title: Sustained Effects of Neonatal Systemic Lipopolysaccharide on IL-1β and Nrf2 in Adult Rat Substantia Nigra Are Partly Normalized by a Spirulina-Enriched Diet.
abstract: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin (IL)-1β, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxisome proliferator-activated receptor γ coactivator (PGC)-1α in rat SN.
  
  
  
  Five-day-old rat pups were treated with LPS (i.p. 2 mg/kg). After 65 days, the mRNA level of IL-1β was significantly increased, in parallel with a decrease in that of the rate-limiting enzyme in glutathione synthesis, the γ-glutamylcysteine ligase catalytic subunit (γGCLc), Nrf2, and brain-derived neurotrophic factor (BDNF). Protein levels of γGCLc and Nrf2 were decreased while IL-1β protein was significantly increased. These LPS-induced long-term changes correlated with a decrease in phosphorylated (active) AKT (pAKT) and phosphorylated (inactive) GSK-3β (pGSK-3β). In another set of experiments, a 0.1% Spirulina-containing diet was given to lactating mothers 24 h before the LPS treatment of the pups. The Spirulina-supplemented diet decreased IL-1β protein expression in SN and elevated the mRNA level of γGCLc, Nrf2 protein, PGC-1α protein, and pAKT.
  
  
  
  Early-life infection can negatively affect Nrf2, pAKT, and pGSK-3β for a long time in SN. A diet enriched with antioxidant and anti-inflammatory phytochemicals can partly restore some, but not all, of the effects on the antioxidant defense, possibly via normalizing effects on pAKT.
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jaspal
authors.initials: J
authors.lastname: Patil
authors.forename: Ashok
authors.initials: A
authors.lastname: Matte
authors.forename: Hans
authors.initials: H
authors.lastname: Nissbrandt
authors.forename: Carina
authors.initials: C
authors.lastname: Mallard
authors.forename: Mats
authors.initials: M
authors.lastname: Sandberg
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004044:Dietary Proteins / Q000008:administration & dosage*; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053545:Spirulina; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D004044:Dietary Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat