Manganese accumulation in the CNS and associated pathologies

Abstract

Manganese (Mn) is an essential metal for life. It is a key constituent of clue enzymes in the central nervous system, contributing to antioxidant defenses, energetic metabolism, ammonia detoxification, among other important functions. Until now, Mn transport mechanisms are partially understood; however, it is known that it shares some mechanisms of transport with iron. CNS is susceptible to Mn toxicity because it possesses mechanisms that allow Mn entry and favor its accumulation. Cases of occupational Mn exposure have been extensively reported in the literature; however, there are other ways of exposure, such as long-term parental nutrition and liver failure. Manganism and hepatic encephalopathy are the most common pathologies associated with the effects of Mn exposure. Both pathologies are associated with motor and psychiatric disturbances, related in turn to mechanisms of damage such as oxidative stress and neurotransmitters alterations, the dopaminergic system being one of the most affected. Although manganism and Parkinson's disease share some characteristics, they differ in many aspects that are discussed here. The mechanisms for Mn transport and its participation in manganism and hepatic encephalopathy are also considered in this review. It is necessary to find an effective therapeutic strategy to decrease Mn levels in exposed individuals and to treat Mn long term effects. In the case of patients with chronic liver failure it would be worthwhile to test a low-Mn diet in order to ameliorate symptoms of hepatic encephalopathy possibly related to Mn accumulation.

Contribution of metals to brain MR signal intensity: review articles

“…Iron deficiency anemia promotes manganese absorption in the intestine and elevation of the manganese concentration in the blood, but the signal intensity of the globus pallidus on T1WI is not affected [33]. In this way, manganese neurotoxicity is caused by mine dust inhalation or intravenous administration but rarely by oral intake [34,35]. The manganese metabolic pathway adapts to oral MRI contrast agents containing manganese, and the contrast effect of this oral contrast agent based on manganese is limited to liver and intestine [36,37].…”

A Case of Acute Prochloraz-Manganese Complex Intoxication Treated with Extracorporeal Elimination

“…Manganese is a cofactor for a number of important enzymes, including arginase, cholinesterase, phosphoglucomutase, pyruvate carboxylase, mitochondrial superoxide dismutase, and several phosphatases, peptidases and glycosyltransferases [15]. Manganism and hepatic encephalopathy have known as the most common pathologies associated with the effects of manganese exposure [16,17]. Both pathologies are associated with motor and psychiatric disturbances, related in turn to mechanisms of damage such as oxidative stress and neurotransmitters alterations, the dopaminergic system being one of the most affected.…”

Size Fractionation of Metal Species from Serum Samples for Studying Element Biodistribution in Alzheimer’s Disease

“…These alterations have been associated with failures in homeostatic mechanisms responsible for transport and storage of these metals in the organism [38], as well as with an abnormal flux through the blood brain barrier and the choroid plexus [39], provoking their accumulation in brain. Manganese has also been closely related to different neurodegenerative disorders, principally Parkinson's disease, since it can promote multiple neurotoxic mechanisms such as oxidative stress, mitochondrial disruption, or altered metabolism of glutamate and dopamine [40]. However, previous published papers dealing with manganese levels in brain, CSF and blood from AD patients are very confusing.…”