siler-Marsiglio KI, Madorsky I, Pan Q, Paiva M, Neeley AW, Shaw G, Heaton MB (2006) Effects of acute ethanol exposure on regulatory mechanisms of Bcl-2-associated apoptosis promoter, bad, in neonatal rat cerebellum: differential effects during vulnerable and resistant developmental periods. Alcohol Clin Exp Res 30: 1031–1038
Sluyter F, Jamot L, Bertholet JY, Crusio WE (2005) Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse. Behav Brain Funct 22: 5
Sowell ER, Thompson PM, Mattson SN, Tessner KD, Jernigan TL, Riley EP, Toga AW (2002) Regional brain shape abnormalities persist into adolescence after heavy prenatal alcohol exposure. Cereb Cortex 12: 856–865
Spear NE, Molina JC (2005) Fetal or infantile exposure to ethanol promotes ethanol ingestion in adolescence and adulthood: a theoretical review. Alcohol Clin Exp Res 29: 909–929
Spong CY, Abebe DT, Gozes I, Brenneman DE, Hill JM (2001) Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome. J Pharmacol Exp Ther 297: 774–779
Sulik KK (2005) Genesis of alcohol-induced craniofacial dysmorphism. Exp Biol Med 230: 366–375
Sulik KK, Johnston MC, Webb MA (1981) Fetal alcohol syndrome: embryogenesis in a mouse model. Science 214: 936–938
Tan XW, Liao H, Sun L, Okabe M, Xiao ZC, Dawe GS (2005) Fetal microchimerism in the maternal mouse brain: a novel population of fetal progenitor or stem cells able to cross the blood-brain barrier? Stem Cells 23: 1443–1452
Tateno M, Ukai W, Ozawa H, Yamamoto M, Toki S, Ikeda H, Saito T (2004) Ethanol inhibition of neural stem cell differentiation is reduced by neurotrophic factors. Alcohol Clin Exp Res 28: 134S–138S
Tateno M, Ukai W, Yamamoto M, Hashimoto E, Ikeda H, Saito T (2005) The effect of ethanol on cell fate determination of neural stem cells. Alcohol Clin Exp Res 29: 225S–229S
Wang Q, Matsumoto Y, Shindo T, Miyake K, Shindo A, Kawanishi M, Kawai N, Tamiya T, Nagao S (2006) Neural stem cells transplantation in cortex in a mouse model of Alzheimer’s disease. J Med Invest 53: 61–69
Wattendorf DJ, Muenke M (2005) Fetal alcohol spectrum disorders. Am Fam Physician 72: 279–282
Wen Z, Kim HY (2004) Alterations in hippocampal phospholipid profile by prenatal exposure to ethanol. J Neurochem 89: 1368–1377
West JR, Chen WJ, Pantazis NJ (1994) Fetal alcohol syndrome: the vulnerability of the developing brain and possible mechanisms of damage. Metab Brain Dis 9: 291–322
Wilkemeyer MF, Chen SY, Menkari CE, Brenneman DE, Sulik KK, Charness ME (2003) Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity. Proc Natl Acad Sci USA 100: 8543–8548
Zhou FC, Sari Y, Powrozek TA (2005) Fetal alcohol exposure reduces serotonin innervation and compromises development of the forebrain along the serotonergic pathway. Alcohol Clin Exp Res 29: 141–149 141–149
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Yoshinaga, T., Hashimoto, E., Ukai, W., Toki, S., Saito, S., Saito, T. (2007). Neural stem cell transplantation in a model of fetal alcohol effects. In: Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (eds) Neuropsychiatric Disorders An Integrative Approach. Journal of Neural Transmission. Supplementa, vol 72. Springer, Vienna. https://doi.org/10.1007/978-3-211-73574-9_41
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DOI: https://doi.org/10.1007/978-3-211-73574-9_41
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