title: Gene-chemical interactions in the developing mammalian nervous system: Effects on proliferation, neurogenesis and differentiation.
abstract: The orderly formation of the nervous system requires a multitude of complex, integrated and simultaneously occurring processes. Neural progenitor cells expand through proliferation, commit to different cell fates, exit the cell cycle, generate different neuronal and glial cell types, and new neurons migrate to specified areas and establish synaptic connections. Gestational and perinatal exposure to environmental toxicants, pharmacological agents and drugs of abuse produce immediate, persistent or late-onset alterations in behavioral, cognitive, sensory and/or motor functions. These alterations reflect the disruption of the underlying processes of CNS formation and development. To determine the neurotoxic mechanisms that underlie these deficits it is necessary to analyze and dissect the complex molecular processes that occur during the proliferation, neurogenesis and differentiation of cells. This symposium will provide a framework for understanding the orchestrated events of neurogenesis, the coordination of proliferation and cell fate specification by selected genes, and the effects of well-known neurotoxicants on neurogenesis in the retina, hippocampus and cerebellum. These three tissues share common developmental profiles, mediate diverse neuronal activities and function, and thus provide important substrates for analysis. This paper summarizes four invited talks that were presented at the 12th International Neurotoxicology Association meeting held in Jerusalem, Israel during the summer of 2009. Donald A. Fox described the structural and functional alterations following low-level gestational lead exposure in children and rodents that produced a supernormal electroretinogram and selective increases in neurogenesis and cell proliferation of late-born retinal neurons (rod photoreceptors and bipolar cells), but not Müller glia cells, in mice. Lisa Opanashuk discussed how dioxin [TCDD] binding to the arylhydrocarbon receptor [AhR], a transcription factor that regulates xenobiotic metabolizing enzymes and growth factors, increased granule cell formation and apoptosis in the developing mouse cerebellum. Alex Zharkovsky described how postnatal early postnatal lead exposure decreased cell proliferation, neurogenesis and gene expression in the dentate gyrus of the adult hippocampus and its resultant behavioral effects. Bernard Weiss illustrated how environmental endocrine disruptors produced age- and sex-dependent alterations in synaptogenesis and cognitive behavior.
authors.affiliation: University of Houston, College of Optometry, Department of Biology and Biochemistry, 4901 Calhoun Road, Houston, TX 77024-2020, USA. dafox@uh.edu
authors.forename: Donald A
authors.initials: DA
authors.lastname: Fox
authors.forename: Lisa
authors.initials: L
authors.lastname: Opanashuk
authors.forename: Aleksander
authors.initials: A
authors.lastname: Zharkovsky
authors.forename: Bernie
authors.initials: B
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009420:Nervous System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats
chemical_list: D009498:Neurotoxins
references.citation: Trends Neurosci. 1998 Sep;21(9):375-82
references.pmid: 9735945
references.citation: Endocrinology. 2008 Mar;149(3):988-94
references.pmid: 18048497
references.citation: Environ Res. 1999 Feb;80(2 Pt 2):S200-S206
references.pmid: 10092434
references.citation: Annu Rev Pharmacol Toxicol. 2000;40:519-61
references.pmid: 10836146
references.citation: Adv Anat Embryol Cell Biol. 1975;50(3):3-88
references.pmid: 1119329
references.citation: Toxicol Appl Pharmacol. 2003 Dec 1;193(2):177-87
references.pmid: 14644620
references.citation: Lancet Neurol. 2004 May;3(5):270
references.pmid: 15099540
references.citation: Biochem Pharmacol. 2003 Aug 15;66(4):527-40
references.pmid: 12906918
references.citation: Biochem Pharmacol. 2000 Jan 1;59(1):65-85
references.pmid: 10605936
references.citation: Chem Biol Interact. 2002 Sep 20;141(1-2):3-24
references.pmid: 12213382
references.citation: J Cell Biol. 1985 Feb;100(2):384-96
references.pmid: 3881455
references.citation: JAMA. 2008 Sep 17;300(11):1303-10
references.pmid: 18799442
references.citation: J Comp Physiol B. 2005 May;175(4):221-30
references.pmid: 15900503
