Leptin, the product of ob gene, plays an important role in regulating body weight. Defects in the production of active leptin, like those observed in homozygous mutant (ob/ob) or the leptin-receptor deficient (db/db) mice, leads to increased appetite, decreased energy expenditure and weight gain, resulting in obesity. Obesity is a major risk factor associated with a variety of human disorders. While its involvement in diseases such as diabetes, coronary heart disease and cancer have been well characterized, it remains to be unraveled if obesity modulates the responses of the nervous system to insults. In the present study, an attempt has been made to determine if obesity may be an underlying risk factor in neurodegenerative disorders. Model neurotoxicants, methamphetamine (METH) and kainic acid (KA), known to cause selective neurodegeneration of anatomically distinct areas of the brain, were evaluated using a mouse model of obesity, the ob/ob mice.
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California