title: Early life peripheral lipopolysaccharide challenge reprograms catecholaminergic neurons.
abstract: 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.
authors.affiliation: School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Lin Kooi
authors.initials: LK
authors.lastname: Ong
authors.affiliation: Laboratory of Neuroimmunology, School of Psychology and Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Erin A
authors.initials: EA
authors.lastname: Fuller
authors.affiliation: Laboratory of Neuroimmunology, School of Psychology and Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, Australia.|School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC 3083, Australia.
authors.forename: Luba
authors.initials: L
authors.lastname: Sominsky
authors.affiliation: Laboratory of Neuroimmunology, School of Psychology and Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Hodgson
authors.affiliation: School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Dunkley
authors.affiliation: School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Phillip W
authors.initials: PW
authors.lastname: Dickson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins; D002395:Catecholamines / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000378:metabolism; D008840:Microfilament Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D002395:Catecholamines; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D014446:Tyrosine 3-Monooxygenase