This project was initiated this year due to the multidisciplinary interest of various investigators at NIEHS. Over the last few years, interactions between the immune system and the nervous system have become well established if not yet understood. These interactions may be direct, indirect, via the Hypothalamic-Pituitary-Adrenal Axis or vis the resident immune cells of the brain. There have been a number of proposed links between the immune system and the nervous system (and possible interactions with the reproductive system) including: 1) prolonged post-natal development/maturation of both systems. 2) infection in the pregnant mother and possible transfer of infection to the offspring or the transfer of factors of the pro-inflammatory cascade (TNFalpha, Interleukin-6) to the offspring and long-term effects on the child as related to an immune-mediated response. 3) the transfer of active virsus into the brain (e.g., Herpes, HIV, West-Nile) and the manifestation of cognitive deficits/dementia. 4) the increased occurrance of cognitive deficits in human cases related to autoimmune disease (e.g., AIDs, Multiple Sclerosis, Tryptophan-induced autoimmunity), 5) the lack of success with therapeutic intervention with anti-inflammatory agents for cognitive impairment suggesting a more complicated interactions between the systems than previously anticipated. Within the framework of exposure to environmental agents, there exists a substantial data base to suggest that acute responses of the immune system can occur as a result of chemical exposure. Additional efforts are underway within NIEHS to generate such information of the developing immune system. Quite often, the agents or factors that have the capacity to alter the immune system are shown to also alter the nervous system. Thus, it is the purpose of this project to attempt to identify interactions between the two systems that may contribute not only to acute adverse effects but also to long-term adverse outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES101623-02
Application #
7007545
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2004
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
Goulding, David R; White, Sally S; McBride, Sandra J et al. (2017) Gestational exposure to perfluorooctanoic acid (PFOA): Alterations in motor related behaviors. Neurotoxicology 58:110-119
Avdoshina, Valeria; Caragher, Seamus P; Wenzel, Erin D et al. (2017) The viral protein gp120 decreases the acetylation of neuronal tubulin: potential mechanism of neurotoxicity. J Neurochem 141:606-613
Orihuela, Ruben; McPherson, Christopher A; Harry, Gaylia Jean (2016) Microglial M1/M2 polarization and metabolic states. Br J Pharmacol 173:649-65
Szabo, Steven T; Harry, G Jean; Hayden, Kathleen M et al. (2016) Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer's Disease and Nondemented Elderly Controls. Toxicol Sci 150:292-300
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
McPherson, C A; Merrick, B A; Harry, G J (2014) In vivo molecular markers for pro-inflammatory cytokine M1 stage and resident microglia in trimethyltin-induced hippocampal injury. Neurotox Res 25:45-56
Harry, G Jean; Hooth, Michelle J; Vallant, Molly et al. (2014) Developmental neurotoxicity of 3,3',4,4'-tetrachloroazobenzene with thyroxine deficit: Sensitivity of glia and dentate granule neurons in the absence of behavioral changes. Toxics 2:496-532
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

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