UC Davis

The global obesity epidemic cannot be attributed solely to high caloric intake and inactivity. Recent systematic reviews and meta-analyses suggest a correlation between exposure to the insecticide DDT/ DDE and elevated body fat, reduced energy expenditure, and heightened obesity risk. There is evidence that these effects of DDT/DDE are mediated by a decrease in brown adipose tissue (BAT) thermogenesis, which is under the regulatory influence of the sympathetic nervous system. A recent study found that developmental exposure to DDT and DDE decreased sympathetic innervation of BAT and decreased synaptic density in peripheral sympathetic ganglia, suggesting a possible mechanism by which DDT and DDE exposure during development increases risk of obesity. To determine whether these changes to sympathetic morphology observed in vivo are due to direct effects of DDT on sympathetic neurons, we exposed primary sympathetic neurons derived from embryonic rat superior cervical ganglia (SCG) to p,p’-DDT and its main metabolite p,p’-DDE and measured axonal and dendritic morphology. At the concentrations tested (0.01 to 1 µM), neither DDT nor DDE altered the number of axons and dendrites per neuron. However, DDT significantly reduced axonal length in both male and female sympathetic neurons at 1 µM and 0.1 µM, respectively. Both DDT and DDE significantly reduced BMP-7-induced dendritic outgrowth in male neurons at concentrations greater than 0.1 µM and in female neurons at all concentrations that were tested. In cultures not exposed to BMP-7, neither DDT nor DDE altered dendritic growth. These morphological effects of DDT and DDE occurred at concentrations that did not decrease cell viability, as assessed by calcein uptake and release of lactate dehydrogenase into the culture media. Collectively, these data demonstrate that DDT and DDE have a direct effect on morphology of sympathetic neurons with female neurons being more sensitive to exposure than neurons from male rats and dendrites being more vulnerable to DDT and DDE exposure than axons in both sexes.