Changes in Dpysl2 expression are associated with prenatally stressed rat offspring and susceptibility to schizophrenia in humans
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, singlenucleotide 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
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Document Type: Research Article
Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea
Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea
Department of Neuropsychiatry, School of Medicine, Kyunghee University, Seoul, Republic of Korea
Department of Psychiatry, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea
Development of Ginseng and Medical Plants Research Institute, Rural Administration, Eumseong, Republic of Korea
January 1, 2015
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