Manganese: Brain transport and emerging research needs

Idiopathic Parkinson's disease (IPD) represents a common neurodegenerative disorder. An estimated 2% of the U.S. population, age 65 and older, develop s IPD. The number of IPD patients will certainly increase over the next sev eral decades as the baby-boomers gradually step into this high-risk age gro up, concomitant with the increase in the average life expectancy. While man y studies have suggested that industrial chemicals and pesticides may under lie [PD, its etiology remains elusive. Among the toxic metals, the relation ship between manganese intoxication and IPD has long been recognized. The n eurological signs of manganism have received close attention because they r esemble several clinical disorders collectively described as extrapyramidal motor system dysfunction, and in particular, IPD and dystonia. However, di stinct dissimilarities between IPD and manganism are well established, and it remains to be determined whether Mn plays an etiologic role in IPD. It i s particularly noteworthy that as a result of a recent court decision, meth ylcyclopentadienyl Mn tricarbonyl (MMT) is presently available in the Unite d States and Canada for use in fuel, replacing lead as an antiknock additiv e. The impact of potential long-term exposure to low levels of MMT combusti on products that may be present in emissions from automobiles has yet to be fully evaluated. Nevertheless, it should be pointed out that recent studie s with Various environmental modeling approaches in the Montreal metropolit an (where MMT has been used for more than 10 years) suggest that airborne M n revels were quite similar to those in areas where MMT was not used. These studies also show that Mn is emitted from the tail pipe of motor vehicles primarily as a mixture of manganese phosphate and manganese sulfate. This b rief review characterizes the Mn speciation in the blood and the transport kinetics of Mn into the central nervous system, a critical step in the accu mulation of Mn within the brain, outlines the potential susceptibility of s elected populations (e.g., iron-deficient) to Mn exposure, and addresses fu ture research needs for Mn.