(Beyond Pesticides, February 8, 2007) Investigators at St. Jude Children’s Research Hospital have shed new light on the suspected role of pesticides in the development of Parkinson’s disease (PD). The study, “GST expression mediates dopaminergic neuron sensitivity in experimental parkinsonism” appearing in the Proceedings of the National Academy of Sciences (January 31, 2007), illustrates the mechanism of nerve cell damage by pesticide exposure.
The enzyme that prevents damage to the substantia nigra, the part of the brain where nerve cell damage associated with PD occurs, is called GST pi (“pie”). This enzyme stands like a sentry at the crossroads of several biochemical pathways, any one of which can lead to PD. GST pi protects the nerve cell from death caused by either environmental toxics, such as pesticides, or a self-destruction process called apoptosis (cell suicide), triggered by certain stressful conditions in the cell. If GST pi levels are reduced or this enzyme is overwhelmed by toxics, these nerves are at increased risk of death, according to studies in mouse models.
GST pi is one of a family of similar enzymes that eliminate free radicals generated by pesticides and other chemicals. Two members of this family are present in the brain, but only one of them, GST pi, is found in the dopaminergic neurons of the substantia nigra. When nerve cells in the substantia nigra region of the brain die, it results in a loss of dopamine, the nerve-signaling molecule that helps control muscle movement. The absence of dopamine from these cells, called dopaminergic neurons, causes the loss of muscle control, trembling and lack of coordination exhibited in PD.
The study explains the cause of most cases of PD. “The majority of these cases of Parkinson’s disease appear to arise because individuals who have a genetic susceptibility to the disease are exposed to environmental toxins such as pesticides and herbicides, which trigger the formation of free radicals that kill dopaminergic neurons in the substantia nigra,” according to Richard Smeyne, Ph.D., an associate member of the Department of Developmental Neurobiology at St. Jude and the report’s senior author.
In conducting the investigation, which led to these findings, the scientists treated mice with the substance MPTP, a by-product of a heroin substitute, in order to determine if levels of GST pi changed. MPTP is a mitochondrial complex 1 inhibitor as is the pesticide rotenone, a naturally occuring material used in organic production and products, that is also implicated in PD (Beyond Pesticides, November 8, 2004). Rotenone is used in common household garden products such as Garden Dust for insect control, for lice and tick control on pets, and for fish eradication. MPTP’s chemical structure also resembles that of the restricted-use herbicide paraquat. (Beyond Pesticides, January 22, 2002).
According to the British Medical Journal (January 22, 2007), many studies have found an association between pesticides and PD, but no one agent has been consistently identified. Those implicated include organochlorine insecticides (dieldrin), maneb and paraquat. Other researchers have documented low-dose effects of the insecticide permethrin, doses below one-one thousandth of a lethal dose for a mouse, on those brain pathways involved in PD. The effects are consistent with a pre-parkinsonsian condition, but not yet full-blown parkinsonism (Beyond Pesticides, March 31, 2003).
While researchers point to this discovery as helpful in risk assessment and therapeutic remedies, the medical community should equally promote reducing your exposure to pesticides as a preventative method.