title: Changes in Dpysl2 expression are associated with prenatally stressed rat offspring and susceptibility to schizophrenia in humans.
abstract: Exposure to stress during critical periods of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. In the present study, a repeated-variable stress paradigm was applied to pregnant rats during the last week of gestation, which is analogous to the second trimester of brain development in humans. Behavioral and proteomic analyses were conducted in prenatally-stressed (PNS) adult offspring and non-stressed (NS) adult controls. In the behavioral tests, grooming behavior in the social interaction test, line-crossing behavior in the open field test, and swimming behavior in the forced swimming test were decreased in the PNS group. Western blot analysis and immunohistochemical analysis revealed that the expression of dihydropyrimidinase-like 2 (Dpysl2) or collapsin response mediator protein 2 (Crmp2) was downregulated in the prefrontal cortex and hippocampus of rats in the PNS group. Subsequently, single-nucleotide polymorphisms (SNPs) of the human dihydropyrimidinase-like 2 (DPYSL2) gene were analyzed in a population. Two functional SNPs (rs9886448 in the promoter region and rs2289593 in the exon region) were associated with susceptibility to schizophrenia. The present findings demonstrated that the downregulation of genes such as Dpysl2 and Dypsl3 in a rat model of prenatal stress may affect subsequent behavioral changes and that polymorphisms of the DPYSL2 gene in humans may be associated with the development of schizophrenia. Taken together with previous studies investigating the association between the DPYSL2 gene and schizophrenia, the present findings may contribute additional evidence regarding developmental theories of the pathophysiology of schizophrenia.
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Hwayoung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Jaesoon
authors.initials: J
authors.lastname: Joo
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Nah
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Kyunghee University, Seoul, Republic of Korea.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Hyung-Ki
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Jun-Tack
authors.initials: JT
authors.lastname: Kwon
authors.affiliation: Department of Psychiatry, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Development of Ginseng and Medical Plants Research Institute, Rural Administration, Eumseong, Republic of Korea.
authors.forename: Young Ock
authors.initials: YO
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2
references.citation: Neuropsychopharmacology. 2004 Jul;29(7):1321-30
references.pmid: 15085085
references.citation: Prog Neurobiol. 2010 Mar;90(3):285-326
references.pmid: 19857543
references.citation: Nature. 1995 Aug 10;376(6540):509-14
references.pmid: 7637782
references.citation: J Psychiatry Neurosci. 2005 Sep;30(5):342-8
references.pmid: 16151539
references.citation: Int J Dev Neurosci. 1998 Jun-Jul;16(3-4):209-16
references.pmid: 9785117
references.citation: Eur J Neurosci. 1999 Aug;11(8):2906-16
references.pmid: 10457187
references.citation: Eur J Endocrinol. 2004 Nov;151 Suppl 3:U49-62
references.pmid: 15554887
references.citation: Behav Brain Res. 2005 Jan 30;156(2):251-61
references.pmid: 15582111
references.citation: Neurosci Biobehav Rev. 2005 Apr;29(2):271-81
references.pmid: 15811498
references.citation: Soc Psychiatry Psychiatr Epidemiol. 2005 May;40(5):375-81
references.pmid: 15902407
references.citation: PLoS Med. 2005 Jul;2(7):e212
references.pmid: 16033310
references.citation: Neuron. 2006 Oct 5;52(1):139-53
references.pmid: 17015232
references.citation: Brain Res. 2007 Jul 2;1156:152-67
references.pmid: 17540347
references.citation: J Hum Genet. 2010 Jul;55(7):397-9
references.pmid: 20520616
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2011 Mar;156(2):188-97
references.pmid: 21302347
references.citation: J Biol Chem. 2011 Dec 2;286(48):41466-78
references.pmid: 21953449
references.citation: J Proteomics. 2012 Mar 16;75(6):1764-70
references.pmid: 22230806
references.citation: Dev Neurobiol. 2012 Dec;72(12):1528-40
references.pmid: 22378692
references.citation: J Psychiatr Res. 2013 Jan;47(1):105-12
references.pmid: 23040864
references.citation: Dev Psychobiol. 2013 Mar;55(2):176-92
references.pmid: 22252838
references.citation: Eur Neuropsychopharmacol. 2013 Oct;23(10):1226-46
references.pmid: 23199416
references.citation: Physiol Behav. 1997 Nov;62(5):1087-92
references.pmid: 9333204
references.citation: Acta Psychiatr Scand. 1999 Nov;100(5):344-9
references.pmid: 10563451
references.citation: Am J Psychiatry. 2000 Feb;157(2):190-5
references.pmid: 10671386
references.citation: Curr Opin Neurobiol. 2000 Apr;10(2):205-10
references.pmid: 10753790
references.citation: Mol Psychiatry. 2000 Mar;5(2):142-9
references.pmid: 10822341
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11032-7
references.pmid: 11005874
references.citation: Biol Psychiatry. 2000 Dec 15;48(12):1121-32
references.pmid: 11137052
references.citation: Physiol Behav. 2000 Nov 1-15;71(3-4):353-62
references.pmid: 11150568
references.citation: Neuron. 2000 Nov;28(2):325-34
references.pmid: 11144342
references.citation: Int J Dev Neurosci. 2001 Feb;19(1):37-45
references.pmid: 11226753
references.citation: Science. 2002 Jun 21;296(5576):2225-9
references.pmid: 12029063
references.citation: Biol Psychiatry. 2003 Apr 1;53(7):571-6
references.pmid: 12679234
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2003 Jun;27(4):687-700
references.pmid: 12787858
references.citation: J Neurochem. 2003 Aug;86(3):736-48
references.pmid: 12859686
references.citation: J Neurobiol. 2004 Jan;58(1):34-47
references.pmid: 14598368
references.citation: Neurosci Biobehav Rev. 2008 Aug;32(6):1073-86
references.pmid: 18423592
references.citation: Paediatr Perinat Epidemiol. 2008 Sep;22(5):438-66
references.pmid: 18782252
references.citation: Ann Acad Med Singapore. 2009 May;38(5):402-6
references.pmid: 19521639
references.citation: Synapse. 2009 Sep;63(9):794-804
references.pmid: 19489049
references.citation: J Biol Chem. 2009 Nov 6;284(45):31375-90
references.pmid: 19755421
references.citation: Arch Gen Psychiatry. 1978 Apr;35(4):429-31
references.pmid: 727894