Michael Aschner, Ph.D.
Gray E. B. Stahlman Professor of Pediatrics and Pharmacology
Senior Investigator, Kennedy Center for Research on Human Development
Ph.D., University of Rochester, 1985 (Neurobiology and Anatomy)
An important process in the toxic outcome of metal exposure is transport from plasma into the brain across the capillary endothelial cells that comprise the blood-brain barrier. Both essential and non-essential metals are known to play a role in the etiology of developmental brain dysfunction as well as adult onset disease. 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. Studies in the laboratory are currently directed at deciphering the mechanisms of uranium and manganese transport across the barrier. The former has been suggested as a potential factor in Gulf War Syndrome; the latter is known to play a role in Parkinsonism-like syndrome. Major emphasis is directed at the role of the divalent metal transporter-1 protein in the transport of these metals. Additional studies are directed at the mechanisms of methylmercury-induced neurotoxicity, specifically addressing its ability to interfere with Hsp90 chaperone function. Among the client proteins known to bind to Hsp90 are type I (neuronal) nitric oxide synthase and cytosolic prostaglandin E synthase.
Recent Publications
Fitsanakis VA, Piccola G, Marreilha dos Santos AP, Aschner JL, Aschner M. Putative proteins involved in manganese transport across the blood-brain barrier. Hum Exp Toxicol. 2007 26:295-302. Review.
Milatovic D, Yin Z, Gupta RC, Sidoryk M, Albrecht J, Aschner JL, Aschner M. Manganese induces oxidative impairment in cultured rat astrocytes. Toxicol Sci. 2007 98:198-205.
Aschner M, Guilarte TR, Schneider JS, Zheng W. Manganese: recent advances in understanding its transport and neurotoxicity. Toxicol Appl Pharmacol. 2007 221:131-47.
Erikson KM, Dorman DC, Lash LH, Aschner M. Manganese inhalation by rhesus monkeys is associated with brain regional changes in biomarkers of neurotoxicity. Toxicol Sci. 2007 97:459-66.
Aschner M, Syversen T, Souza DO, Rocha JB, Farina M. Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity. Braz J Med Biol Res. 2007 40:285-91.
Zhang Y, Milatovic D, Aschner M, Feustel PJ, Kimelberg HK. Neuroprotection by tamoxifen in focal cerebral ischemia is not mediated by an agonist action at estrogen receptors but is associated with antioxidant activity. Exp Neurol. 2007 204:819-27.
Werdich AA, Baudenbacher F, Dzhura I, Jeyakumar LH, Kannankeril PJ, Fleischer S, LeGrone A, Milatovic D, Aschner M, Strauss AW, Anderson ME, Exil VJ. Polymorphic ventricular tachycardia and abnormal Ca2+ handling in very-long-chain acyl-CoA dehydrogenase null mice. Am J Physiol Heart Circ Physiol. 2007 292:H2202-11.
Aschner M, Dorman DC. Manganese: pharmacokinetics and molecular mechanisms of brain uptake. Toxicol Rev. 2006 25:147-54. Review.
Gupta RC, Milatovic S, Dettbarn WD, Aschner M, Milatovic D. Neuronal oxidative injury and dendritic damage induced by carbofuran: protection by memantine. Toxicol Appl Pharmacol. 2007 219:97-105.
Yin Z, Milatovic D, Aschner JL, Syversen T, Rocha JB, Souza DO, Sidoryk M, Albrecht J, Aschner M. Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes. Brain Res. 2007 1131:1-10.
Kaur P, Aschner M, Syversen T. Role of glutathione in determining the differential sensitivity between the cortical and cerebellar regions towards mercury-induced oxidative stress. Toxicology. 2007 230:164-77.
Erikson KM, Thompson K, Aschner J, Aschner M. Manganese neurotoxicity: a focus on the neonate. Pharmacol Ther. 2007 113:369-77.
Garcia SJ, Gellein K, Syversen T, Aschner M. Iron deficient and manganese supplemented diets alter metals and transporters in the developing rat brain. Toxicol Sci. 2007 95:205-14.
