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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
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Early life peripheral lipopolysaccharide challenge reprograms catecholaminergic neurons
Lin Kooi Ong1, Erin A Fuller2, Luba Sominsky2,3
1School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, Australia.
Scientific Reports
|January 11, 2017
Summary
Neonatal exposure to lipopolysaccharide alters brain chemistry long-term. This immune challenge significantly increased tyrosine hydroxylase activity in key brain regions, impacting catecholamine synthesis.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Neonatal immune challenges can induce lasting neurological alterations.
- Lipopolysaccharide (LPS) is a bacterial component that elicits a strong immune response.
- Tyrosine hydroxylase (TH) is a critical enzyme in catecholamine synthesis.
Purpose of the Study:
- To investigate the long-term effects of neonatal lipopolysaccharide (LPS) exposure on tyrosine hydroxylase (TH) activation in specific rat brain regions.
- To determine if neonatal immune challenges induce enduring changes in catecholaminergic pathways.
Main Methods:
- Neonatal rats were injected with LPS on postnatal days 3 and 5.
- Tyrosine hydroxylase (TH) activation, protein levels, and phosphorylation were measured in the locus coeruleus, ventral tegmental area, and substantia nigra on postnatal day 85.
- Enzyme activity assays and Western blotting were utilized.
Main Results:
- Neonatal LPS exposure significantly increased TH activity (approximately four-fold) in the locus coeruleus.
- Increased TH protein and phosphorylation at N-terminal serine residues were observed in the locus coeruleus.
- Significant increases in TH activity and serine 40 phosphorylation were found in the ventral tegmental area.
- No significant changes in TH activation were detected in the substantia nigra.
Conclusions:
- Neonatal immune challenge with LPS causes persistent, region-specific alterations in TH activation in the adult brain.
- The locus coeruleus is particularly sensitive to long-term changes in TH activation following neonatal immune insult.
- These findings suggest a novel mechanism linking early-life immune challenges to enduring neurobiological changes affecting catecholamine synthesis.
