title: Effects of perinatal exposure to lead (Pb) on purine receptor expression in the brain and gliosis in rats tolerant to morphine analgesia.
abstract: The aim of the present study was to investigate the molecular effects of perinatal exposure to lead (Pb) on protein and mRNA expression of purine receptors: P2X4, P2X7, adenosine receptor A1; and astrocytes (GFAP mRNA expression) and on microglia activation (Iba1 mRNA expression) in several structures of the mesolimbic system (striatum, hippocampus, prefrontal cortex) in rats expressing tolerance to the antinociceptive effect of morphine. Rat mothers were orally treated with 0.1% lead acetate from conception, through gestation, and postnatally, as well as to offspring up to day (PND) 28; subsequently molecular studies were conducted on adult (PND 60) male rats. Morphine tolerance developed more strongly in rats perinatally exposed to Pb. The analysis revealed a significant up-regulation of protein and mRNA P2X4 receptor expression in the striatum and prefrontal cortex but not in the hippocampus; P2X7 protein and mRNA receptor expression in the striatum and hippocampus, but not in the prefrontal cortex; A1 protein receptor expression in all investigated structures and A1 mRNA expression in the striatum and hippocampus; Iba1 mRNA expression in the striatum and hippocampus; and GFAP mRNA expression in the striatum and prefrontal cortex. Immunohistochemical analysis has also revealed significant alterations. Strong expressions of P2X4, P2X7, A1 receptors, astrocytes and microglia activation were observed in the hippocampus in Pb and/or morphine treated rats. The higher expression of purine receptors and glial cell activation are important markers of neuroinflammatory processes. Therefore, we conclude that Pb-induced neuroinflammation may be responsible for the intensification of morphine tolerance in the Pb-treated rats. Additionally, the dysregulation of A1 adenosine receptors, mainly in the hippocampus, may also be involved in the intensification of morphine tolerance in Pb-treated rats. Our study demonstrates the significant participation of environmental factors in addictive process; additionally, it shows the necessity of modification of addictive disorder with neuroprotective agents.
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland. Electronic address: irena.bosiacka@ams.edu.pl.
authors.forename: Irena
authors.initials: I
authors.lastname: Baranowska-Bosiacka
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Listos
authors.affiliation: Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Broniewskiego 24, 71-460 Szczecin, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Gutowska
authors.affiliation: Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Machoy-Mokrzyńska
authors.affiliation: Department of Histology and Embryology, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kolasa-Wołosiuk
authors.affiliation: Department of Physiology, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Tarnowski
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Puchałowicz
authors.affiliation: Institute of Occupational Medicine and Environmental Health, Kościelna 13, 41-200 Sosnowiec, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Prokopowicz
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Talarek
authors.affiliation: Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Life Sciences, Głęboka 30, 20-612 Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Listos
authors.affiliation: Department of Neurochemistry, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wąsik
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Chlubek
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004361:Drug Tolerance; D005260:Female; D005911:Gliosis / Q000139:chemically induced* / Q000473:pathology; D007854:Lead / Q000378:metabolism; D007855:Lead Poisoning / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000096:biosynthesis; D011983:Receptors, Purinergic / Q000096:biosynthesis*; D058848:Receptors, Purinergic P2X4 / Q000096:biosynthesis; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D000701:Analgesics, Opioid; D043682:Receptor, Adenosine A1; D011983:Receptors, Purinergic; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D007854:Lead; D009020:Morphine
keywords: A1; Astrocytosis; GFAP; Iba1; Lead (Pb); Morphine tolerance; Neurodegeneration; P2X4; P2X7; Purine receptors expression