references.citation: Curr Opin Mol Ther. 2006 Aug;8(4):345-51
references.pmid: 16955698
references.citation: J Biol Chem. 1995 Dec 8;270(49):29270-8
references.pmid: 7493958
references.citation: Biochim Biophys Acta. 2003 Feb 17;1619(3):263-8
references.pmid: 12573486
references.citation: Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6731-6
references.pmid: 8692887
references.citation: Annu Rev Pharmacol Toxicol. 1995;35:307-40
references.pmid: 7598497
references.citation: Toxicol Lett. 2007 Aug 30;173(1):41-7
references.pmid: 17669605
references.citation: Ann N Y Acad Sci. 2005 Dec;1055:80-92
references.pmid: 16387720
references.citation: Neurotoxicology. 1997;18(3):645-64
references.pmid: 9339814
references.citation: JAMA. 2002 Nov 6;288(17):2123-9
references.pmid: 12413371
references.citation: Science. 1995 May 5;268(5211):722-6
references.pmid: 7732381
references.citation: Brain Res Brain Res Rev. 1998 Jul;27(2):168-76
references.pmid: 9622620
references.citation: Toxicol Sci. 2005 Feb;83(2):340-8
references.pmid: 15537747
references.citation: J Neurobiol. 2005 Jul;64(1):34-46
references.pmid: 15884004
references.citation: Dev Biol. 2006 Oct 15;298(2):606-15
references.pmid: 16919260
references.citation: Environ Health Perspect. 2008 May;116(5):618-25
references.pmid: 18470321
references.citation: Annu Rev Med. 2005;56:117-37
references.pmid: 15660505
references.citation: Environ Health Perspect. 2007 Jun;115(6):876-82
references.pmid: 17589594
references.citation: Exp Eye Res. 1988 Apr;46(4):613-25
references.pmid: 2838312
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1022-7
references.pmid: 12540825
references.citation: Dev Dyn. 1995 Oct;204(2):144-55
references.pmid: 8589438
references.citation: Neurotoxicol Teratol. 1998 Jan-Feb;20(1):9-17
references.pmid: 9511165
references.citation: Genes Dev. 2006 Oct 15;20(20):2806-19
references.pmid: 17015425
references.citation: Neuron. 1999 Jan;22(1):103-14
references.pmid: 10027293
references.citation: Genes Dev. 1998 Mar 1;12(5):607-20
references.pmid: 9499397
references.citation: Toxicol Appl Pharmacol. 1994 May;126(1):16-25
references.pmid: 8184424
references.citation: Neurotoxicology. 1993 Summer-Fall;14(2-3):191-207
references.pmid: 8247393
references.citation: Toxicol Appl Pharmacol. 1999 Feb 15;155(1):62-70
references.pmid: 10036219
references.citation: Biochem Pharmacol. 2002 Sep;64(5-6):771-80
references.pmid: 12213569
references.citation: Curr Opin Genet Dev. 1999 Oct;9(5):580-7
references.pmid: 10508688
references.citation: Development. 2004 Feb;131(4):819-28
references.pmid: 14757639
references.citation: Early Hum Dev. 1979 Mar;3(1):79-83
references.pmid: 118862
references.citation: J Neurosci Res. 1998 Mar 15;51(6):697-711
references.pmid: 9545084
references.citation: J Toxicol Environ Health B Crit Rev. 2006 Nov-Dec;9(6):485-99
references.pmid: 17090484
references.citation: Environ Health Perspect. 2005 Jun;113(6):675-9
references.pmid: 15929888
references.citation: Curr Opin Cell Biol. 1996 Oct;8(5):679-84
references.pmid: 8939657
references.citation: J Am Geriatr Soc. 2002 Apr;50(4):707-12
references.pmid: 11982672
references.citation: J Neurosci. 1992 Jul;12(7):2549-54
references.pmid: 1613547
references.citation: Annu Rev Pharmacol Toxicol. 1999;39:103-25
references.pmid: 10331078
references.citation: J Comp Neurol. 2005 Jan 17;481(3):252-65
references.pmid: 15593136
references.citation: Brain Res. 1998 Aug 31;804(1):87-94
references.pmid: 9729296
references.citation: Drug Metab Rev. 2006;38(1-2):291-335
references.pmid: 16684662
references.citation: Neuroscience. 2006;138(3):957-65
references.pmid: 16488544
references.citation: Neurotoxicology. 1992 Spring;13(1):27-35
references.pmid: 1508429
references.citation: Pharmacol Biochem Behav. 1996 Dec;55(4):663-71
references.pmid: 8981598
references.citation: J Physiol. 2004 Feb 15;555(Pt 1):153-73
references.pmid: 14578484
references.citation: Neurotoxicol Teratol. 1997 Sep-Oct;19(5):335-46
references.pmid: 9380000
references.citation: Nat Rev Neurosci. 2002 Jan;3(1):24-33
references.pmid: 11823802
references.citation: Exp Eye Res. 1988 Apr;46(4):597-611
references.pmid: 2898378
references.citation: Neurotoxicol Teratol. 2000 Nov-Dec;22(6):811-8
references.pmid: 11120386
references.citation: Invest Ophthalmol Vis Sci. 2002 Jun;43(6):2036-44
references.pmid: 12037016
references.citation: Curr Biol. 1999 Apr 22;9(8):445-8
