Review : Stress, Antidepressant Treatments, and Neurotrophic Factors: Molecular and Cellular Mechanisms

Abstract

Repeated stress or an excess of glucocorticoids can exacerbate neuronal damage in response to insults and, in severe cases, can lead to neuronal atrophy and death. These effects are thought to be related to the actions of stress and glucocorticoids on glutamate function, neuronal metabolism, and the generation of cytotoxic free radicals. Recent studies demonstrate that the regulation of neurotrophic factors may contribute to the actions of stress on neuronal function. Acute or chronic stress decreases the expression of brain derived neurotrophic factor, the most abundant neurotrophin in the brain, in specific regions of the hippocampus, and other forebrain regions. In addition, chronic stress increases the expression of neurotrophin-3 in certain regions of the hippocampus and may, thereby, help to protect these regions from the neurotoxic effects of chronic stress. The deleterious effects of stress may contribute to psy�chiatric illnesses, such as depression, that can be precipitated or worsened by stress and that are often characterized by hypercortisolism. Electroconvulsive seizure therapy, as well as antidepressant drugs, increase the expression of brain derived neurotrophic factor and its receptor, trk B, in the brain, demon�strating that neurotrophins are a target of antidepressant treatments. These findings outline a role of neurotrophic factors in the etiology and treatment of certain psychiatric illnesses. The Neuroscientist 1:351-360, 1995.