Sensitivity to antidepressants linked with TrkB-mediated neural proliferation

Scientists have unveiled a functional link between production of new neurons and the effectiveness of antidepressants (ADs) in an animal model. The study, published by Cell Press in the August 14 issue of the journal Neuron, provides exciting insight into a mechanism that might underlie a poor response to antidepressive medications for anxiety or depression.

Depression is a significant public health problem due to both its high prevalence and its devastating impact on individuals and society," says senior author Dr. Luis F. Parada from the University of Texas Southwestern Medical Center. "Despite much excitement generated by recent advances in the knowledge of brain development and function, the mechanisms underlying the pathogenesis of depression, as well as its amelioration by AD treatment, remain poorly understood."

Animal studies have indicated that chronic treatment with ADs leads to production of new neurons in a part of the brain called the hippocampus. Exercise, such as running, which has a documented positive impact on mental health, also stimulates hippocampal neurogenesis. In both cases, new neurons arise from neural progenitor cells (NPCs) that seem to be required for the behavioral response to ADs.

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Drugs to Grow Your Brain - Compounds that trigger the growth of new brain cells might help treat depression.

Drugs that encourage the growth of new neurons in the brain are now headed for clinical trials. The drugs, which have already shown success in alleviating symptoms of depression and boosting memory in animal models, are being developed by BrainCells, a San Diego-based start-up that screens drugs for their brain-growing power. The company hopes the compounds will provide an alternative to existing antidepressants and says they may also prove effective in treating cognitive disorders, such as Alzheimer's.

"The fact that you might be able to take small molecules to stimulate specific cells to regenerate in the brain is paradigm-shifting," says Christopher Eckman, a neuroscientist at the Mayo Clinic in Jacksonville, FL. "[This approach] takes advantage of the body's innate ability to correct itself when given appropriate cues." Eckman studies compounds that boost brain cell growth in models of neurodegenerative disease and is not involved with BrainCells.

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Antidepressants, Exercise, Age, Even Food Intake, Affect Generation Of New Brain Cells

Recent research shows that the production of new brain cells may be crucial for antidepressants to be effective and that the medication's effectiveness is strongly influenced by age. What's more, meal frequency, type of food, and physical exercise affect the brain's ability to manufacture these new cells.

For the first time in nonhuman primate models, scientists have documented the cause-and-effect relationship between antidepressant drugs and neurogenesis. The researchers found that the antidepressant drug fluoxetine improved the behavior of macaque monkeys with depression-like symptoms.

They also discovered that administering the drugs to normally behaving monkeys did not influence their behavior but did alter their brains by boosting neurogenesis in the hippocampus, an area involved in memory and learning.

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