Manganese neurotoxicity: behavioral disorders associated with dysfunctions in the basal ganglia and neurochemical transmission

摘要

Manganese (Mn) is an essential element required for many physiological functions. While it is essential at physiological levels, excessive accumulation of Mn in the brain causes severe dysfunctions in the central nervous system known as manganism. Manganism is an extrapyramidal disorder characterized by motor disturbances associated with neuropsychiatric and cognitive disabilities similar to Parkinsonism. As the primary brain regions targeted by Mn are the basal ganglia, known to be involved in the pathophysiology of extrapyramidal disorders, this review will examine the impact of Mn exposure on the basal ganglia circuitry and neurotransmitters in relation to motor and non-motor disorders. The collected data from recent available studies in humans and experimental animal models provide new information about the mechanisms by which Mn affects behavior, neurotransmitters, and basal ganglia function observed in manganism. The effects of the alterations of metals on basal ganglia and neurochemical functioning are critical to develop effective modalities not only for the treatment of vulnerable populations (e.g., Mn-exposed workers) but also for understanding the etiology of neurodegenerative diseases where brain metal imbalances are involved, such as Parkinson's disease.