Study Led by NICHD Section Chief Suggests Drugs That Activate the NF-α1/FGF2/Neurogenesis Pathway Can Offer New Approach to Depression Therapy

In an article published in the June 2015 issue of Molecular Psychiatry, a scientific team led by senior author Y.Peng Loh, Ph.D., Chief of the Section on Cellular Neurobiology, National Institute of Child Health and Development (NICHD), NIH, reported that neurotrophic factor-α1 [NF-α1, which is also known as carbozxypeptidase E (CPE)] can prevent stress-induced depression through enhancement of neurogenesis and that NF-α1 is activated by rosiglitazone, a drug known to have anti-depressive activity. Major depressive disorder is one of the most common psychiatric illnesses in the United States, and its development is linked to the experience of stressful conditions. Short­term stress, however, is unlikely to be harmful, but prolonged stress may contribute to depression by triggering the release of chemicals that, at sustained, high levels, can kill nerve cells. Recent research indicates that neurotrophic factors and growth factors—naturally occurring substances that promote cell growth—play a role in relieving depression. Scientists suspect they do so by stimulating the generation of new brain cells, a process called neurogenesis. To explore this possibility, Dr. Loh and her team subjected mice to short-term stress and found increased levels of NF-α1, fibroblast growth factor 2 (FGF2), and neurogenesis in the hippocampus, a brain region minvolved in depression. These mice displayed no signs of depression-like behaviors. However, after long-term restraint stress, levels of NF-α1 and FGF2 fell and the mice displayed depression-like behaviors. In a separate set of experiments, mice genetically engineered to lack NF‐α1 had reduced FGF2 and reduced neurogenesis in the hippocampus and showed depression-like behavior. Giving the mice FGF2 reversed the depression.
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