title: The effect of low levels of lead (Pb) in the blood on levels of sphingosine-1-phosphate (S1P) and expression of S1P receptor 1 in the brain of the rat in the perinatal period.
abstract: Sphingolipids are the main components of the lipid membrane. They also perform structural functions and participate in many signal transmission processes. One of the bioactive sphingolipids is sphingosine-1-phosphate (S1P), a ligand for five G protein-coupled receptors (S1PRs1-5), which can also act as an intracellular second messenger. S1P is responsible for the stimulation of progenitor cells in the brain, but it can also induce apoptosis of mature neurons. This study is aimed at assessing the effect of pre- and neonatal exposure to permissible Pb concentrations on S1P levels and S1PR1 (EDG1) expression in the prefrontal cortex, cerebellum, and hippocampus of rats. The concentrations of S1P were determined by RP-HPLC, S1PR1 expression was determined by RT PCR and Western Blot, and receptor immunolocalization was determined by immunohistochemistry method. Our results showed that even low blood Pb concentrations, i.e. within the acceptable limit of 10 μg/dL caused changes in the concentration of S1P in the cerebellum, prefrontal cortex, and hippocampus. Our data also showed a significant decrease in the level of S1PR1 in all studied part of brain, without significant changes in S1PR1 gene expression. Pre- and neonatal exposure to Pb also resulted in a decrease in the expression of S1PR1 in glial cells in all regions of the Cornu Ammonis (CA1-CA4) and Dentate Gyrus in the hippocampus, as well as in all layers of the cerebellum and prefrontal cortex, compared to the unexposed control group.
authors.affiliation: Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Broniewskiego 24, 71-460 Szczecin, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Łukomska
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland. Electronic address: ika@pum.edu.pl.
authors.forename: I
authors.initials: I
authors.lastname: Baranowska-Bosiacka
authors.affiliation: Department of Microbiology and Immunology, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Budkowska
authors.affiliation: Department of Histology and Embryology, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Pilutin
authors.affiliation: Department of Physiology, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Tarnowski
authors.affiliation: Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Broniewskiego 24, 71-460 Szczecin, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Dec
authors.affiliation: Department of Histology and Embryology, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Dołęgowska
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Metryka
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Chlubek
authors.affiliation: Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Broniewskiego 24, 71-460 Szczecin, Poland.
authors.forename: I
authors.initials: I
authors.lastname: Gutowska
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007854:Lead / Q000097:blood*; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D011897:Random Allocation; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D014018:Tissue Distribution
chemical_list: D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C578616:S1PR1 protein, rat; D000081025:Sphingosine-1-Phosphate Receptors; C060506:sphingosine 1-phosphate; D007854:Lead; D013110:Sphingosine
keywords: Brain; Lead (Pb); Neonatal Pb exposure; Prenatal Pb exposure; S1P receptor 1 expression; Sphingosine-1-phosphate (S1P)