title: Combined effect of maternal serotonin transporter genotype and prenatal stress in modulating offspring social interaction in mice.
abstract: Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum disorders. However, many children exposed to stress prenatally are born healthy and develop typically, suggesting that other factors must contribute to autism. Genes that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in the adult offspring. One candidate gene linked to increased stress reactivity encodes the serotonin transporter. Specifically, an insertion/deletion (long/short allele) polymorphism upstream of the serotonin transporter gene correlates with differential expression and function of the serotonin transporter and a heightened response to stressors. Heterozygous serotonin transporter knockout mice show reductions in serotonin transporter expression similar to the human short polymorphism. In this study, the role of prenatal stress and maternal serotonin transporter genotype were assessed in mice to determine whether their combined effect produces reductions in social behavior in the adult offspring. Pregnant serotonin transporter heterozygous knockout and wild-type dams were placed in either a control condition or subjected to chronic variable stress. The adult offspring were subsequently assessed for social interaction and anxiety using a three-chamber social approach task, ultrasonic vocalization detection, elevated-plus maze and an open field task. Results indicated that prenatal stress and reduced serotonin transporter expression of the dam may have the combined effect of producing changes in social interaction and social interest in the offspring consistent with those observed in autism spectrum disorder. This data indicates a possible combined effect of maternal serotonin transporter genotype and prenatal stress contributing to the production of autistic-like behaviors in offspring.
authors.affiliation: Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Jones
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Smith
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Edwards
authors.forename: Bennet
authors.initials: B
authors.lastname: Givens
authors.forename: Michael R
authors.initials: MR
authors.lastname: Tilley
authors.forename: David Q
authors.initials: DQ
authors.lastname: Beversdorf
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal; D005260:Female; D005838:Genotype; D008425:Maternal Behavior; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012919:Social Behavior
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins
references.citation: Psychopharmacology (Berl). 1987;92(2):180-5
references.pmid: 3110839
references.citation: JAMA. 2009 Jun 17;301(23):2462-71
references.pmid: 19531786
references.citation: Science. 2003 Jul 18;301(5631):386-9
references.pmid: 12869766
references.citation: Neurosci Res. 2004 Dec;50(4):411-7
references.pmid: 15567478
references.citation: Am Fam Physician. 2002 Nov 1;66(9):1667-74
references.pmid: 12449265
references.citation: J Autism Dev Disord. 2008 Mar;38(3):481-8
references.pmid: 17619130
references.citation: Am J Med Genet C Semin Med Genet. 2006 Feb 15;142C(1):40-51
references.pmid: 16419099
references.citation: Am J Psychiatry. 2006 Dec;163(12):2148-56
references.pmid: 17151167
references.citation: Pediatrics. 2009 Nov;124(5):1395-403
references.pmid: 19805460
references.citation: Acta Neuropathol. 2007 May;113(5):559-68
references.pmid: 17235515
references.citation: Psychol Med. 1995 Jan;25(1):63-77
references.pmid: 7792363
references.citation: MMWR Surveill Summ. 2007 Feb 9;56(1):12-28
references.pmid: 17287715
references.citation: Mol Psychiatry. 1997 May;2(3):247-50
references.pmid: 9152989
references.citation: Brain Res. 1999 Jul 17;835(1):18-26
references.pmid: 10448192
references.citation: Science. 1996 Nov 29;274(5292):1527-31
references.pmid: 8929413
references.citation: Neurosci Biobehav Rev. 1997 Jan;21(1):1-10
references.pmid: 8994205
references.citation: J Autism Dev Disord. 2005 Aug;35(4):471-8
references.pmid: 16134032
references.citation: Brain Pathol. 2007 Oct;17(4):434-47
references.pmid: 17919129
references.citation: Early Hum Dev. 2002 Dec;70(1-2):3-14
references.pmid: 12441200
references.citation: Ment Retard Dev Disabil Res Rev. 2004;10(4):248-58
references.pmid: 15666335
references.citation: Neurogenetics. 1999 Apr;2(2):129-31
references.pmid: 10369890
references.citation: Neuropharmacology. 2005 Nov;49(6):798-810
references.pmid: 16183083
references.citation: J Clin Psychiatry. 2005;66 Suppl 10:3-8
references.pmid: 16401144
references.citation: Int J Dev Neurosci. 2005 Apr-May;23(2-3):183-7
references.pmid: 15749244
references.citation: Mol Psychiatry. 2006 Apr;11(4):336-51
references.pmid: 16462816
references.citation: Indian J Pediatr. 2005 Apr;72(4):343-51
references.pmid: 15876765
references.citation: Mol Psychiatry. 2007 Jan;12(1):2-22
references.pmid: 17033636
references.citation: Physiol Behav. 2006 Jul 30;88(4-5):605-14
references.pmid: 16828814
references.citation: Science. 2002 Jul 19;297(5580):400-3
references.pmid: 12130784
references.citation: J Autism Dev Disord. 2001 Dec;31(6):537-43
references.pmid: 11814263
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):329-34
references.pmid: 17182745
references.citation: Alcohol Clin Exp Res. 1997 Nov;21(8):1356-9
references.pmid: 9394104
references.citation: J Neurosci. 2007 Aug 22;27(34):9233-7
references.pmid: 17715358
references.citation: J Child Psychol Psychiatry. 1989 May;30(3):405-16
references.pmid: 2745591
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11545-50
references.pmid: 16055563
references.citation: Mol Psychiatry. 2004 Mar;9(3):264-71
references.pmid: 15094787
references.citation: J Neurochem. 2003 Jul;86(1):210-9
references.pmid: 12807440
references.citation: Pharmacol Biochem Behav. 1988 Dec;31(4):959-62
references.pmid: 3252289
references.citation: Am J Med Genet. 1999 Oct 15;88(5):492-6
references.pmid: 10490705
references.citation: Genes Brain Behav. 2004 Oct;3(5):303-14
references.pmid: 15344923
references.citation: Behav Neurosci. 2003 Feb;117(1):21-31
references.pmid: 12619904
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):79-84
references.pmid: 15635638
references.citation: J Child Psychol Psychiatry. 1977 Sep;18(4):297-321
references.pmid: 562353
references.citation: J Neuropathol Exp Neurol. 2008 Sep;67(9):829-37
references.pmid: 18716561
references.citation: J Neurosci. 2006 Jun 28;26(26):6897-906
references.pmid: 16807320
references.citation: Mol Psychiatry. 2007 Mar;12(3):283-91
references.pmid: 17199132
references.citation: Genes Brain Behav. 2004 Oct;3(5):287-302
references.pmid: 15344922
references.citation: Neurol Clin. 2003 Nov;21(4):915-32, viii
references.pmid: 14743656
references.citation: Mol Pharmacol. 1998 Apr;53(4):649-55
references.pmid: 9547354
references.citation: Nat Rev Genet. 2001 Dec;2(12):943-55
references.pmid: 11733747
references.citation: Behav Genet. 2005 Jan;35(1):31-52
references.pmid: 15674531