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Cell Death In Sparrow Brains May Provide Clues In Age-related Human Diseases
Science Daily — A remarkable change takes place in the brains of tiny 
songbirds every year, and some day the mechanism controlling that change may 
help researchers develop treatments for age-related degenerative diseases of 
the brain such as Parkinson's and dementia. 

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Writing in the Proceedings of the National Academy of Sciences, researchers 
from the University of Washington and the University of California, Berkeley, 
report a striking shrinkage in the size of the brain regions that control 
singing behavior of Gambel's white-crowned sparrows. 
This transformation is triggered by the withdrawal of testosterone, a 
naturally occurring steroid hormone, and is apparent within 12 hours. The 
study is the first to report such rapid regression of brain nuclei caused by 
the withdrawal of a hormone and a change in daylight conditions in adult 
animals. 
"The changes are substantial," said Christopher Thompson, lead author of the 
study and a UW doctoral student in neurobiology and behavior. "First, the 
volume of a song-control region called the HVC collapses 12 hours after 
testosterone is removed from circulation. Then, by four days, thousands of 
HVC neurons are lost. We have good reason to believe that they are killed by 
a cell suicide program call apoptosis." 
Co-authors of the study are Eliot Brenowitz, a UW professor of psychology and 
biology, and George Bentley, a former UW postdoctoral researcher who is now a 
UC Berkeley assistant professor of integrative biology. 
The research mimicked the natural seasonal changes that occur in the brains of 
the sparrows. Their song-control regions expand in the spring and summer 
leading up to the breeding season, as they use songs to establish territories 
and attract mates in Alaska. Later in the summer, as the birds get ready to 
migrate back to California, the same brain regions shrink. 
"We've seen seasonal changes in the brains of fish, reptiles, amphibians, 
birds and mammals such as gerbils, mice, and even in humans," said 
Brenowitz. "However, the magnitude of changes in birds far exceeds that seen 
in other animals." 
To better understand what happens in the sparrows' brain, the researchers 
received federal and state permits to capture 25 of the migrating male birds 
in Eastern Washington. Next, they housed the birds for 12 weeks before 
exposing them to 20 days of long-day conditions comparable to the natural 
lighting the sparrows would experience in Alaska during the breeding season. 
The birds were also implanted with testosterone. 
At the end of 20 days, six of the birds were euthanized and the remaining 19 
were castrated and testosterone implants were removed so there would not be 
any circulating testosterone in their systems. After 12 hours five more birds 
were euthanized and the remainder were euthanized at 2, 4, 7 and 20 days. 
These procedures were done with the approval of the UW's Institutional Animal 
Care and Use Committee and the National Institute of Mental Health. The 
latter funded the research. 
The researchers found that the size of the HVC region decreased 22 percent 
within 12 hours after the withdrawal of testosterone and that the number of 
neurons in this song-control region fell by 26 percent after four days. In 
addition, the size of two other song-control regions called Area X and the RA 
significantly regressed after 7 and 20 days, respectively. 
Thompson said there are a number of potential medical implications relating to 
age-related degenerative diseases and conditions marked by declining mental 
abilities from this study. 
"Having an animal model system with such robust neurodegeneration could be 
very useful in uncovering the mechanisms that underlie these kinds of 
diseases," he said. "We will be looking at the molecular mechanisms of what 
happens when testosterone is removed. As men age, circulating levels of 
testosterone decrease, and other researchers have shown that this decline may 
contribute to cognitive impairment, brain disorders and neuron death." 
Brenowitz added: "There is no reason to think that these processes are 
restricted to birds. They are very similar to what happens in some mammals. 
This study shows that regions of the brain that are hormonally sensitive are 
going to regress without testosterone. The flip side is that hormones such as 
testosterone protect neurons, so perhaps some form of hormone therapy may 
provide protection. Steroids such as testosterone are very potent and have 
wide implications for effects on the brain." 
Note: This story has been adapted from a news release issued by University of 
Washington.

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