title: Prenatal chronic mild stress induces depression-like behavior and sex-specific changes in regional glutamate receptor expression patterns in adult rats.
abstract: Chronic stress during critical periods of human fetal brain development is associated with cognitive, behavioral, and mood disorders in later life. Altered glutamate receptor (GluR) expression has been implicated in the pathogenesis of stress-dependent disorders. To test whether prenatal chronic mild stress (PCMS) enhances offspring's vulnerability to stress-induced behavioral and neurobiological abnormalities and if this enhanced vulnerability is sex-dependent, we measured depression-like behavior in the forced swimming test (FST) and regional changes in GluR subunit expression in PCMS-exposed adult male and female rats. Both male and female PCMS-exposed rats exhibited stronger depression-like behavior than controls. Males and females exhibited unique regional changes in GluR expression in response to PCMS alone, FST alone (CON-FST), and PCMS with FST (PCMS-FST). In females, PCMS alone did not alter N-methyl-d-aspartate receptor (NMDAR) or metabotropic glutamate receptor (mGluR) expression, while in PCMS males, higher mGluR2/3, mGluR5, and NR1 expression levels were observed in the prefrontal cortex. In addition, PCMS altered the change in GluR expression induced by acute stress (the FST test), and this too was sex-specific. Male PCMS-FST rats expressed significantly lower mGluR5 levels in the hippocampus, lower mGluR5, NR1, postsynaptic density protein (PSD)95, and higher mGluR2/3 in the prefrontal cortex, and higher mGluR5 and PSD95 in the amygdala than male CON-FST rats. Female PCMS-FST rats expressed lower NR1 in the hippocampus, lower NR2B and PSD95 in the prefrontal cortex, lower mGluR2/3 in the amygdala, and higher PSD95 in the amygdala than female CON-FST rats. PCMS may increase the offspring's vulnerability to depression by altering sex-specific stress-induced changes in glutamatergic signaling.
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Humanities and Social Sciences, Applied Psychology, China Medical University, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Essential Qualities Oriented Education College, Liaoning Finance Vocational College, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.affiliation: College of Humanities and Social Sciences, Applied Psychology, China Medical University, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.affiliation: The Research Center for Medical Genomics, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Psychological Counseling Room, Hebei Institute of Foreign Language, PR China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Center for Mental Health Control and Prevention, The Third People's Hospital of Liaoning, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, PR China. Electronic address: xbli@mail.cmu.edu.cn.
authors.forename: X
authors.initials: X
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism; D003863:Depression / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D046353:Immobility Response, Tonic; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000150:complications*; D013550:Swimming / Q000523:psychology
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017470:Receptors, Glutamate
keywords: depression; glutamate receptors; prenatal stress; sex difference