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

• 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

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

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

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