title: Effect of pre- and postnatal manganese exposure on brain histamine content in a rodent model of Parkinson's disease.
abstract: Rats lesioned shortly after birth with 6-hydroxydopamine (6-OHDA; 134 μg icv) represent a near-ideal model of severe Parkinson's disease because of the near-total destruction of nigrostriatal dopaminergic fibers. There are scarce data that in Parkinson's disease, activity of the central histaminergic system is increased. The element manganese, an essential cofactor for many enzymatic reactions, itself in toxic amount, replicates some clinical features similar to those of Parkinson's disease. The aim of this study was to examine the effect of neonatal manganese exposure on 6-OHDA modeling of Parkinson's disease in rats, and to determine effects on histamine content in the brain of these rats in adulthood. Manganese (MnCl₂·4H₂O; 10,000 ppm) was included in the drinking water of pregnant Wistar rats from the time of conception until the 21st day after delivery, the age when neonatal rats were weaned. Control rats consumed tap water. Other groups of neonatal rat pups, on the 3rd day after birth, were pretreated with desipramine (20 mg/kg ip 1 h) prior to bilateral icv administration of 6-OHDA (60 or 134 μg) or its vehicle saline-ascorbic (0.1%) (control). At 2 months after birth, in rats lesioned with 60 or 134 μg 6-OHDA, endogenous striatal dopamine (DA) content was reduced, respectively, by 92 and 98% (HPLC/ED), while co-exposure of these groups to perinatal manganese did not magnify the DA depletion. However, there was prominent enhancement of histamine content in frontal cortex, hippocampus, hypothalamus, and medulla oblongata of adult rat brain after 6-OHDA (60 and 134 μg) injection on the day 3rd postnatal day. These findings indicate that histamine and the central histaminergic system are altered in the brain of rats lesioned to model Parkinson's disease, and that manganese enhances effects of 6-OHDA on histamine in brain.
authors.affiliation: Department of Pharmacology, Medical University of Silesia, 41-808 Zabrze, Poland. pharbrus@sum.edu.pl
authors.forename: Ryszard
authors.initials: R
authors.lastname: Brus
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jochem
authors.forename: Przemysław
authors.initials: P
authors.lastname: Nowak
authors.forename: Marta
authors.initials: M
authors.lastname: Adwent
authors.forename: Dariusz
authors.initials: D
authors.lastname: Boroń
authors.forename: Halina
authors.initials: H
authors.lastname: Brus
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kostrzewa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D060766:Drinking Water; D005260:Female; D006632:Histamine / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000633:toxicity*; D018811:Maternal Exposure; D016627:Oxidopamine / Q000008:administration & dosage; D020734:Parkinsonian Disorders / Q000209:etiology / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D060766:Drinking Water; D008345:Manganese; D006632:Histamine; D016627:Oxidopamine; D004298:Dopamine