Molecular and cellular actions of chronic electroconvulsive seizures.
Recent studies have begun to examine the influence of electroconvulsive shock (ECS) on the expression of growth factors in brain, as well as alterations in the function and structure of certain populations of neurons. These studies demonstrate that long-term ECS increases the expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in limbic brain regions. BDNF, a member of the nerve growth-factor family, has been shown to increase the synaptic strength, survival, and growth of adult neurons. Studies in vivo and in cultured cells indicate that the induction of BDNF and TrkB is mediated by the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), a transcription factor that is activated by cAMP and Ca2+ intracellular pathways. Chronic ECS is also reported to induce sprouting of hippocampal neurons, and studies in BDNF mutant mice indicated that this sprouting is partially dependent on upregulation of BDNF. Increased expression of BDNF and sprouting could also contribute to the altered electrophysiologic properties of hippocampal neurons. These effects of chronic ECS are discussed with respect to recent studies demonstrating that the pathophysiology of stress and depression involves atrophy or death of hippocampal neurons. This work has led to the hypothesis that ECS and antidepressant drugs, via regulation of neurotrophic factors, reverse the atrophy of stress-vulnerable neurons or protect these neurons from further damage.
Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, New Haven 06508, USA.
R S
RS
Duman
V A
VA
Vaidya
D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001923:Brain Chemistry / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D004565:Electroconvulsive Therapy; D006801:Humans; D051379:Mice; D009474:Neurons / Q000473:pathology / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor