Brain Protein Counters Despair

Mice that are more resilient when faced with inescapable stress can thank a brain protein called ΔFosB, according to Eric J. Nestler of the University of Texas Southwestern Medical Center and colleagues (Neuron 2007, 55, 289). When mice are repeatedly exposed to random shocks, some eventually stop trying to escape and sink into despair. This state bears a similarity to human depression. The researchers found that mice that avoided despair and retained a strong desire to escape had higher brain levels of ΔFosB. The researchers also showed that increasing expression of ΔFosB in the brains of mice reduced symptoms of despair. The despair-reducing protein, a transcription factor that regulates the activity of multiple genes, appears to inhibit passive response to stress. The researchers will now explore whether antidepressants, which can reverse despair in mice, enhance resilience by boosting ΔFosB.