Investigators at UT Southwestern Medical Center found that the inhibition of brain-derived neurotrophic factor (BDNF) and specific gene alterations in potassium channels improve mice’s ability to handle stress.
The scientists used genetically identical male mice. They stressed the rodents by placing them in the territory of a larger, aggressive mouse and recorded how this affected their ability to interact socially.
The UT Southwestern team says that some mice interacted with the unfamiliar, more aggressive mouse, while others avoided it and showed submissive behavior.
The researchers then examined two areas of the brain that are associated with pleasure and reward, called the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Neurons in the VTA send chemical signals to the NAc.
The investigators report finding that in mice experiencing social defeat and depression, these neurons fire faster. Upon firing, the neurons cause the release of BDNF leading to an increase of the protein in the NAc. When BDNF was blocked in the more timid mice, they became resistant to stress, according to the research team.
The scientists also discovered that mice who coped better had different gene expression in the VTA and NAc than vulnerable mice. Three of the genes that showed the greatest difference between the two groups reportedly coded for potassium channels. The researchers found that the resilient animals had increased activity of the potassium channels, which counters the rise in nerve firing and hence the increase of BDNF release.
To explore how these results might apply to humans, the investigators obtained brain samples from depressed and nondepressed humans. The depressed people showed a 40% increase in BDNF levels in their NAc, compared to controls.
The study appears in the October 19 issue of Cell.