Professor, Department of Molecular Pharmacology
Professor, Department of Pediatrics
Harold & Muriel Block Chair in Molecular Pharmacology
Director, Einstein Center of Toxicology
Research in our laboratory focuses on the interaction between genetics and the environment in triggering disease both during central nervous system (CNS) development and senescence. We are addressing metal uptake across the blood-brain barrier (BBB) and distribution in the brain (neurons and glia), specifically with methylmercury (MeHg) and manganese (Mn), as well as their cellular and molecular mechanisms of neurotoxicity. Our studies address mechanisms of transport and neurodegeneration in various experimental models (C. elegans, tissue cultures and rodents), as well as follow-up on the sequalae of heavy metal deposition in the brains of human neonates by means of magnetic resonance imaging (MRI).
Hypotheses presently tested include the following: (1) Modulation of C. elegans genes (aat, skn-1, daf-16) that are homologous to mammalian regulators of MeHg uptake and cellular resistance will modify dopaminergic neurodegeneration in response to MeHg exposure. (2) Under conditions of MeHg-induced oxidative stress, Nrf2 (a master regulator of antioxidant responses) coordinates the upregulation of cytoprotective genes that combat MeHg-induced oxidative injury, and that genetic and biochemical changes that negatively impact upon Nrf2 function increase MeHg’s neurotoxicity. (3) PARK2, a strong PD genetic risk factor, alters neuronal vulnerability to modifiers of cellular Mn status, particularly at the level of mitochondrial dysfunction and oxidative stress.
Our studies are ultimately designed to (1) shed novel mechanistic insight into metal-induced neurodegeneration; (2) provide novel targets for genetic or pharmacologic modulation of neurodegenerative disorders; (3) increase knowledge of the pathway involved in oxidative stress, a common etiologic factor in neurodegenerative disorders; (4) develop improved research models for human disease using knowledge of environmental sciences.
Results: (most recent)
Considerations on manganese (Mn) treatments for in vitro studies.
Bowman AB, Aschner M.
Neurotoxicology. 2014 Feb 5. pii: S0161-813X(14)00023-0. doi: 10.1016/j.neuro.2014.01.010. [Epub ahead of print]
Elemental bioimaging of manganese uptake in C. elegans.
Große Brinkhaus S, Bornhorst J, Chakraborty S, Wehe CA, Niehaus R, Reifschneider O, Aschner M, Karst U.
Metallomics. 2014 Jan 30. [Epub ahead of print]
Manganese neurotoxicity: a focus on glutamate transporters.
Karki P, Lee E, Aschner M.
Ann Occup Environ Med. 2013 May 21;25(1):4. doi: 10.1186/2052-4374-25-4.
Manganese in health and disease.
Avila DS, Puntel RL, Aschner M.
Met Ions Life Sci. 2013;13:199-227. doi: 10.1007/978-94-007-7500-8_7.
Yin Yang 1 is a Repressor of Glutamate Transporter EAAT2 and it Mediates Manganese-induced Decrease of EAAT2 Expression in Astrocytes.
Karki P, Webb A, Smith K, Johnson J Jr, Lee K, Son DS, Aschner M, Lee E.
Mol Cell Biol. 2014 Jan 27. [Epub ahead of print]
Effects of diphenyl diselenide on methylmercury toxicity in rats.
Dalla Corte CL, Wagner C, Sudati JH, Comparsi B, Leite GO, Busanello A, Soares FA, Aschner M, Rocha JB.
Biomed Res Int. 2013;2013:983821. doi: 10.1155/2013/983821. Epub 2013 Dec 29.
Sodium-Coupled Neutral Amino Acid Transporter 1 (SNAT1) Modulates L-Citrulline Transport and Nitric Oxide (NO) Signaling in Piglet Pulmonary Arterial Endothelial Cells.
Dikalova A, Fagiana A, Aschner JL, Aschner M, Summar M, Fike CD.
PLoS One. 2014 Jan 15;9(1):e85730. doi: 10.1371/journal.pone.0085730. eCollection 2014 Jan 15.
More Information About Dr. Michael Aschner
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 209
Bronx, NY 10461