Manganese neurotoxicity: A focus on the neonate (original) (raw)
Related papers
Biological Trace Element Research, 2006
Neonatal rats were exposed to airborne manganese sulfate (MnSO 4 ) (0, 0.05, 0.5, or 1.0 mg Mn/m 3 ) during gestation (d 0-19) and postnatal days (PNDs) 1-18. On PND 19, rats were killed, and we assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) and tyrosine hydroxylase (TH) protein levels, metallothionein (MT), TH and GS mRNA levels, and reduced and oxidized glutathione (GSH and GSSG, respectively) levels were determined for all five regions. Mn exposure (all three doses) significantly (p = 0.0021) decreased GS protein levels in the cerebellum, and GS mRNA levels were significantly (p = 0.0008) decreased in the striatum. Both the median and high dose of Mn significantly (p = 0.0114) decreased MT mRNA in the striatum. Mn exposure had no effect on TH protein levels, but it significantly lowered TH mRNA levels in the olfactory bulb (p = 0.0402) and in the striatum (p = 0.0493). Mn exposure significantly lowered GSH levels at the median dose in the olfactory bulb (p = 0.0032) and at the median and high dose in the striatum (p = 0.0346). Significantly elevated (p = 0.0247) GSSG, which can be indicative of oxidative stress, was observed in the cerebellum of pups exposed to the high dose of Mn. These data reveal that alterations of oxidative stress biomarkers resulting from in utero and neonatal exposures of airborne Mn exist. Coupled with our previous study in which similarly exposed rats were allowed to recover from Mn exposure for 3 wk, it appears that many of these changes are reversible. It is important to note that the doses of Mn utilized represent levels that are a hundred-to a thousand-fold higher than the inhalation reference concentration set by the United States Environmental Protection Agency.
Effect of Manganese on Neonatal Rat: Manganese Concentration and Enzymatic Alterations in Brain
Acta Pharmacologica et Toxicologica, 2009
Suckling rats were exposed for 15 and 30 days to manganese through the milk of nursing dams receiving 15 mg MnCI,-.IH,O/kg/day orally and after which the neurological manifestations of metal poisoning were studied. N o significant differences in the growth rate, developmental landmarks and walking movements were observed between the control and manganese-exposed pups. The metal concentration was significantly increased in the brain of manganesefed pups at 15 days and exhibited a further threefold increase over the control, at 30 days. The accumulation of the metal in the brain of manganese-exposed nursing dams was comparatively much less. A significant decrease in succinic dehydrogenase, adenosine triphosphatase, adenosine deaminase, acetylcholine esterase and an increase in monoamine oxidase activity was observed in the brain of experimental pups and dams. The results suggest that the developing brain may also be susceptible to manganese.
Manganese exposure and cognitive deficits: A growing concern for manganese neurotoxicity
NeuroToxicology, 2012
This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the ⋆ Xi'an Conference: Summary of Parallel Symposium-12 (ICOH), June 9, 2011. Chair: Harry A. Roels, Université catholique de Louvain, Brussels, Belgium. Co-chair: Rosemarie M. Bowler, San Francisco State University, CA, USA.
Manganese Dosimetry: Species Differences and Implications for Neurotoxicity
Critical Reviews in Toxicology, 2005
Manganese (Mn) is an essential mineral that is found at low levels in food, water, and the air. Under certain high-dose exposure conditions, elevations in tissue manganese levels can occur. Excessive manganese accumulation can result in adverse neurological, reproductive, and respiratory effects in both laboratory animals and humans. In humans, manganese-induced neurotoxicity (manganism) is the overriding concern since affected individuals develop a motor dysfunction syndrome that is recognized as a form of parkinsonism. This review primarily focuses on the essentiality and toxicity of manganese and considers contemporary studies evaluating manganese dosimetry and its transport across the blood-brain barrier, and its distribution within the central nervous system (CNS). These studies have dramatically improved our understanding of the health risks posed by manganese by determining exposure conditions that lead to increased concentrations of this metal within the CNS and other target organs. Most individuals are exposed to manganese by the oral and inhalation routes of exposure; however, parenteral injection and other routes of exposure are important. Interactions between manganese and iron and other divalent elements occur and impact the toxicokinetics of manganese, especially following oral exposure. The oxidation state and solubility of manganese also influence the absorption, distribution, metabolism, and elimination of manganese. Manganese disposition is influenced by the route of exposure. Rodent inhalation studies have shown that manganese deposited within the nose can undergo direct transport to the brain along the olfactory nerve. Species differences in manganese toxicokinetics and response are recognized with nonhuman primates replicating CNS effects observed in humans while rodents do not. Potentially susceptible populations, such as fetuses, neonates, individuals with compromised hepatic function, individuals with suboptimal manganese or iron intake, and those with other medical states (e.g., preparkinsonian state, aging), may have altered manganese metabolism and could be at greater risk for manganese toxicity.
The effects of manganese overexposure on brain health
Neurochemistry International, 2020
Manganese (Mn) is the twelfth most abundant element on the earth and an essential metal to human health. Mn is present at low concentrations in a variety of dietary sources, which provides adequate Mn content to sustain support various physiological processes in the human body. However, with the rise of Mn utility in a variety of industries, there is an increased risk of overexposure to this transition metal, which can have neurotoxic consequences. This risk includes occupational exposure of Mn to workers as well as overall increased Mn pollution affecting the general public. Here, we review exposure due to air pollution and inhalation in industrial settings; we also delve into the toxic effects of manganese on the brain such as oxidative stress, inflammatory response and transporter dysregulation. Additionally, we summarize current understandings underlying the mechanisms of Mn toxicity.