Targeting neurotrophic/growth factor expression and signaling for antidepressant drug development.
Preclinical and clinical studies have demonstrated that stress and depression result in cell atrophy and loss in limbic and cortical brain regions while antidepressants reverse these effects. In concert with these findings, reduced expression of numerous genes that mediate neurotrophin and growth factor signaling has been observed in depressed patients and in stressed animals. Further, antidepressants are known to elevate the expression of multiple genes involved in these signaling pathways. Together, these findings have implicated neurotrophic factors in both the etiology and treatment of depression. Below we review the current data supporting the neurotrophic hypothesis of depression, and discuss potential approaches to pharmacologically upregulate neurotrophic/growth factor signaling to elicit antidepressant responses.
Tanis
Keith Q
KQ
Division of Molecular Psychiatry, Abraham Ribibcoff Research Facilities, Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06508, USA. ronald.duman@yale.edu
Newton
Samuel S
SS
Duman
Ronald S
RS
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000494:pharmacology; D003863:Depression / Q000378:metabolism; D006801:Humans; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D017475:Receptors, Nerve Growth Factor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000928:Antidepressive Agents; D017362:Cyclic AMP Response Element-Binding Protein; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor