PMID- 29539630
OWN - NLM
STAT- MEDLINE
DCOM- 20181109
LR  - 20181109
IS  - 1421-9859 (Electronic)
IS  - 0378-5866 (Linking)
VI  - 40
IP  - 2
DP  - 2018
TI  - Altered Hippocampal Gene Expression and Morphology in Fetal Piglets following 
      Maternal Respiratory Viral Infection.
PG  - 104-119
LID - 10.1159/000486850 [doi]
AB  - Maternal infection during pregnancy increases the risk of neurobehavioral 
      problems in offspring. Evidence from rodent models indicates that the maternal 
      immune response to infection can alter fetal brain development, particularly in 
      the hippocampus. However, information on the effects of maternal viral infection 
      on fetal brain development in gyrencephalic species is limited. Thus, the 
      objective of this study was to assess several effects of maternal viral infection 
      in the last one-third of gestation on hippocampal gene expression and development 
      in fetal piglets. Pregnant gilts were inoculated with porcine reproductive and 
      respiratory syndrome virus (PRRSV) at gestational day (GD) 76 and the fetuses 
      were removed by cesarean section at GD 111 (3 days before anticipated 
      parturition). The gilts infected with PRRSV had elevated plasma interleukin-6 
      levels and developed transient febrile and anorectic responses lasting 
      approximately 21 days. Despite having a similar overall body weight, fetuses from 
      the PRRSV-infected gilts had a decreased brain weight and altered hippocampal 
      gene expression compared to fetuses from control gilts. Notably, maternal 
      infection caused a reduction in estimated neuronal numbers in the fetal dentate 
      gyrus and subiculum. The number of proliferative Ki-67+ cells was not altered, 
      but the relative integrated density of GFAP+ staining was increased, in addition 
      to an increase in GFAP gene expression, indicating astrocyte-specific gliosis. 
      Maternal viral infection caused an increase in fetal hippocampal gene expression 
      of the inflammatory cytokines TNF-alpha and IFN-gamma and the myelination marker myelin 
      basic protein. MHCII protein, a classic monocyte activation marker, was reduced 
      in microglia, while expression of the MHCII gene was decreased in hippocampal 
      tissue of the fetuses from PRRSV-infected gilts. Together, these data suggest 
      that maternal viral infection at the beginning of the last trimester results in a 
      reduction in fetal hippocampal neurons that is evident 5 weeks after infection, 
      when fetal piglets are near full term. The neuronal reduction was not accompanied 
      by pronounced neuroinflammation at GD 111, indicating that any activation of 
      classic neuroinflammatory pathways by maternal viral infection, if present, is 
      mostly resolved by parturition.
CI  - (c) 2018 S. Karger AG, Basel.
FAU - Antonson, Adrienne M
AU  - Antonson AM
AD  - Department of Animal Sciences, Laboratory of Integrative Immunology and Behavior, 
      University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
FAU - Balakrishnan, Bindu
AU  - Balakrishnan B
AD  - Department of Animal Sciences, Laboratory of Integrative Immunology and Behavior, 
      University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
FAU - Radlowski, Emily C
AU  - Radlowski EC
AD  - Department of Animal Sciences, Laboratory of Integrative Immunology and Behavior, 
      University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
FAU - Petr, Geraldine
AU  - Petr G
AD  - Department of Animal Sciences, Laboratory of Integrative Immunology and Behavior, 
      University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
FAU - Johnson, Rodney W
AU  - Johnson RW
AD  - Department of Animal Sciences, Laboratory of Integrative Immunology and Behavior, 
      University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
AD  - Division of Nutritional Sciences, University of Illinois Urbana-Champaign, 
      Urbana, Illinois, USA.
AD  - Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, Illinois, 
      USA.
LA  - eng
GR  - R01 HD069899/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180314
PL  - Switzerland
TA  - Dev Neurosci
JT  - Developmental neuroscience
JID - 7809375
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Female
MH  - Fetal Development
MH  - Fetus
MH  - Gene Expression
MH  - Hippocampus/*pathology
MH  - *Porcine Reproductive and Respiratory Syndrome
MH  - Porcine respiratory and reproductive syndrome virus
MH  - Pregnancy
MH  - *Pregnancy Complications, Infectious
MH  - *Prenatal Exposure Delayed Effects/genetics/pathology
MH  - Swine
OTO - NOTNLM
OT  - Fetal pig
OT  - Hippocampus
OT  - Maternal immune activation
OT  - Microglia
OT  - Neurogenesis
OT  - Neuroinflammation
OT  - Prenatal insult
EDAT- 2018/03/15 06:00
MHDA- 2018/11/10 06:00
CRDT- 2018/03/15 06:00
PHST- 2017/06/27 00:00 [received]
PHST- 2018/01/15 00:00 [accepted]
PHST- 2018/03/15 06:00 [pubmed]
PHST- 2018/11/10 06:00 [medline]
PHST- 2018/03/15 06:00 [entrez]
AID - 000486850 [pii]
AID - 10.1159/000486850 [doi]
PST - ppublish
SO  - Dev Neurosci. 2018;40(2):104-119. doi: 10.1159/000486850. Epub 2018 Mar 14.