Site-Specific Antidepressant Effects of Repeated Subconvulsive Electrical Stimulation: Potential Role of Brain-Derived Neurotrophic Factor

Gersner, Roman; Tóth, É.; Isserles, Moshe; Zangen, Abraham

doi:10.1016/j.biopsych.2009.09.015

Cited by 103 publications

(59 citation statements)

References 60 publications

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“…CMS in adult rats reduces BDNF expression in the dorsal hippocampus (Grønli et al, 2006;Toth et al, 2008;Gersner et al, 2010) and causes reductions in sucrose preference, sexual behavior, and brain stimulation reward, indicating a state of anhedonia (Muscat and Willner, 1992;Grønli et al, 2006;Toth et al, 2008). Conversely, young rats show resilience to the anhedonic effect of CMS, and, unlike adult rats, their hippocampal BDNF levels remain intact (Toth et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor

Taliaz

Loya²,

Gersner³

et al. 2011

J. Neurosci.

257

168

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Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

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Section: Introductionmentioning

confidence: 99%

Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor

Taliaz

Loya²,

Gersner³

et al. 2011

J. Neurosci.

257

168

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“…Similar to humans, DBS applied to homologous regions in rodents (i.e. the ventromedial prefrontal cortex, vmPFC, and Acb) has been shown to induce antidepressant-like responses in different behavioural tests (Gersner et al, 2010;Hamani et al, 2014Hamani et al, , 2010bHamani and Temel, 2012;Rea et al, 2014).…”

Section: Deep Brain Stimulation (Dbs) Is Currently Being Investigatedmentioning

confidence: 99%

“…In rodents, DBS increases levels of hippocampal serotonin (Adachi et al, 2005;Hamani et al, 2010b) and brain derived neurotrophic factor (Gersner et al, 2010;. In a recent series of studies, stimulation of limbic structures (Encinas et al, 2011;Hamani et al, 2011;Stone et al, 2011;Toda et al, 2008) or the Acb (Schmuckermair et al, 2013) has been shown to increase hippocampal neurogenesis.…”

Section: Deep Brain Stimulation (Dbs) Is Currently Being Investigatedmentioning

confidence: 99%

Acute high frequency stimulation of the prefrontal cortex or nucleus accumbens does not increase hippocampal neurogenesis in rats

Winter

Bregman

Voget

et al. 2015

Journal of Psychiatric Research

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To date, the effects of deep brain stimulation (DBS) on hippocampal neurogenesis have been mainly characterized in the context of memory. Acute stimulation (i.e. for 1 h) of either the entorhinal cortex or the anterior thalamus increases both cell proliferation and survival. We investigate whether stimulation applied to targets being considered for the treatment of depression, namely the ventromedial prefrontal cortex (vmPFC) or nucleus accumbens (Acb), also increases hippocampal neurogenesis in rodents. Rats were treated with vmPFC or Acb DBS for 1 h at different settings. 5′-bromo-2′deoxyuridine (BrdU) was injected three days following stimulation onset and animals were sacrificed 24 h or 28 days later. Overall, we found that neither vmPFC nor Acb DBS increased hippocampal neurogenesis. In summary, the delivery of acute stimulation into targets homologous to those used in human depression trials does not increase hippocampal neurogenesis.

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“…Much has been reported on molecular and cellular changes induced by courses of repeated brief-pulse ECS in both normal rats and rat models for depression and that are believed to be relevant to antidepressant mechanisms, e.g. up-regulation of neurotrophic factors and hippocampal cell proliferation and neurogenesis (Gersner et al, 2010;Madsen et al, 2000;Newton et al, 2003). In contrast, little has been reported on such effects following ultrabrief-pulse ECS.…”

Section: Introductionmentioning

confidence: 99%

“…Finally, the effects of UBP ECS on animal models of depression, in addition to normal rats, need to be studied. For example, BP ECS has been reported to reduce forced swim test immobility time in Flinders Sensitive Line rats (JimenezVasquez et al, 2007), normalise both impaired sucrose preference (a measure for anhedonia) and reduced hippocampal BDNF levels induced by chronic mild stress (Gersner et al, 2010), and reverse corticosterone-mediated inhibition of neurogenesis (Hellsten et al, 2002). It would therefore be important to study the therapeutic effects of UBP ECS in similar models of depression.…”

mentioning

confidence: 99%

A comparison of brief pulse and ultrabrief pulse electroconvulsive stimulation on rodent brain and behaviour

O’Donovan

Kennedy

Guinan

et al. 2012

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Brief pulse electroconvulsive therapy (BP ECT; pulse width 0.5-1.5 msec) is a very effective treatment for severe depression but is associated with cognitive side-effects. It has been proposed that ultrabrief pulse (UBP; pulse width 0.25-0.30 msec) ECT may be as effective as BP ECT but have less cognitive effects because it is a more physiological form of neuronal stimulation. To investigate this further, we treated normal rats with a 10 session course of either BP (0.5 msec), UBP (0.3 msec), or sham electroconvulsive stimulation (ECS) and measured antidepressant-related changes in dentate gyrus cell proliferation and hippocampal BDNF protein levels as well as hippocampal-dependant spatial reference memory using the water plus maze and immobility time on the forced swim test. Both BP and UBP ECS induced very similar types of motor seizures. However, BP ECS but not UBP ECS treatment led to a significant, near 3-fold, increase in cell proliferation (p=0.026) and BDNF levels (p=0.01). In the forced swim test, only BP ECS treated animals had a significantly lower immobility time (p=0.046). There was a trend for similarly reduced hippocampal-dependent memory function in both BP and UBP groups but overall there was not a significant difference between treatment and control animals when tested 10 days after completing allocated treatment. These findings show that, even though both forms of ECS elicited similar motor seizures, UBP ECS was less efficient than BP ECS in inducing antidepressant-related molecular, cellular and behavioural changes.

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Site-Specific Antidepressant Effects of Repeated Subconvulsive Electrical Stimulation: Potential Role of Brain-Derived Neurotrophic Factor

Cited by 103 publications

References 60 publications

Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor

Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor

Acute high frequency stimulation of the prefrontal cortex or nucleus accumbens does not increase hippocampal neurogenesis in rats

A comparison of brief pulse and ultrabrief pulse electroconvulsive stimulation on rodent brain and behaviour

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