PMID- 25159716
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1842
IP  - 11
DP  - 2014 Nov
TI  - Long-term effects of combined neonatal and adolescent stress on brain-derived 
      neurotrophic factor and dopamine receptor expression in the rat forebrain.
PG  - 2126-35
LID - S0925-4439(14)00262-2 [pii]
LID - 10.1016/j.bbadis.2014.08.009 [doi]
AB  - Altered brain-derived neurotrophic factor (BDNF) signalling and dopaminergic 
      neurotransmission have been shown in the forebrain in schizophrenia. The 'two 
      hit' hypothesis proposes that two major disruptions during development are 
      involved in the pathophysiology of this illness. We therefore used a 'two hit' 
      rat model of combined neonatal and young-adult stress to assess effects on BDNF 
      signalling and dopamine receptor expression. Wistar rats were exposed to neonatal 
      maternal separation (MS) stress and/or adolescent/young-adult corticosterone 
      (CORT) treatment. At adulthood the medial prefrontal cortex (mPFC), caudate 
      putamen (CPu) and nucleus accumbens (NAc) were analysed by qPCR and Western blot. 
      The 'two hit' combination of MS and CORT treatment caused significant increases 
      in BDNF mRNA and protein levels in the mPFC of male, but not female rats. BDNF 
      mRNA expression was unchanged in the CPu but was significantly reduced by CORT in 
      the NAc. DR3 and DR2 mRNA were significantly up-regulated in the mPFC of two-hit 
      rats and a positive correlation was found between BDNF and DR3 expression in 
      male, but not female rats. DR2 and DR3 expression were significantly increased 
      following CORT treatment in the NAc and a significant negative correlation 
      between BDNF and DR3 and DR2 mRNA levels was found. Our data demonstrate 
      male-specific two-hit effects of developmental stress on BDNF and DR3 expression 
      in the mPFC. Furthermore, following chronic adolescent CORT treatment, the 
      relationship between BDNF and dopamine receptor expression was significantly 
      altered in the NAc. These results elucidate the long-term effects of 'two hit' 
      developmental stress on behaviour.
CI  - Copyright (c) 2014. Published by Elsevier B.V.
FAU - Hill, Rachel A
AU  - Hill RA
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne, Australia.
FAU - Kiss Von Soly, Szerenke
AU  - Kiss Von Soly S
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne, Australia.
FAU - Ratnayake, Udani
AU  - Ratnayake U
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne, Australia.
FAU - Klug, Maren
AU  - Klug M
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne, Australia; Department of Psychology, Swinburne University, Hawthorn, 
      Australia.
FAU - Binder, Michele D
AU  - Binder MD
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne, Australia.
FAU - Hannan, Anthony J
AU  - Hannan AJ
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne, Australia.
FAU - van den Buuse, Maarten
AU  - van den Buuse M
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne, Australia; Department of Pharmacology and Therapeutics, University of 
      Melbourne, Melbourne, Australia; School of Psychological Science, La Trobe 
      University, Melbourne, Australia. Electronic address: 
      m.vandenbuuse@latrobe.edu.au.
LA  - eng
PT  - Journal Article
DEP - 20140823
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
SB  - IM
OTO - NOTNLM
OT  - BDNF
OT  - Dopamine
OT  - Prefrontal cortex
OT  - Sex difference
OT  - Stress
OT  - Striatum
EDAT- 2014/08/28 06:00
MHDA- 2014/08/28 06:01
CRDT- 2014/08/28 06:00
PHST- 2014/06/21 00:00 [received]
PHST- 2014/08/08 00:00 [revised]
PHST- 2014/08/18 00:00 [accepted]
PHST- 2014/08/28 06:00 [entrez]
PHST- 2014/08/28 06:00 [pubmed]
PHST- 2014/08/28 06:01 [medline]
AID - S0925-4439(14)00262-2 [pii]
AID - 10.1016/j.bbadis.2014.08.009 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2014 Nov;1842(11):2126-35. doi: 
      10.1016/j.bbadis.2014.08.009. Epub 2014 Aug 23.