Functional changes in hippocampal synaptic signaling in offspring survivors of a mouse model of intrauterine inflammation

Melissa H. Kelley, Wendy Wu, Jun Lei, Michael McLane, Han Xie, Kyle D. Hart, Leonardo Pereira, Irina Burd, James Maylie

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Recent evidence suggests that exposure to intrauterine inflammation causes acute fetal brain injury and is linked to a spectrum of neurobehavioral disorders. In a rodent model of intrauterine inflammation induced by lipopolysaccharide (LPS) exposure in utero, activated microglia can be detected in the hippocampus of offspring survivors, as late as 60 days postnatal (DPN). Given that the hippocampus is important for learning and memory, these results suggest that in utero inflammation underlies long-term cognitive deficits observed in children/survivors. Methods: An established mouse model of LPS-induced intrauterine inflammation was used to study hippocampal function from offspring at 44-59 DPN. Microgliosis was examined at 45 DPN. Extracellular field recordings of synaptic transmission were performed on acute hippocampal slices. Results: LPS offspring mice displayed persistent microglial activation and increased CA3-CA1 excitatory synaptic strength, which can be explained in part by an increase in the probability of glutamate release, and reduced long-term synaptic potentiation compared to control mice. Conclusions: These results offer a mechanistic explanation for the cognitive and behavioral deficits observed in survivors of preterm birth caused by intrauterine inflammation.

Original languageEnglish (US)
Article number180
JournalJournal of Neuroinflammation
Volume14
Issue number1
DOIs
StatePublished - Sep 5 2017

Fingerprint

Inflammation
Lipopolysaccharides
Hippocampus
Long-Term Potentiation
Premature Birth
Microglia
Synaptic Transmission
Brain Injuries
Glutamic Acid
Rodentia
Learning

Keywords

  • Hippocampus
  • Intrauterine inflammation
  • Long-term synaptic potentiation
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Functional changes in hippocampal synaptic signaling in offspring survivors of a mouse model of intrauterine inflammation. / Kelley, Melissa H.; Wu, Wendy; Lei, Jun; McLane, Michael; Xie, Han; Hart, Kyle D.; Pereira, Leonardo; Burd, Irina; Maylie, James.

In: Journal of Neuroinflammation, Vol. 14, No. 1, 180, 05.09.2017.

Research output: Contribution to journalArticle

Kelley, Melissa H. ; Wu, Wendy ; Lei, Jun ; McLane, Michael ; Xie, Han ; Hart, Kyle D. ; Pereira, Leonardo ; Burd, Irina ; Maylie, James. / Functional changes in hippocampal synaptic signaling in offspring survivors of a mouse model of intrauterine inflammation. In: Journal of Neuroinflammation. 2017 ; Vol. 14, No. 1.
@article{c4e63ab80d9141e7beccb8210380f395,
title = "Functional changes in hippocampal synaptic signaling in offspring survivors of a mouse model of intrauterine inflammation",
abstract = "Background: Recent evidence suggests that exposure to intrauterine inflammation causes acute fetal brain injury and is linked to a spectrum of neurobehavioral disorders. In a rodent model of intrauterine inflammation induced by lipopolysaccharide (LPS) exposure in utero, activated microglia can be detected in the hippocampus of offspring survivors, as late as 60 days postnatal (DPN). Given that the hippocampus is important for learning and memory, these results suggest that in utero inflammation underlies long-term cognitive deficits observed in children/survivors. Methods: An established mouse model of LPS-induced intrauterine inflammation was used to study hippocampal function from offspring at 44-59 DPN. Microgliosis was examined at 45 DPN. Extracellular field recordings of synaptic transmission were performed on acute hippocampal slices. Results: LPS offspring mice displayed persistent microglial activation and increased CA3-CA1 excitatory synaptic strength, which can be explained in part by an increase in the probability of glutamate release, and reduced long-term synaptic potentiation compared to control mice. Conclusions: These results offer a mechanistic explanation for the cognitive and behavioral deficits observed in survivors of preterm birth caused by intrauterine inflammation.",
keywords = "Hippocampus, Intrauterine inflammation, Long-term synaptic potentiation, Synaptic transmission",
author = "Kelley, {Melissa H.} and Wendy Wu and Jun Lei and Michael McLane and Han Xie and Hart, {Kyle D.} and Leonardo Pereira and Irina Burd and James Maylie",
year = "2017",
month = "9",
day = "5",
doi = "10.1186/s12974-017-0951-1",
language = "English (US)",
volume = "14",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Functional changes in hippocampal synaptic signaling in offspring survivors of a mouse model of intrauterine inflammation

AU - Kelley, Melissa H.

AU - Wu, Wendy

AU - Lei, Jun

AU - McLane, Michael

AU - Xie, Han

AU - Hart, Kyle D.

AU - Pereira, Leonardo

AU - Burd, Irina

AU - Maylie, James

PY - 2017/9/5

Y1 - 2017/9/5

N2 - Background: Recent evidence suggests that exposure to intrauterine inflammation causes acute fetal brain injury and is linked to a spectrum of neurobehavioral disorders. In a rodent model of intrauterine inflammation induced by lipopolysaccharide (LPS) exposure in utero, activated microglia can be detected in the hippocampus of offspring survivors, as late as 60 days postnatal (DPN). Given that the hippocampus is important for learning and memory, these results suggest that in utero inflammation underlies long-term cognitive deficits observed in children/survivors. Methods: An established mouse model of LPS-induced intrauterine inflammation was used to study hippocampal function from offspring at 44-59 DPN. Microgliosis was examined at 45 DPN. Extracellular field recordings of synaptic transmission were performed on acute hippocampal slices. Results: LPS offspring mice displayed persistent microglial activation and increased CA3-CA1 excitatory synaptic strength, which can be explained in part by an increase in the probability of glutamate release, and reduced long-term synaptic potentiation compared to control mice. Conclusions: These results offer a mechanistic explanation for the cognitive and behavioral deficits observed in survivors of preterm birth caused by intrauterine inflammation.

AB - Background: Recent evidence suggests that exposure to intrauterine inflammation causes acute fetal brain injury and is linked to a spectrum of neurobehavioral disorders. In a rodent model of intrauterine inflammation induced by lipopolysaccharide (LPS) exposure in utero, activated microglia can be detected in the hippocampus of offspring survivors, as late as 60 days postnatal (DPN). Given that the hippocampus is important for learning and memory, these results suggest that in utero inflammation underlies long-term cognitive deficits observed in children/survivors. Methods: An established mouse model of LPS-induced intrauterine inflammation was used to study hippocampal function from offspring at 44-59 DPN. Microgliosis was examined at 45 DPN. Extracellular field recordings of synaptic transmission were performed on acute hippocampal slices. Results: LPS offspring mice displayed persistent microglial activation and increased CA3-CA1 excitatory synaptic strength, which can be explained in part by an increase in the probability of glutamate release, and reduced long-term synaptic potentiation compared to control mice. Conclusions: These results offer a mechanistic explanation for the cognitive and behavioral deficits observed in survivors of preterm birth caused by intrauterine inflammation.

KW - Hippocampus

KW - Intrauterine inflammation

KW - Long-term synaptic potentiation

KW - Synaptic transmission

UR - http://www.scopus.com/inward/record.url?scp=85028887079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028887079&partnerID=8YFLogxK

U2 - 10.1186/s12974-017-0951-1

DO - 10.1186/s12974-017-0951-1

M3 - Article

C2 - 28874190

AN - SCOPUS:85028887079

VL - 14

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

IS - 1

M1 - 180

ER -