PMID- 30225350
OWN - NLM
STAT- MEDLINE
DCOM- 20190308
LR  - 20190420
IS  - 2373-2822 (Electronic)
IS  - 2373-2822 (Linking)
VI  - 5
IP  - 4
DP  - 2018 Jul-Aug
TI  - Prospective Analysis of the Effects of Maternal Immune Activation on Rat 
      Cytokines during Pregnancy and Behavior of the Male Offspring Relevant to 
      Schizophrenia.
LID - 10.1523/ENEURO.0249-18.2018 [doi]
LID - ENEURO.0249-18.2018
AB  - Influenza during pregnancy is associated with the development of psychopathology 
      in the offspring. We sought to determine whether maternal cytokines produced 
      following administration of viral mimetic polyinosinic-polycytidylic acid 
      (polyI:C) to pregnant rats were predictive of behavioral abnormalities in the 
      adult offspring. Timed-pregnant Sprague Dawley rats received a single intravenous 
      injection of 4-mg/kg polyI:C or saline on gestational day (GD)15. Blood was 
      collected 3 h later for serum analysis of cytokine levels with ELISA. Male 
      offspring were tested in a battery of behavioral tests during adulthood and 
      behavior was correlated with maternal cytokine levels. Maternal serum levels of 
      CXCL1 and interleukin (IL)-6, but not tumor necrosis factor (TNF)-alpha or CXCL2, 
      were elevated in polyI:C-treated dams. PolyI:C-treated dams experienced 
      post-treatment weight loss and polyI:C pups were smaller than controls at 
      postnatal day (PND)1. Various behavior alterations were seen in the 
      polyI:C-treated offspring. Male polyI:C offspring had enhanced MK-801-induced 
      locomotion, and reduced sociability. PolyI:C offspring failed to display 
      crossmodal and visual memory, and oddity preference was also impaired. 
      Set-shifting, assessed with a lever-based operant conditioning task, was 
      facilitated while touchscreen-based reversal learning was impaired. Correlations 
      were found between maternal serum concentrations of CXCL1, acute maternal 
      temperature and body weight changes, neonatal pup mass, and odd object 
      discrimination and social behavior. Overall, while the offspring of 
      polyI:C-treated rats displayed behavior abnormalities, maternal serum cytokines 
      were not related to the long-term behavior changes in the offspring. Maternal 
      sickness effects and neonatal pup size may be better indicators of later effects 
      of maternal inflammation in the offspring.
FAU - Lins, Brittney R
AU  - Lins BR
AD  - Department of Physiology, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Hurtubise, Jessica L
AU  - Hurtubise JL
AD  - Department of Physiology, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Roebuck, Andrew J
AU  - Roebuck AJ
AD  - Department of Physiology, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Marks, Wendie N
AU  - Marks WN
AD  - Department of Physiology, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Zabder, Nadine K
AU  - Zabder NK
AD  - Department of Physiology, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Scott, Gavin A
AU  - Scott GA
AD  - Department of Physiology, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Greba, Quentin
AU  - Greba Q
AD  - Department of Physiology, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Dawicki, Wojciech
AU  - Dawicki W
AD  - Department of Medicine, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Zhang, Xiaobei
AU  - Zhang X
AD  - Department of Medicine, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Rudulier, Christopher D
AU  - Rudulier CD
AD  - Department of Physiology, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Gordon, John R
AU  - Gordon JR
AD  - Department of Medicine, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
FAU - Howland, John G
AU  - Howland JG
AUID- ORCID: 0000-0003-3326-7118
AD  - Department of Physiology, University of Saskatchewan, Saskatoon S7N 5E5, 
      Saskatchewan, Canada.
LA  - eng
GR  - 125984/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180829
PL  - United States
TA  - eNeuro
JT  - eNeuro
JID - 101647362
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Cxcl1 protein, rat)
RN  - 0 (Cxcl2 protein, rat)
RN  - 0 (Il6 protein, rat)
RN  - 0 (Immunologic Factors)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Behavior, Animal/*physiology
MH  - Chemokine CXCL1/*blood
MH  - Chemokine CXCL2/blood
MH  - Cognitive Dysfunction/etiology/*physiopathology
MH  - Disease Models, Animal
MH  - Female
MH  - Immunologic Factors/pharmacology
MH  - Inflammation/*blood/chemically induced
MH  - Interleukin-6/*blood
MH  - Male
MH  - Poly I-C/pharmacology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Schizophrenia/etiology
MH  - *Social Behavior
MH  - Tumor Necrosis Factor-alpha/blood
PMC - PMC6140112
OTO - NOTNLM
OT  - polyI:C
OT  - recognition memory
OT  - reversal learning
OT  - social behavior
OT  - touchscreen
EDAT- 2018/09/19 06:00
MHDA- 2019/03/09 06:00
PMCR- 2018/08/29
CRDT- 2018/09/19 06:00
PHST- 2018/06/22 00:00 [received]
PHST- 2018/07/31 00:00 [revised]
PHST- 2018/08/06 00:00 [accepted]
PHST- 2018/09/19 06:00 [entrez]
PHST- 2018/09/19 06:00 [pubmed]
PHST- 2019/03/09 06:00 [medline]
PHST- 2018/08/29 00:00 [pmc-release]
AID - eN-NWR-0249-18 [pii]
AID - 10.1523/ENEURO.0249-18.2018 [doi]
PST - epublish
SO  - eNeuro. 2018 Aug 29;5(4):ENEURO.0249-18.2018. doi: 10.1523/ENEURO.0249-18.2018. 
      eCollection 2018 Jul-Aug.