title: Effects of prenatal chronic mild stress exposure on hippocampal cell proliferation, expression of GSK-3α, β and NR2B in adult offspring during fear extinction in rats.
abstract: Stress during pregnancy has been implicated as a risk factor for the development of many mental disorders; however, the influence of prenatal stress on the fear or anxiety-related behaviors, especially the fear extinction in adult offspring has been little investigated. In order to investigate how prenatal stress affects fear extinction, which is regarded as a form of new learning that counteracts the expression of Pavlovian's conditioned fear, a rat model of prenatal chronic mild stress (PNS) was used to evaluate the effects of PNS on fear extinction in adult offspring. The expression of hippocampal glycogen synthase kinase-3s (GSK-3α, β), N-methyl-d-aspartic acid receptors (NMDARs)-2B and the hippocampal cell proliferation in dentate gyrus in the adult offspring during fear extinction were studied. Our results showed that PNS significantly reduced body weight of pups, indicating PNS might induce growth retardation in offspring. Moreover, PNS significantly enhanced the freezing behavior of offspring at the phase of extinction, suggesting PNS impaired the abilities of fear extinction learning. In addition, PNS significantly increased the levels of GSK-3α, β and NR2B, but reduced hippocampal cell proliferation during fear extinction. Taken together, our findings suggest that maternal stress during pregnancy can impair the fear extinction of adult offspring, probably by affecting the neural plasticity of brain.
authors.affiliation: Department of Psychiatry, the First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Psychiatry, the First Hospital of China Medical University, Shenyang 110001, China. Electronic address: xbli@mail.cmu.edu.cn.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Psychiatry, the First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, the First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Psychiatry, the First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Han
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Psychiatry, the First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, the First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Psychiatry, the First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Cheng
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005108:Extinction, Psychological; D005239:Fear; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha
keywords: Cell proliferation; Fear extinction; GSK-3α; GSK-3β; NR2B; Prenatal chronic mild stress