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.

Transcranial Focal Electrical Stimulation Modifies Biogenic Amines’ Alterations Induced by 6-Hydroxydopamine in Rat Brain

“…In contrast, we found that 6-OHDA induces enhanced tissue levels of histamine in different brain areas. This effect is similar to the results previously reported by other authors in rats [ 19 , 28 ] and patients with Parkinson’s Disease [ 29 , 30 ]. The high tissue content of histamine may contribute to the neuroinflammation process produced by the toxin administration [ 31 ].…”

The Role of Trace Metals and Environmental Factors in the Onset and Progression of Schizophrenia in Pakistani Population

“…It can also be considered as a neurotransmitter because of its accumulation in presynaptic vesicles during excitation, where it is released and interact with some ionotropic receptors such as AMPA kainate, NMDA and GABA receptors [9]. Similarly abnormal concentrations of manganese in the brain, especially in the basal ganglia, are associated with neurological disorders similar to Parkinson's disease [10]. High levels of Mn in blood can cause the compulsive behavior emotional liability and hallucinations [11].…”

Perinatal Manganese Exposure and Hydroxyl Radical Formation in Rat Brain

“…Several studies report the aftereffects (e.g., reduced intellectual function) of Mn exposure on children at various developmental stages (Woolf et al 2002 ; Wasserman et al 2006 ). Mn crosses the placenta to impair embryonic development (Spencer 1999 ) and produce behavioral abnormalities through childhood and into adulthood (Kwieciński and Nowak 2009 ; Nowak et al 2010 , 2011 ; Brus et al 2012 ; Szkilnik et al 2014 ). It is evident that Mn in excess is toxic to human embryos and fetuses (Colomina et al 1996 ).…”