Preface

Manganese (Mn) is the twelfth most abundant element in the Earth's crust and present in drinking water and in food. As an essential trace element, Mn is required for multiple biochemical and cellular reactions, and is a necessary component for numerous metallo-enzymes, such as Mn superoxide dismutase, arginase, phosphoenol-pyruvate decarboxylase, and glutamine synthase, to name a few.

Despite its essentiality, exposures to high levels of Mn from occupational, iatrogenic, medical, and environmental exposures may contribute to human morbidity. Excessive Mn accumulation in the brain, primarily in basal ganglia, may cause clinical signs and morphological lesions analogous to those seen in Parkinson's disease (PD). Other tissues may be affected as well.

Mn intoxication cases were originally described over two centuries ago. Manganism, resulting from exposure to exceedingly high levels of this metal, was originally described by James Couper (1837), providing insight into the adverse neurological effects in five Scottish men employed in grinding Mn dioxide ore. As Mn began to be used more widely in the steel alloy industry, more cases were recognized, with stronger epidemiological evidence implicating Mn in a number of neurological diseases. Contemporary exposures to Mn at levels described by Couper are rare, yet concerns about the health effects of Mn remain, given its abundant occurrence and the potential exposures throughout various life-stages.

This book, to our knowledge, is the first multidisciplinary scientific endeavor to address the health effects of Mn. It aims to provide state-of-the-art information and deepen the understanding of Mn's adverse health effects. It commences with a description on various pathways for Mn absorption (lung, gastrointestinal tract, olfactory pathway), followed by its nutritional needs, toxicokinetics and toxicodynamics. A large section of the book is devoted to its adverse effects, emphasizing cellular and molecular mechanisms of toxicity in a host of tissues and organs, particularly the nervous system, with emphasis on sensitivity to Mn at various life-stages. We conclude with a list of research needs that will further improve our understanding of the role of Mn both in health and disease.

We called upon internationally recognized experts on Mn to address and facilitate the understanding of its role in health and disease, making a valiant attempt to provide as broad and multidisciplinary approach as possible. Our goal was to assemble a series of chapters that advance the latest developments and scientific breakthroughs in this fast-paced research area, and to provide information that should be of interest to risk assessors, neurobiologists, and neurotoxicologists, as well as metal and trace element biologists. We are hopeful that the book offers the reader appreciation and renewed sense on contemporary issues in Mn research. We are indebted to the authors for their contributions and hope that, as a reader, whether you are a novice or a seasoned Mn researcher, the knowledge amassed herein will stimulate and transform your novel ideas into better understanding on the role of this unique metal in health and disease.

Michael Aschner

Lucio G. Costa