By selectively activating and inactivating a potent transcription factor in a rat's Nucleus Accumbens (NAc), a main pleasure center in the brain, scientists at the McLean Hospital in Belmont, Mass., might have found a link between cAMP response element-binding protein (CREB) and depression (A.M. Pliakas et al., "Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens," Journal of Neuroscience, 21[18]:7397-403, Sept. 15, 2001). Rat models with elevated expression of CREB in the NAc showed symptoms of dysphoria and despair. Directly blocking CREB activity caused the opposite effect, making the rats react as if they were treated with antidepressant drugs. Says William Carlezon, director of McLean's Behavioral Genetics laboratory: "Our data indicate that activation of CREB might be an early step in triggering depression symptoms." CREB, a transcription factor, enables activation of many genes in the brain. One effect of CREB activation is increased production of the opioid peptide dynorphin, known as the "evil cousin" of endorphin, which is responsible for "runner's high." "Like endorphin, dynorphin is also a pain killer, but it makes you feel lousy rather than good," says Carlezon. The study shows that blocking the brain's dynorphin receptors significantly decreases depression symptoms that occur with elevated levels of CREB in NAc. This link could lead to new treatments for depressions, but Carlezon emphasizes it's still early in the process. Medicinal chemists, he says, are working to efficiently deliver dynorphin blockers into the brain.
Autism Study to Use MRI on Children
The Autism Research Project at the University of North Carolina at Chapel Hill and Duke University Medical Center has begun a collaborative study designed to identify and examine the changes in brain development of young children with respect to autism. Autistic and non-autistic children between 18 and 35 months old will have their brains scanned using magnetic resonance imaging (MRI); the test will be repeated 24 months later. Funded by the National Institutes of Health, the study is designed to build on previous brain development work in autistic children. "We've seen a couple of studies where the brain in our subjects seemed to be larger than normal, says Joseph Piven, director of UNC's Neurodevelopmental Disorders Research Center. "Ages 2 through 4 are a very formative time span in brain development." The study's longitudinal approach is significant. Says Piven: "Examining this particular age group is much more powerful than if we were to scan a wider age range." This study could provide clues to the underlying reasons behind autism on the cellular level and how to study the brain more completely. "Autism is a mixed bag--there are a lot of probable causes for it," he says. "If we are able to generate a subgroup from this phenotype, we may be able to determine the genes responsible." Currently there are no brain atlases of children this age. Piven hopes to make the information from this study available to the public.
