Early life peripheral lipopolysaccharide challenge reprograms catecholaminergic neurons

Neonatal immune challenge with the bacterial mimetic lipopolysaccharide has the capacity to generate long-term changes in the brain. Neonatal rats were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg) on postnatal day (PND) 3 and again on PND 5. The activation state of tyrosine hydrox...

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Bibliographic Details
Published in:Scientific reports 2017-01, Vol.7 (1), p.40475-40475, Article 40475
Main Authors: Ong, Lin Kooi, Fuller, Erin A, Sominsky, Luba, Hodgson, Deborah M, Dunkley, Peter R, Dickson, Phillip W
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Calcium-Binding Proteins
Catecholamines
Catecholamines - metabolism
Glial Fibrillary Acidic Protein - metabolism
Hydroxylase
Immune system
Lipopolysaccharides
Lipopolysaccharides - pharmacology
Locus coeruleus
Locus Coeruleus - metabolism
Microfilament Proteins
Neonates
Neurons - drug effects
Neurons - metabolism
Phosphorylation
Phosphorylation - drug effects
Rats, Wistar
Rodents
Serine
Substantia nigra
Substantia Nigra - metabolism
Tyrosine 3-monooxygenase
Tyrosine 3-Monooxygenase - metabolism
Ventral Tegmental Area - metabolism
Ventral tegmentum
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Summary:Neonatal immune challenge with the bacterial mimetic lipopolysaccharide has the capacity to generate long-term changes in the brain. Neonatal rats were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg) on postnatal day (PND) 3 and again on PND 5. The activation state of tyrosine hydroxylase (TH) was measured in the locus coeruleus, ventral tegmental area and substantia nigra on PND 85. In the locus coeruleus there was an approximately four-fold increase in TH activity. This was accompanied by a significant increase in TH protein together with increased phosphorylation of all three serine residues in the N-terminal region of TH. In the ventral tegmental area, a significant increase in TH activity and increased phosphorylation of the serine 40 residue was seen. Neonatal lipopolysaccharide had no effect on TH activation in the substantia nigra. These results indicate the capacity of a neonatal immune challenge to generate long-term changes in the activation state of TH, in particular in the locus coeruleus. Overall, the current results demonstrate the enduring outcomes of a neonatal immune challenge on specific brain catecholaminergic regions associated with catecholamine synthesis. This highlights a novel mechanism for long-term physiological and behavioural alterations induced by this model.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep40475