Neuronal plasticity and survival in mood disorders.
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.
Duman
R S
RS
Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut 06508, USA.
Malberg
J
J
Nakagawa
S
S
D'Sa
C
C
D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001284:Atrophy / Q000209:etiology / Q000235:genetics / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D019254:Genes, bcl-2 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019964:Mood Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011953:Receptors, Cyclic AMP / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000523:psychology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D011953:Receptors, Cyclic AMP