Credit: Frank Leung

Like college students who complete an exam and then promptly forget everything they studied, male songbirds 'forget' their songs when they no longer need them to attract mates. When breeding season ends, the region in birds' brains that controls song (called the HVC) shrinks, and neurons in the area begin to die in massive quantities. A new study by Christopher Thompson and Eliot Brenowitz (University of Washington, Seattle) may shed light on the mechanisms of this degeneration process. By inhibiting the activity of enzymes called caspases, which are known to be involved in cell suicide, the researchers managed to prevent HVC regression and neuron death. Their findings may be useful for treatment of neural degenerative diseases such as Alzheimer's and Parkinson's.

The authors built on previous studies showing that seasonal growth and regression of the neural song control system are directly correlated with the concentration of testosterone circulating in the body. The team captured and later castrated wild Gambel's white-crowned sparrows (J. Neurosci. 28, 7130–7136; 2008). To simulate breeding conditions and induce maximum growth of the HVC, they implanted birds with testosterone capsules and exposed them to long photoperiods (20 h light per day). A few days later, the scientists implanted cannulas into one side of birds' brains, near the HVC. They connected the cannulas to osmotic pumps, which birds wore like 'backpacks' between their wings. Some of the osmotic pumps delivered caspase inhibitors to birds' brains, whereas others delivered a control substance. The researchers then simulated the end of the breeding season by removing birds' testosterone implants and gradually shortening the photoperiod to 8 h.

Thompson and Brenowitz euthanized groups of sparrows 1, 3 and 7 d after beginning testosterone withdrawal and analyzed their brain tissue. In all cases, birds that received caspase inhibitors showed significantly less HVC regression on the side of the brain in which the cannula had been implanted, compared with the other side of the brain. Birds that received the control substance also showed substantial neuronal death.

Notably, the caspase inhibitors managed to prevent deterioration in a second brain region that was connected to the HVC, on the same side as the cannula. This finding may have implications for stroke victims, Brenowitz notes, as studies have shown that stroke-related degeneration occurs not only in areas of the brain that are directly affected by the loss of blood supply, but in connected neural regions as well.