Although the developing brain is particularly vulnerable to a wide variety of environmental chemicals, little is known about the mechanisms underlying adverse effects following exposure. Normal brain development is orchestrated by precisely timed cellular and molecular events including proliferation, migration, differentiation, synaptogenesis, and programmed cell death (apoptosis). All these processes are potential targets for perturbation by exposures to environmental contaminants during critical developmental periods.

Our laboratory is currently investigating the impact of perinatal exposure to environmental agents on neurogenesis and neuronal differentiation in the developing brain. Both in vivo and in vitro models are being used to identify cellular targets and molecular mechanisms for neurotoxicity. The laboratory uses morphological and biochemical techniques to define toxicant effects on cell proliferation, neuronal migration, neurite development, synaptogenesis and apoptosis. We are also interested in correlating morphologic changes following toxicant exposure with alterations in expression of genes and proteins related to cytoskeletal dynamics, cell cycle control, and neurotrophic factor signaling .

Current projects involve several agents: endocrine disruptors, such as polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); abused substances (toluene and nicotine); and metals (mercury). The long term goal of our research is to determine the relationship between disrupted neuronal production or maturation and functional deficits produced by toxicant exposure during critical periods of brain development.

Selected Publications

Singh KP, Casado FL, Opanashuk LA, Gasiewicz TA. 2008. The aryl hydrocarbon receptor has a normal function in the regulation of hematopoietic and other stem/progenitor cell populations. Biochem Pharmacol. 2008 Oct 15. [Epub ahead of print]

Collins, L. L., Williamson, M.A., Thompson, B.D., Dever, D.P., Gasiewicz, T.A., and Opanashuk, L.A. 2008. 2,3,7,8-Tetracholorodibenzo-p-dioxin exposure disrupts granule neuron precursor maturation in the developing mouse cerebellum. Toxicological Sciences 2008 May;103(1):125-136.

Elder A, Gelein R, Silva V, Feikert T, Opanashuk L, Carter J, Potter R, Maynard A, Ito Y, Finkelstein J, Oberdorster G. 2006. Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environ Health Perspect. Aug;114(8):1172-1178. Erratum in: Environ Health Perspect. 2006 Aug;114(8):1178.

Lee DW, Gelein RM, Opanashuk LA. 2006. Heme-oxygenase-1 promotes polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress and dopaminergic cell injury. Toxicol Sci. Mar;90(1):159-167

Williamson MA, Gasiewicz TA, and Opanashuk LA. 2005. Aryl hydrocarbon receptor expression and activity in cerebellar granule neuroblasts: implications for development and dioxin neurotoxicity. Toxicol Sci. Feb;83(2):340-348.

Barlow BK, Lee DW, Cory-Slechta DA, and Opanashuk LA. 2005. Modulation of antioxidant defense systems by the environmental pesticide maneb in dopaminergic cells. Neurotoxicology. Jan;26(1):63-75.

Lee DW, and Opanashuk LA. 2004. Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in dopaminergic cell injury. Neurotoxicology. Dec;25(6):925-939.

Filbrandt CR, Wu Z, Zlokovic B, Opanashuk L, and Gasiewicz TA. 2004. Presence and functional activity of the aryl hydrocarbon receptor in isolated murine cerebral vascular endothelial cells and astrocytes. Neurotoxicology. 2004 Jun;25(4):605-616.

LoPachin RM, He D, Reid ML, and Opanashuk LA. 2004. 2,5-Hexanedione-induced changes in the monomeric neurofilament protein content of rat spinal cord fractions. Toxicol Appl Pharmacol. Jul 1;198(1):61-73.

Haas KZ, Sperber EF, Opanashuk LA, Stanton PK, and Moshé SL 2001. Resistance of immature hippocampus to morphologic and physiologic alterations following status epilepticus or kindling. Hippocampus 11:615-625.

Opanashuk LA, He DK, Lehning EJ, and LoPachin RM. 2001. Gamma-diketone peripheral neuropathy III. Neurofilament gene expression. Neurotoxicology Apr;22(2):215-220.

Opanashuk, L.A., Pauly, J.R., and Hauser, K.F. 2001. Effect of nicotine on cerebellar granule neuron development.osci. Eur. J. Neurosci. Jan;13(1):48-56.

LoPachin, R.M., Lehning, E.J., Opanashuk, L.A., and Jortner, B.S. 2000. Rate of neurotoxicant exposure determines morphologic manifestations of distal axonopathy. Toxicol. Appl. Pharmacol. Sep 1;167(2):75-86

Chiu, F.C., Opanashuk, L.A., He, D.K., Lehning, E.J., and LoPachin, R.M. 2000. Gamma-diketone peripheral neuropathy. II. Neurofilament subunit content. Toxicol. Appl. Pharmacol. Jun 1;165(2):141-147.