Michael Aschner, Ph.D.
Adjunct Professor, Department of Physiology and Pharmacology
Gray E.B. Stahlman Professor
Pediatrics & Pharmacology
Vanderbilt University
Nashville, Tennessee
e-mail: michael.aschner@vanderbilt.edu
Education
B.S., 1980, University of Rochester, Rochester, NY
M.S., 1983, Anatomy, University of Rochester, Rochester, NY
Ph.D., 1985, Neurobiology and Anatomy, University of Rochester, Rochester, NY
Astrocyte physiology and their role in the modulation of metal and ethanol-induced neurotoxicity
Within the broad area of astrocytic biochemistry and physiology, the laboratory focuses on the role of astrocytes in brain physiology and pathology. Specifically, on-going studies address (1) the mechanisms and consequences of astrocytic swelling, (2) the role of astrocytes in heavy metal (mercury, manganese, and uranium) neurotoxicity, and (3) neurodevelopmental sequelae of environmental exposures to metals and xenobiotics. An important process in the toxic outcome of metals is their transport from plasma into the brain across the capillary endothelial cells that comprise the blood-brain barrier (BBB). In order to cross this barrier, metal complexes must be either highly lipid soluble, or possess affinity for specific carrier-mediated transport systems within the endothelial cell plasma membrane. Little is known about the transport of various metals, and virtually no experimental data exist regarding the transport mechanisms of manganese and uranium across the BBB, a crucial step in their accumulation in the central nervous systems (CNS). Ongoing studies in the lab assess the substrate specificity of manganese and uranium transport into the CNS, testing the hypothesis that the divalent metal cation 1 (DMT-1), which has an unusually broad substrate range that includes Fe2+, Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+ and Pb2+, is mediating their transport into the CNS. Newly incorporated studies encompass magnetic resonance (MR) imaging of metal deposition in the CNS as well as the role of various genes (DMT-1, metallothionein, etc) in modulating neurotoxicity, utilizing mutant c. elegans as a model system. These studies will allow both detailed studies on synaptogenesis and cell migration, providing novel information on neuronal and glial cell development and survival, and pinpointing target specific genes, both in neurodevelopmental and neurodegenerative disorders.
Bibliography (2004)
Costa LG, Aschner M, Vitalone A, Syversen T, Soldin OP. Developmental Neurotoxicity. Ann Rev Pharmacol Toxicol 2004; 44:87-110.
Shanker G, Hampson RE, Aschner M. Methylmercury stimulates arachidonic acid release and cytosolic phospholipase A2 expression in primary neuronal cultures. Neurotoxicology 2004; 25:399-406.
Erikson KM, Dobson AW, Dorman DC, Aschner M. Does manganese induce oxidative stress in the rat brain? Sci Total Environ 2004; 334-335:409-416.
Stredrick DL, Stokes AH, Worst TJ, Freeman WM, Johnson EA, Lash LH, Aschner M, Vrana KE. Manganese-induced cytotoxicity in dopamine-producing cells. Neurotoxicology 2004; 25:543-553
Dobson AW, Erikson KM, Aschner M. Manganese neurotoxicity. Ann New York Acad Sci 2004; 1012:111-114.
Erikson KM, Dorman DC, Lash LH, Dobson, AW, Aschner M. Airborne manganese exposure differentially affects endpoints of oxidative stress in an age and sex-dependent manner. Biol Trace Element Res 2004; 100:49-62.
Erikson KM, Syversen T, Steinnes E, Aschner M. Globus pallidus: a target brain region for divalent metal accumulation associated with dietary iron deficiency. J Nutr Biochem 2004; 15:335-341.
Aschner M, Syversen T. Neurotoxicology: Principles and considerations of in vitro assessment. Alt Lab Animal 2004; 32:323-327.
Aschner M. Book Review, Metal Ions and Neurodegenerative Disorders, edited by Paolo Zatta, World Scientific Publishing Company. Pte. Ltd., 2003. 511 pp. ISBN 981-238-398-0. Biol Trace Element Res 2004.
Updated: 7/05