Aschner M, Syversen T, Souza DO, Rocha JB. Metallothioneins: mercury species-specific induction and their potential role in attenuating neurotoxicity. Exp Biol Med (Maywood). 2006 231:1468-73.
Erikson KM, Dorman DC, Fitsanakis V, Lash LH, Aschner M. Alterations of oxidative stress biomarkers due to in utero and neonatal exposures of airborne manganese. Biol Trace Elem Res. 2006 111:199-215.
Fitsanakis VA, Erikson KM, Garcia SJ, Evje L, Syversen T, Aschner M. Brain accumulation of depleted uranium in rats following 3- or 6-month treatment with implanted depleted uranium pellets. Biol Trace Elem Res. 2006 111(1-3):185-97.
Aschner M. Manganese as a potential confounder of serum prolactin. Environ Health Perspect. 2006 114:A458
Walker SJ, Segal J, Aschner M. Cultured lymphocytes from autistic children and non-autistic siblings up-regulate heat shock protein RNA in response to thimerosal challenge. Neurotoxicology. 2006 27:685-92.
Taylor MD, Erikson KM, Dobson AW, Fitsanakis VA, Dorman DC, Aschner M. Effects of inhaled manganese on biomarkers of oxidative stress in the rat brain. Neurotoxicology. 2006 27:788-97.
Aschner M, Fitsanakis VA, dos Santos AP, Olivi L, Bressler JP. Blood-brain barrier and cell-cell interactions: methods for establishing in vitro models of the blood-brain barrier and transport measurements. Methods Mol Biol. 2006 341:1-15. Review.
Gunter TE, Gavin CE, Aschner M, Gunter KK. Speciation of manganese in cells and mitochondria: a search for the proximal cause of manganese neurotoxicity. Neurotoxicology. 2006 27:765-76.
Garcia SJ, Gellein K, Syversen T, Aschner M. A manganese-enhanced diet alters brain metals and transporters in the developing rat. Toxicol Sci. 2006 92:516-25.
Dobson AW, Lack AK, Erikson KM, Aschner M. Depleted uranium is not toxic to rat brain endothelial (RBE4) cells. Biol Trace Elem Res. 2006 110:61-72.
Jiang GC, Aschner M. Neurotoxicity of depleted uranium: reasons for increased concern. Biol Trace Elem Res. 2006110:1-17. Review.
Mutkus L, Aschner JL, Syversen T, Shanker G, Sonnewald U, Aschner M. Mercuric chloride inhibits the in vitro uptake of glutamate in GLAST- and GLT-1-transfected mutant CHO-K1 cells. Biol Trace Elem Res. 2006 109:267-80.
Fitsanakis VA, Zhang N, Avison MJ, Gore JC, Aschner JL, Aschner M. The use of magnetic resonance imaging (MRI) in the study of manganese neurotoxicity. Neurotoxicology. 2006 27:798-806.
Milatovic D, Gupta RC, Aschner M. Anticholinesterase toxicity and oxidative stress. ScientificWorldJournal. 2006 6:295-310. Review.
Fitsanakis VA, Au C, Erikson KM, Aschner M. The effects of manganese on glutamate, dopamine and gamma-aminobutyric acid regulation. Neurochem Int. 2006 48:426-33.
Kaur P, Aschner M, Syversen T. Glutathione modulation influences methyl mercury induced neurotoxicity in primary cell cultures of neurons and astrocytes. Neurotoxicology. 2006 27:492-500.
Aschner M. The transport of manganese across the blood-brain barrier. Neurotoxicology. 2006 27:311-4.
Aschner M, Lukey B, Tremblay A. The Manganese Health Research Program (MHRP): status report and future research needs and directions. Neurotoxicology. 2006 27:733-6.
Gunter KK, Aschner M, Miller LM, Eliseev R, Salter J, Anderson K, Gunter TE. Determining the oxidation states of manganese in NT2 cells and cultured astrocytes. Neurobiol Aging. 2006 27:1816-26.