Research
In the last several decades we have seen a dramatic increase in the numbers and amount of chemicals that are deposited in our every day environment. There are currently ~80,000 different chemicals being manufactured with ~200 new chemicals being introduced every year. With this rapid rise in toxicant manufacture and use we have begun to take notice of the negative impacts these chemicals have on human health. Indeed, exposure to environmental contaminants has been suggested to be the potential source of many different health concerns, including many neurological disorders. The work in our lab is focused in two areas related to the effect of exposure to environmental toxicants on neurological health. The over arching goal of our research is to elaborate our current knowledge of the neurotoxic effects of the environment and further elucidate the influence of the environment on the etiopathogenesis of neurodegenerative and neurobehavioral disorders.
I. Neurodegenerative Disease
Parkinson’s disease (PD) is a progressive neurodegenerative disease that affects 1% of the population over the age of 55 in the United States. Incidence of PD increases to approximately 4% by age 85. The predominant clinical features of PD are comprised of motor symptoms such as resting tremor, cogwheel rigidity, postural instability, and slowness of movement (bradykinesia), which have been attributed to the degeneration of dopamine-containing neurons in the substantia nigra pars compacta (SNpc) and the striatum, which is the main focus of this application. Exposure to environmental neurotoxicants, such as pesticides as well as other industrial and commercial compounds appears to participate in the etiology and pathogenesis of PD. Extensive laboratory and epidemiological work has shown exposure to the halogenated flame-retardants, polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) can significantly damage the nigrostriatal dopamine system, similar to that seen in PD. As the manufacture and use of both PCBs and PBDEs has been or is currently being restricted, other halogenated flame-retardants, such as chlorinated organophosphates (Cl-OPs), are being produced in larger quantities, ensuring a continued environmental and subsequent human exposure to these compounds for many years to come.
II. Neurodevelopmental Disorders
Neurodevelopment is defined by carefully delineated cellular processes that must precisely occur in order for normal development of the nervous system and subsequent behaviors to emerge. Critical periods of neural development begin in utero and continue throughout childhood and adolescence as neurons are born and migrate to specific brain regions where they differentiate into particular neuronal phenotypes and extend their neurite outgrowths to establish synaptic connections with neighboring neurons. Interference at any point in this process can result in substantial deficits in several neurodevelopmental and neurobehavioral indices, as seen in autism, attention deficit disorder, schizophrenia, etc. Exposure to several environmental toxicants during neurodevelopment, including flame retardants, pesticides, as well as other compounds have been implicated in neuropsychological alterations. Unfortunately, there is a paucity of information related to the developmentally neurotoxic potential, neurological targets, and mechanisms of action of many of these chemicals.
To address these questions we utilize a multi-tiered approach that employs in vitro and in vivo model systems coupled with cellular and molecular neuroscience, neuropathology, and neurobehavior to identify neurologically harmful chemicals and their effects on the nervous system. Our understanding of these chemicals is further enriched by integrating exposure science and epidemiology, which provide a better idea of the depositions and concentrations of specific compounds in the body as well as their relevance to human disease.