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Sustained Effects of Neonatal Systemic Lipopolysaccharide on IL-1 beta and Nrf2 in Adult Rat Substantia Nigra Are Partly Normalized by a Spirulina-Enriched Diet

Journal article
Authors Jaspal Patil
Ashok Matte
Hans Nissbrandt
Carina Mallard
Mats Sandberg
Published in Neuroimmunomodulation
Volume 23
Issue 4
Pages 250-259
ISSN 1021-7401
Publication year 2016
Published at Institute of Neuroscience and Physiology, Department of Physiology
Institute of Neuroscience and Physiology, Department of Pharmacology
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 250-259
Language en
Links dx.doi.org/10.1159/000452714
Keywords Neuroinflammation, Nrf2, Antioxidant system, Spirulina, NRF2-INDUCIBLE ANTIOXIDANT DEFENSE, NRF2-ENCODING NFE2L2 HAPLOTYPES, MESSENGER-RNA EXPRESSION, PARKINSONS-DISEASE, MITOCHONDRIAL BIOGENESIS, ALPHA-SYNUCLEIN, P38 MAPK, BDNF, BRAIN, NEUROPROTECTION
Subject categories Neurosciences

Abstract

Background/Aim: 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)-1 beta, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxi-some proliferator-activated receptor gamma coactivator (PGC)-1 alpha in rat SN. Method and Results: Five-day-old rat pups were treated with LPS (i. p. 2 mg/kg). After 65 days, the mRNA level of IL-1 beta was significantly increased, in parallel with a decrease in that of the rate-limiting enzyme in glutathione synthesis, the gamma-glutamylcysteine ligase catalytic subunit (gamma GCLc), Nrf2, and brain-derived neurotrophic factor (BDNF). Protein levels of gamma GCLc and Nrf2 were decreased while IL-1 beta protein was significantly increased. These LPS-induced long-term changes correlated with a decrease in phosphorylated (active) AKT (pAKT) and phosphorylated (inactive) GSK-3 beta (pGSK-3 beta). 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-1 beta protein expression in SN and elevated the mRNA level of gamma GCLc, Nrf2 protein, PGC-1 alpha protein, and pAKT. Conclusion: Early-life infection can negatively affect Nrf2, pAKT, and pGSK-3 beta for a long time in SN. A diet en-riched 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. (C) 2016 S. Karger AG, Basel

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