PMID- 26318631
OWN - NLM
STAT- MEDLINE
DCOM- 20160818
LR  - 20181113
IS  - 1873-3360 (Electronic)
IS  - 0306-4530 (Print)
IS  - 0306-4530 (Linking)
VI  - 62
DP  - 2015 Dec
TI  - Prenatal stress programs neuroendocrine stress responses and affective behaviors 
      in second generation rats in a sex-dependent manner.
PG  - 204-16
LID - S0306-4530(15)00883-5 [pii]
LID - 10.1016/j.psyneuen.2015.08.010 [doi]
AB  - An adverse environment in early life is often associated with dysregulation of 
      the hypothalamo-pituitary-adrenal (HPA) axis and higher rates of mood disorders 
      in adulthood. In rats, exposure to social stress during pregnancy results in 
      hyperactive HPA axis responses to stress in the adult offspring and heightened 
      anxiety behavior in the males, but not the females. Here we tested whether, 
      without further intervention, the effects of prenatal stress (PNS) in the first 
      filial generation (F1) are transmitted to the F2 generation via the maternal 
      line. F1 control and PNS female rats were mated with control males and housed 
      under non-stress conditions throughout pregnancy. HPA axis responses to acute 
      stress, anxiety- and depressive-like behavior were assessed in the adult F2 
      offspring. ACTH and corticosterone responses to an acute stressor were markedly 
      enhanced in F2 PNS females compared with controls. This was associated with 
      greater corticotropin releasing hormone (Crh) mRNA expression in the 
      paraventricular nucleus and reduced hippocampal glucocorticoid (Gr) and 
      mineralocorticoid receptor (Mr) mRNA expression. Conversely, in the F2 PNS males, 
      HPA axis responses to acute stress were attenuated and hippocampal Gr mRNA 
      expression was greater compared with controls. F2 PNS males exhibited heightened 
      anxiety-like behavior (light-dark box and elevated plus maze) compared with F2 
      control males. Anxiety-like behavior did not differ between F2 control and PNS 
      females during metestrus/diestrus, however at proestrus/estrus, F2 control 
      females displayed a reduction in anxiety-like behavior, but this effect was not 
      observed in the F2 PNS females. Heightened anxiety in the F2 PNS males was 
      associated with greater Crh mRNA expression in the central nucleus of the 
      amygdala compared with controls. Moreover, Crh receptor-1 (Crhr1) mRNA expression 
      was significantly increased, whereas Crhr2 mRNA was significantly decreased in 
      discrete regions of the amygdala in F2 PNS males compared with controls, with no 
      differences in the F2 females. No differences in depressive-like behavior 
      (sucrose preference or forced swim test) were observed in either sex. In 
      conclusion, the effects of maternal stress during pregnancy on HPA axis 
      regulation and anxiety-like behavior can be transmitted to future generations in 
      a sex-dependent manner. These data have implications for human neuropsychiatric 
      disorders with developmental origins.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Grundwald, Natalia J
AU  - Grundwald NJ
AD  - The Roslin Institute and R (D) SVS, University of Edinburgh, Easter Bush Campus, 
      Midlothian, EH25 9RG, UK.
FAU - Brunton, Paula J
AU  - Brunton PJ
AD  - The Roslin Institute and R (D) SVS, University of Edinburgh, Easter Bush Campus, 
      Midlothian, EH25 9RG, UK. Electronic address: p.j.brunton@ed.ac.uk.
LA  - eng
GR  - BB/F01693X/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/J004332/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150817
PL  - England
TA  - Psychoneuroendocrinology
JT  - Psychoneuroendocrinology
JID - 7612148
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Adrenocorticotropic Hormone/blood
MH  - Animals
MH  - Anxiety/metabolism/physiopathology
MH  - Behavior, Animal/*physiology
MH  - Corticosterone/blood
MH  - Corticotropin-Releasing Hormone/genetics/metabolism
MH  - Depression/metabolism/physiopathology
MH  - Female
MH  - Hippocampus/metabolism
MH  - Hypothalamo-Hypophyseal System/metabolism/*physiopathology
MH  - Male
MH  - Paraventricular Hypothalamic Nucleus/metabolism
MH  - Pituitary-Adrenal System/metabolism/*physiopathology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/metabolism/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glucocorticoid/genetics/metabolism
MH  - Receptors, Mineralocorticoid/genetics/metabolism
MH  - Sex Factors
MH  - Stress, Psychological/metabolism/*physiopathology
PMC - PMC4642655
OTO - NOTNLM
OT  - Anxiety
OT  - Glucocorticoids
OT  - HPA axis
OT  - Prenatal stress
OT  - Sex differences
OT  - Trans-generational
EDAT- 2015/09/01 06:00
MHDA- 2016/08/19 06:00
PMCR- 2015/12/01
CRDT- 2015/08/31 06:00
PHST- 2015/06/18 00:00 [received]
PHST- 2015/08/05 00:00 [revised]
PHST- 2015/08/13 00:00 [accepted]
PHST- 2015/08/31 06:00 [entrez]
PHST- 2015/09/01 06:00 [pubmed]
PHST- 2016/08/19 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - S0306-4530(15)00883-5 [pii]
AID - 10.1016/j.psyneuen.2015.08.010 [doi]
PST - ppublish
SO  - Psychoneuroendocrinology. 2015 Dec;62:204-16. doi: 
      10.1016/j.psyneuen.2015.08.010. Epub 2015 Aug 17.