references.pmid: 10226030
references.citation: Neurotoxicol Teratol. 2000 Jul-Aug;22(4):503-10
references.pmid: 10974588
references.citation: Eur J Neurosci. 2008 Oct;28(8):1618-28
references.pmid: 18973581
references.citation: Dev Dyn. 1995 Oct;204(2):133-43
references.pmid: 8589437
references.citation: J Biol Chem. 2000 Apr 21;275(16):12175-84
references.pmid: 10766853
references.citation: Biochimie. 2001 Jul;83(7):635-43
references.pmid: 11522392
references.citation: Toxicol Sci. 2005 Aug;86(2):365-74
references.pmid: 15788721
references.citation: J Neurosci. 1990 Dec;10(12):4035-9
references.pmid: 2269895
references.citation: Exp Eye Res. 1994 Aug;59(2):203-9
references.pmid: 7835409
references.citation: J Biol Chem. 2003 May 16;278(20):17767-74
references.pmid: 12621046
references.citation: Nat Rev Neurosci. 2001 Jul;2(7):484-91
references.pmid: 11433373
references.citation: N Engl J Med. 2003 Apr 17;348(16):1517-26
references.pmid: 12700371
references.citation: Doc Ophthalmol. 1998-1999;95(3-4):187-215
references.pmid: 10532405
references.citation: Toxicol Sci. 2000 Aug;56(2):382-8
references.pmid: 10910997
references.citation: Dev Dyn. 2000 Jun;218(2):260-79
references.pmid: 10842356
references.citation: Mol Psychiatry. 2000 May;5(3):262-9
references.pmid: 10889528
references.citation: Neuron. 1991 May;6(5):705-15
references.pmid: 2025426
references.citation: Mol Psychiatry. 2002;7(6):609-16
references.pmid: 12140784
references.citation: Food Addit Contam. 2000 Apr;17(4):275-88
references.pmid: 10912242
references.citation: Neuron. 2001 Aug 30;31(4):557-68
references.pmid: 11545715
references.citation: Mol Pharmacol. 2004 Jan;65(1):165-71
references.pmid: 14722248
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2844-9
references.pmid: 9501178
references.citation: Biochem Pharmacol. 2006 Aug 14;72(4):393-404
references.pmid: 16545780
references.citation: J Neurochem. 1999 May;72(5):2099-104
references.pmid: 10217290
references.citation: Trends Neurosci. 2004 Oct;27(10):607-13
references.pmid: 15374672
references.citation: Toxicol Sci. 2008 May;103(1):125-36
references.pmid: 18227101
references.citation: Environ Res. 1999 Oct;81(3):206-14
references.pmid: 10585016
references.citation: Neurotoxicol Teratol. 2001 Sep-Oct;23(5):489-95
references.pmid: 11711252
references.citation: Neurotoxicology. 2007 Sep;28(5):938-50
references.pmid: 17350099
references.citation: Int J Dev Neurosci. 2005 Nov;23(7):627-35
references.pmid: 16150564
references.citation: Environ Res. 1999 Jan;80(1):1-8
references.pmid: 9931221
references.citation: Epidemiology. 2007 Jan;18(1):59-66
references.pmid: 17130688
references.citation: Science. 2000 Feb 11;287(5455):1056-60
references.pmid: 10669420
references.citation: Environ Health Perspect. 2000 Jun;108 Suppl 3:511-33
references.pmid: 10852851
references.citation: Arch Toxicol. 1994;69(2):79-86
references.pmid: 7717865
references.citation: Cereb Cortex. 2003 Sep;13(9):950-61
references.pmid: 12902394
references.citation: Neuroscience. 2007 Mar 30;145(3):1037-47
references.pmid: 17276012
references.citation: Neuron. 2004 Mar 4;41(5):683-6
references.pmid: 15003168
references.citation: J Androl. 2009 May-Jun;30(3):287-97
references.pmid: 19059903
references.citation: J Neurosci. 2003 Mar 1;23(5):1588-92
references.pmid: 12629162
references.citation: Biochem Pharmacol. 2005 May 15;69(10):1403-8
references.pmid: 15857604
references.citation: Chem Biol Interact. 1996 Mar 25;100(2):97-112
references.pmid: 8646792
references.citation: J Comp Neurol. 1990 Nov 15;301(3):433-42
references.pmid: 2262600
references.citation: Brain Res. 1997 Oct 17;771(2):319-28
references.pmid: 9401752
references.citation: J Child Neurol. 1999 Sep;14(9):574-81; discussion 581-2
references.pmid: 10488902
references.citation: Annu Rev Cell Dev Biol. 1996;12:55-89
references.pmid: 8970722
references.citation: Dev Psychopathol. 2005 Summer;17(3):577-97
references.pmid: 16262983
references.citation: Toxicol Sci. 2002 Aug;68(2):479-87
references.pmid: 12151645
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14187-91
references.pmid: 18768812
references.citation: Toxicol Lett. 2001 Mar 31;120(1-3):1-7
references.pmid: 11323156
references.citation: J Toxicol Environ Health A. 2001 Oct 26;64(4):327-42
references.pmid: 11693491
references.citation: Environ Health Perspect. 2008 Mar;116(3):355-61
references.pmid: 18335103