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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Systemic stimulation of TLR2 impairs neonatal mouse brain development
Xiaonan Du1, Bobbi Fleiss, Hongfu Li
1Perinatal Center, Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Plos One
|May 17, 2011
Summary
Neonatal exposure to the Toll-like receptor 2 (TLR2) agonist Pam(3)CSK(4) in mice caused short-term reductions in brain matter and increased organ weight. These effects were not observed in TLR2-deficient mice, indicating TLR2
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Inflammation is a known factor in perinatal brain injury, but mechanisms remain unclear.
- Toll-like receptors (TLRs) mediate inflammatory responses; TLR2's role in the neonatal brain is not well understood.
- This study investigates the impact of TLR2 signaling on neonatal brain development.
Purpose of the Study:
- To examine the effects of a TLR2 agonist on neonatal brain development and function.
- To determine if TLR2 activation influences brain structure, cellularity, and inflammatory markers in early life.
- To assess long-term cognitive consequences of neonatal TLR2 stimulation.
Main Methods:
- Neonatal mice received daily intraperitoneal injections of saline, a TLR2 agonist (Pam(3)CSK(4)), or LPS from postnatal day 3 to 11.
- Brain, spleen, and liver were analyzed at postnatal day 12 and 53 for volume and weight changes.
- Brain sections were assessed for injury markers, neuronal density, microglia activation, and inflammatory cytokines (IL-1β, IL-6, KC, MCP-1).
- Long-term memory was evaluated using the Trace Fear Conditioning test.
Main Results:
- Pam(3)CSK(4) administration led to decreased cerebral gray and white matter volume and increased spleen/liver weight at PND12.
- These effects were absent in TLR2-deficient mice, confirming TLR2 mediation.
- Increased microglia density and elevated IL-1β, IL-6, KC, and MCP-1 were observed in the brain after Pam(3)CSK(4) exposure.
- No significant long-term effects on memory or brain volume were detected at PND53.
Conclusions:
- Repeated systemic exposure to the TLR2 agonist Pam(3)CSK(4) has a transient negative impact on neonatal mouse brain development.
- TLR2 signaling plays a crucial role in mediating inflammatory responses that affect the developing brain.
- Further research is needed to fully elucidate the long-term implications and therapeutic potential related to TLR2 modulation in neonatal brain injury.
