The neurochemical alterations associated with manganese toxicity

Abstract

Manganese (Mn) is an essential metal critical for healthy cellular function; however, exposure to excess environmental Mn can cause systemic and neurological damage. Inhalation of airborne Mn particulate and consumption of Mn-contaminated drinking water are common routes of over-exposure. When Mn-exposure exceeds the capacity of normal Mn removal via the biliary system, ectopic accumulation of this metal can impair the function of several organs, most notably the brain. In the brain, excess Mn is primarily localized within the basal ganglia, where the globus pallidus routinely accumulates the highest concentrations; however, elevated Mn levels also occur in the striatum, substantia nigra, hippocampus, and cortex. Mn accumulation within the basal ganglia impairs neurochemical communication between brain regions, and may result in damage to neurons and glial cells. Mn-induced neurochemical changes have been linked with reduced function of dopamine, glutamate, and γ-amin-obutyric acid (GABA) transport and receptor proteins leading to alterations in signal transduction and promotion of an excitotoxic environment which can manifest as an extrapyramidal disorder similar to Parkinson's disease. This chapter outlines the synaptic changes involved with Mn neurotoxicity, highlighting the influence of excess Mn on dopamine, glutamate, and GABA neurobiology.