PMID- 26602365
OWN - NLM
STAT- MEDLINE
DCOM- 20160912
LR  - 20240324
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 12
DP  - 2015 Nov 25
TI  - Late prenatal immune activation causes hippocampal deficits in the absence of 
      persistent inflammation across aging.
PG  - 221
LID - 10.1186/s12974-015-0437-y [doi]
LID - 221
AB  - BACKGROUND: Prenatal exposure to infection and/or inflammation is increasingly 
      recognized to play an important role in neurodevelopmental brain disorders. It 
      has recently been postulated that prenatal immune activation, especially when 
      occurring during late gestational stages, may also induce pathological brain 
      aging via sustained effects on systemic and central inflammation. Here, we tested 
      this hypothesis using an established mouse model of exposure to viral-like immune 
      activation in late pregnancy. METHODS: Pregnant C57BL6/J mice on gestation day 17 
      were treated with the viral mimetic polyriboinosinic-polyribocytidilic acid 
      (poly(I:C)) or control vehicle solution. The resulting offspring were first 
      tested using cognitive and behavioral paradigms known to be sensitive to 
      hippocampal damage, after which they were assigned to quantitative analyses of 
      inflammatory cytokines, microglia density and morphology, astrocyte density, 
      presynaptic markers, and neurotrophin expression in the hippocampus throughout 
      aging (1, 5, and 22 months of age). RESULTS: Maternal poly(I:C) treatment led to 
      a robust increase in inflammatory cytokine levels in late gestation but did not 
      cause persistent systemic or hippocampal inflammation in the offspring. The late 
      prenatal manipulation also failed to cause long-term changes in microglia 
      density, morphology, or activation, and did not induce signs of astrogliosis in 
      pubescent, adult, or aged offspring. Despite the lack of persistent inflammatory 
      or glial anomalies, offspring of poly(I:C)-exposed mothers showed marked and 
      partly age-dependent deficits in hippocampus-regulated cognitive functions as 
      well as impaired hippocampal synaptophysin and brain-derived neurotrophic factor 
      (BDNF) expression. CONCLUSIONS: Late prenatal exposure to viral-like immune 
      activation in mice causes hippocampus-related cognitive and synaptic deficits in 
      the absence of chronic inflammation across aging. These findings do not support 
      the hypothesis that this form of prenatal immune activation may induce 
      pathological brain aging via sustained effects on systemic and central 
      inflammation. We further conclude that poly(I:C)-based prenatal immune activation 
      models are reliable in their effectiveness to induce (hippocampal) neuropathology 
      across aging, but they appear unsuited for studying the role of chronic systemic 
      or central inflammation in brain aging.
FAU - Giovanoli, Sandra
AU  - Giovanoli S
AD  - Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
FAU - Notter, Tina
AU  - Notter T
AD  - Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, 
      Winterthurerstrasse 260, 8057, Zurich, Switzerland.
FAU - Richetto, Juliet
AU  - Richetto J
AD  - Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, 
      Winterthurerstrasse 260, 8057, Zurich, Switzerland.
FAU - Labouesse, Marie A
AU  - Labouesse MA
AD  - Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
FAU - Vuillermot, Stephanie
AU  - Vuillermot S
AD  - Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
FAU - Riva, Marco A
AU  - Riva MA
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano, Milan, Italy.
AD  - Center of Excellence on Neurodegenerative Diseases, Department of Pharmacological 
      and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy.
FAU - Meyer, Urs
AU  - Meyer U
AD  - Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland. 
      urs.meyer@vetpharm.uzh.ch.
AD  - Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, 
      Winterthurerstrasse 260, 8057, Zurich, Switzerland. urs.meyer@vetpharm.uzh.ch.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151125
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Inflammation Mediators)
SB  - IM
MH  - Aging/*immunology/metabolism/*pathology
MH  - Animals
MH  - Female
MH  - Hippocampus/metabolism/*pathology
MH  - Inflammation/immunology/metabolism/pathology
MH  - Inflammation Mediators/*immunology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*immunology/metabolism/*pathology
PMC - PMC4659211
EDAT- 2015/11/26 06:00
MHDA- 2016/09/13 06:00
PMCR- 2015/11/25
CRDT- 2015/11/26 06:00
PHST- 2015/08/28 00:00 [received]
PHST- 2015/11/16 00:00 [accepted]
PHST- 2015/11/26 06:00 [entrez]
PHST- 2015/11/26 06:00 [pubmed]
PHST- 2016/09/13 06:00 [medline]
PHST- 2015/11/25 00:00 [pmc-release]
AID - 10.1186/s12974-015-0437-y [pii]
AID - 437 [pii]
AID - 10.1186/s12974-015-0437-y [doi]
PST - epublish
SO  - J Neuroinflammation. 2015 Nov 25;12:221. doi: 10.1186/s12974-015-0437-y.