 |
|
|
|
Mona
Thiruchelvam, PhD |
| Title: Assistant Professor |
| Affiliation: Rutgers, The State University of NJ |
| Department:
Pharmacology and Toxicology |
| Research Interests:
|
|
Dr. Mona Thiruchelvam’s lab is interested in understanding the pathogenesis of Parkinson’s disease. Parkinson’s disease (PD) is a neurodegenerative disorder associated with aging that results from progressive degeneration of dopaminergic neurons in the substantia nigra. Although several risk factors have been postulated to contribute to sporadic PD, including genetic background, environmental chemical exposures and the aging process, its etiology remains unknown. In fact no one risk factor can solely account for this disease, lending support to the emerging hypothesis that it may be multifactorial in origin, resulting from an interaction among various risk factors. We have developed an environmentally relevant exposure model, based on exposure to a combination of pesticides, i.e., paraquat (PQ) and maneb (MB). The effects produced by PQ+MB are selective for the nigrostriatal dopaminergic system and appear to be permanent. Additionally, this exposure to PQ+MB produces an age-related effect, with older animals being more susceptible. Moreover, we have shown that a genetic predisposition increases susceptibility to pesticide exposures. Although a developmental basis for PD has been proposed, it remains largely unexplored. We have developed a model that provides compelling support for such a possibility, where postnatal PQ+MB exposure not only produces permanent and selective nigrostriatal dopaminergic neurotoxicity, it also markedly enhances vulnerability to subsequent pesticide exposures in adulthood, and most importantly leads to progressive loss of dopaminergic neurons with age. This model of PD possesses advantages not found in current animal models, in particular its progressive nature, and is especially important in testing potential therapeutic interventions. Furthermore, all these findings show a gender bias, with males always more vulnerable compared to females, an observation consistent with the human epidemiology. Current efforts are focused on identifying and understanding the target sites implicated in the neuroprotection in females, with the hope of developing specific neuroprotective agents. Additionally, we are also interested in understanding the specific mechanisms associated with selective degeneration of the dopaminergic neurons in our animal model.
|
|
| |
|
|
|
