Repeated electroconvulsive seizures increase the total number of synapses in adult male rat hippocampus

Chen, Fenghua; Madsén, Torsten; Wegener, Gregers; Nyengaard, Jens Randel

doi:10.1016/j.euroneuro.2008.12.007

Cited by 139 publications

(112 citation statements)

References 64 publications

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“…Both ECS and EE ameliorate depressionlike behavior in rodents and seem to employ similar mechanisms to exert their antidepressant effects [21,58]. They alter gene expression profiles [59][60][61], increase adult neurogenesis [21,62,63], and positively affect synaptic plasticity [22,23,64,65]. These processes may be partly mediated through the induction of particular neurotrophic factors that are, according to the neurotrophic depression theory, reduced in the depressed brain [59,60,[66][67][68].…”

Section: Discussionmentioning

confidence: 92%

Kdm6b and Pmepa1 as Targets of Bioelectrically and Behaviorally Induced Activin A Signaling

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Kurinna²,

Havlicek

et al. 2015

Mol Neurobiol

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The transforming growth factor-β (TGF-β) family member activin A exerts multiple neurotrophic and protective effects in the brain. Activin also modulates cognitive functions and affective behavior and is a presumed target of antidepressant therapy. Despite its important role in the injured and intact brain, the mechanisms underlying activin effects in the CNS are still largely unknown. Our goal was to identify the first target genes of activin signaling in the hippocampus in vivo. Electroconvulsive seizures, a rodent model of electroconvulsive therapy in humans, were applied to C57BL/6J mice to elicit a strong increase in activin A signaling. Chromatin immunoprecipitation experiments with hippocampal lysates subsequently revealed that binding of SMAD2/3, the intracellular effectors of activin signaling, was significantly enriched at the Pmepa1 gene, which encodes a negative feedback regulator of TGF-β signaling in cancer cells, and at the Kdm6b gene, which encodes an epigenetic regulator promoting transcriptional plasticity. Underlining the significance of these findings, activin treatment also induced PMEPA1 and KDM6B expression in human forebrain neurons generated from embryonic stem cells suggesting interspecies conservation of activin effects in mammalian neurons. Importantly, physiological stimuli such as provided by environmental enrichment proved already sufficient to engender a rapid and significant induction of activin signaling concomitant with an upregulation of Pmepa1 and Kdm6b expression. Taken together, our study identified the first target genes of activin signaling in the brain. With the induction of Kdm6b expression, activin is likely to gain impact on a presumed epigenetic regulator of activity-dependent neuronal plasticity.

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Section: Discussionmentioning

confidence: 92%

Kdm6b and Pmepa1 as Targets of Bioelectrically and Behaviorally Induced Activin A Signaling

Link

Kurinna²,

Havlicek

et al. 2015

Mol Neurobiol

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“…Adult neuro genesis has been shown to occur after both ECS and epileptic seizures in animals. 52,53 Thus, decreases in NAA with ECT may point to changes in the ratio of mature to im mature neurons, which may reflect enhanced adult neuro genesis, as has been linked with MDD and treatment re sponse in a growing number of studies. 50 Notably, studies have also shown that many adultborn neurons within the hippocampal dentate gyrus integrate into preexisting limbic circuitry to ultimately acquire electrophysiological character istics of mature neurons.…”

Section: J Psychiatry Neurosci 2017;42(1)mentioning

confidence: 99%

Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression

Njau

Joshi

Espinoza

et al. 2017

JPN

112

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“…Our current understanding is that the antidepressant effect of ECT is partially mediated by seizure-induced neurotrophic effects, resulting in increased rates of neurogenesis, synaptogenesis, and glial proliferation, particularly in the hippocampus (3)(4)(5). Modern neuroimaging experiments have shown a critical role for the subgenual cortex (Brodmann area 25) (6) and deep brain stimulation of this area also results in alleviation of symptoms (7,8).…”

mentioning

confidence: 99%

Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders

Dukart

Regen

Kherif

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

139

126

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There remains much scientific, clinical, and ethical controversy concerning the use of electroconvulsive therapy (ECT) for psychiatric disorders stemming from a lack of information and knowledge about how such treatment might work, given its nonspecific and spatially unfocused nature. The mode of action of ECT has even been ascribed to a "barbaric" form of placebo effect. Here we show differential, highly specific, spatially distributed effects of ECT on regional brain structure in two populations: patients with unipolar or bipolar disorder. Unipolar and bipolar disorders respond differentially to ECT and the associated local brain-volume changes, which occur in areas previously associated with these diseases, correlate with symptom severity and the therapeutic effect. Our unique evidence shows that electrophysical therapeutic effects, although applied generally, take on regional significance through interactions with brain pathophysiology.magnetic resonance imaging | voxel-based morphometry | unipolar depression | hippocampus E lectroconvulsive therapy (ECT) is the oldest well-established procedure for somatic treatment of unipolar and bipolar disorders (1); however, its precise mechanism of action is still unclear (2). Our current understanding is that the antidepressant effect of ECT is partially mediated by seizure-induced neurotrophic effects, resulting in increased rates of neurogenesis, synaptogenesis, and glial proliferation, particularly in the hippocampus (3-5). Modern neuroimaging experiments have shown a critical role for the subgenual cortex (Brodmann area 25) (6) and deep brain stimulation of this area also results in alleviation of symptoms (7,8). Concerns regarding structural brain damage caused by ECT have been largely attenuated because of a lack of experimental evidence for ECT-induced neuronal damage (9). The scarce in vivo evidence for ECT-induced structural brain plasticity comes from region-of-interest (ROI) imaging studies reporting ECT-related hippocampal volume increases (10) that correlate with clinical outcome (11,12). Limited by an ROI approach and a lack of adequate control groups, these studies may have incompletely detected the effects of right unilateral ECT and failed to distinguish them from pharmacologically induced changes or indeed the effects of disease.We decided to resolve these ambiguities by carrying out a study with drug responsive (no-ECT) and drug-resistant (ECT) patients with either uni-or bipolar depression ( Fig. 1 and Table 1). The two psychiatric conditions are considered separate from pathophysiological and nosological viewpoints. A group of normal volunteers was included to control for non-ECT-associated confounds and to provide a way of assessing ECT-associated therapeutic effects. All subjects were recruited and imaged using structural magnetic resonance at entry (time point 1, TP1). If unresponsive to drugs, patients had ECT administered unilaterally to the right hemisphere. All study participants were imaged again at 3 mo (TP2) and 6 mo (TP3). ECT was giv...

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Repeated electroconvulsive seizures increase the total number of synapses in adult male rat hippocampus

Cited by 139 publications

References 64 publications

Kdm6b and Pmepa1 as Targets of Bioelectrically and Behaviorally Induced Activin A Signaling

Kdm6b and Pmepa1 as Targets of Bioelectrically and Behaviorally Induced Activin A Signaling

Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression

Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders

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