Brain-derived neurotrophic factor and its receptor tropomyosin-related kinase B in the mechanism of action of antidepressant therapies.
The focus of this review is to critically examine and review the literature on the role of brain-derived neurotrophic factor (BDNF) and its primary receptor, tropomyosin-related kinase B (TrkB), in the actions of pharmacologically diverse antidepressant treatments for depression. This will include a review of the studies on the regulation of BDNF and TrkB by different types of antidepressant drug treatments and animal in models of depression, as well as altered levels of BDNF and TrkB in the blood and postmortem brain of patients with depression. Results from clinical and basic studies have demonstrated that stress and depression decrease BDNF expression and neurogenesis and antidepressant treatment reverses or blocks these effects, leading to the neurotrophic hypothesis of depression. Clinical studies demonstrate an association between BDNF levels and several disorders, including depression, epilepsy, bipolar disorder, Parkinson's and Alzheimer's diseases. Physical activity and diet exert neurotrophic effects and positively modulate BDNF levels. A common single nucleotide polymorphism (SNP) in the BDNF gene, a methionine substitution for valine, is associated with alterations in brain anatomy and memory, but what role it has in clinical disorders is unclear. Findings suggest that early childhood events and adult stress produce neurodegenerative alterations in the brain that can eventually cause breakdown of information processing in the neuronal networks regulating mood. Antidepressant treatments elevate activity-dependent neuronal plasticity by activating BDNF, thereby gradually restoring network function and ultimately mood.
Kozisek
Megan E
ME
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5800, United States. megankozisek@yahoo.com
Middlemas
David
D
Bylund
David B
DB
D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism*; D002648:Child; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000188:drug therapy; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D019964:Mood Disorders / Q000188:drug therapy; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism*
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB