Numerous receptor systems in various brain regions have been reported to be affected by toxicant exposure. This project will examine the role of toxicant-induced changes in receptors to functional changes in the cell such as the ability to maintain calcium homeostasis. This process plays a critical regulatory role in cell-cell communication and signaling. A disruption in intracellular calcium can disrupt the calcium-mediated signal transduction processes resulting in a cascade of intracellular effects. Intracellular calcium has been examined in subcellular components of the nervous system following exposure to environmental agents such as inorganic lead and polychlorinated biphenyls. Using a primary cell culture system of cerebellar granule cells, this project has examined the effects of PCBs on cellular calcium homeostasis in both a population of cells as well as individual cellular responses. Initial studies have examined the developmental ontogeny of the second messenger system in the visual system. Alterations in this profile will be studied as a measure of visual sensory functioning in the developing animal following exposure to an environmental agent. Immunohistological studies are underway to examine alterations in neuronal distribution of a calcium binding protein, Calbindin 28K, and its potential role in determining the cellular pattern of perturbation in the nervous system either following exposure to an environmental agent or during the aging process.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
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Harry, G Jean; McPherson, Christopher A; Wine, Robert N et al. (2004) Trimethyltin-induced neurogenesis in the murine hippocampus. Neurotox Res 5:623-7
McPherson, Christopher A; Kubik, Julie; Wine, Robert N et al. (2003) Alterations in cyclin A, B, and D1 in mouse dentate gyrus following TMT-induced hippocampal damage. Neurotox Res 5:339-54
Harry, G Jean; Lefebvre d'Hellencourt, Christian (2003) Dentate gyrus: alterations that occur with hippocampal injury. Neurotoxicology 24:343-56
Harry, G Jean; Tyler, Kelly; d'Hellencourt, Christian Lefebvre et al. (2002) Morphological alterations and elevations in tumor necrosis factor-alpha, interleukin (IL)-1alpha, and IL-6 in mixed glia cultures following exposure to trimethyltin: modulation by proinflammatory cytokine recombinant proteins and neutralizing antibodies. Toxicol Appl Pharmacol 180:205-18
Jahnke, G D; Brunssen, S; Maier, W E et al. (2001) Neurotoxicant-induced elevation of adrenomedullin expression in hippocampus and glia cultures. J Neurosci Res 66:464-74
Harry, G J; Lefebvre d'Hellencourt, C; Bruccoleri, A et al. (2000) Age-dependent cytokine responses: trimethyltin hippocampal injury in wild-type, APOE knockout, and APOE4 mice. Brain Behav Immun 14:288-304
Bruccoleri, A; Harry, G J (2000) Chemical-induced hippocampal neurodegeneration and elevations in TNFalpha, TNFbeta, IL-1alpha, IP-10, and MCP-1 mRNA in osteopetrotic (op/op) mice. J Neurosci Res 62:146-55