During the development of the nervous system, the temporal and spatial regulation of gene expression is a critical component of neural and glial growth, development, and interactions. These critically timed events are assummed to be a major component in the differential susceptibility of the developing organism to environmental insult.This project examined chemical induced perturbations during development of the NS as indicated by alterations in the spatio-temporal expression of mRNA for various developmentally regulated proteins associated with distinct processes of development. The developmental related effects of chemicals which disrupt thyroid hormone levels are examined to determine specific effects on neuronal and myelin related genes in the development of the nervous system. In addition, thyroid altering agents are examined not only with reference to gene expression during critical periods of development but also in relationship to the development of the neural network as determined both immunohistochemically and Golgi staining. Additional studies are ongoing to determine the role of Il-6 in nervous system development and the adverse effects on the functioning of the nervous system following acute developmental exposure to hyper Il-6.These studies examine the acute toxicity of interleukin 6 on the early post-natal developing CNS and alteration in the normal ontogeny of molecular markers for cortical neuronal network development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021164-05
Application #
6542810
Study Section
(LT)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2001
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
McPherson, Christopher A; Zhang, Guozhu; Gilliam, Richard et al. (2018) An Evaluation of Neurotoxicity Following Fluoride Exposure from Gestational Through Adult Ages in Long-Evans Hooded Rats. Neurotox Res 34:781-798
Orihuela, Ruben; McPherson, Christopher A; Harry, Gaylia Jean (2016) Microglial M1/M2 polarization and metabolic states. Br J Pharmacol 173:649-65
Kraft, Andrew D; McPherson, Christopher A; Harry, G Jean (2016) Association Between Microglia, Inflammatory Factors, and Complement with Loss of Hippocampal Mossy Fiber Synapses Induced by Trimethyltin. Neurotox Res 30:53-66
Harry, G Jean (2013) Microglia during development and aging. Pharmacol Ther 139:313-26
Harry, G Jean; Kraft, Andrew D (2012) Microglia in the developing brain: a potential target with lifetime effects. Neurotoxicology 33:191-206
Kraft, Andrew D; Kaltenbach, Linda S; Lo, Donald C et al. (2012) Activated microglia proliferate at neurites of mutant huntingtin-expressing neurons. Neurobiol Aging 33:621.e17-33
Kraft, Andrew D; Harry, G Jean (2011) Features of microglia and neuroinflammation relevant to environmental exposure and neurotoxicity. Int J Environ Res Public Health 8:2980-3018
McPherson, C A; Aoyama, M; Harry, G J (2011) Interleukin (IL)-1 and IL-6 regulation of neural progenitor cell proliferation with hippocampal injury: differential regulatory pathways in the subgranular zone (SGZ) of the adolescent and mature mouse brain. Brain Behav Immun 25:850-62
Brock, Brian; Basha, Riyaz; DiPalma, Katie et al. (2008) Co-localization and distribution of cerebral APP and SP1 and its relationship to amyloidogenesis. J Alzheimers Dis 13:71-80
Zhang, Donghui; Harry, G Jean; Blackshear, Perry J et al. (2008) G-protein pathway suppressor 2 (GPS2) interacts with the regulatory factor X4 variant 3 (RFX4_v3) and functions as a transcriptional co-activator. J Biol Chem 283:8580-90

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