Abstract
Studies at the basic and clinical levels demonstrate that neuronal atrophy and cell death occur in response to stress and in the brains of depressed patients. Although the mechanisms have yet to be fully elucidated, progress has been made in characterizing the signal transduction cascades that control neuronal atrophy and programmed cell death and that may be involved in the action of antidepressant treatment. These pathways include the cyclic adenosine monophosphate and neurotrophic factor signal transduction cascades. It is notable that these same pathways have been demonstrated to play a pivotal role in cellular models of neural plasticity. This overlap of plasticity and cell survival pathways, together with studies demonstrating that neuronal activity enhances cell survival, suggests that neuronal atrophy and death could result from a disruption of the mechanisms underlying neural plasticity. The role of these pathways and failure of neuronal plasticity in stress-related mood disorders are discussed.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antidepressive Agents / pharmacology
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Antidepressive Agents / therapeutic use
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Atrophy / etiology
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Atrophy / genetics
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Atrophy / pathology
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Brain-Derived Neurotrophic Factor / drug effects
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Brain-Derived Neurotrophic Factor / metabolism
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Cell Death / drug effects
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Cell Death / genetics
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Cell Survival / drug effects
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Cell Survival / genetics
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Cyclic AMP Response Element-Binding Protein / drug effects
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Cyclic AMP Response Element-Binding Protein / metabolism
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Genes, bcl-2 / drug effects
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Genes, bcl-2 / genetics
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Humans
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Mood Disorders* / drug therapy
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Mood Disorders* / etiology
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Mood Disorders* / metabolism
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Neuronal Plasticity / genetics
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Neuronal Plasticity / physiology*
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Neurons / metabolism
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Neurons / pathology*
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Pyramidal Cells / drug effects
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Pyramidal Cells / metabolism
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Receptors, Cyclic AMP / drug effects
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Receptors, Cyclic AMP / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Stress, Psychological / psychology
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Up-Regulation / drug effects
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Up-Regulation / physiology
Substances
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Antidepressive Agents
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Brain-Derived Neurotrophic Factor
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Cyclic AMP Response Element-Binding Protein
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Receptors, Cyclic AMP