Electroconvulsive seizure increases adult hippocampal angiogenesis rats

Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, USA.
European Journal of Neuroscience (Impact Factor: 3.67). 09/2006; 24(3):819-28. DOI: 10.1111/j.1460-9568.2006.04958.x
Source: PubMed

ABSTRACT Electroconvulsive seizure has a proven therapeutic application in the treatment of severe depression and treatment-resistant depression. Despite the efficacy of electroconvulsive seizure as a non-chemical antidepressant treatment, the mechanism of action is unclear. Elevation in hippocampal trophic factor expression and concomitant cellular proliferation are thought to play a role in its action. We examined whether the reported induction of angiogenic factors and endothelial cell proliferation leads to an increase in vascular density. Two hippocampal regions, the dentate gyrus and the stratum lacunosum moleculare (SLM), were examined employing a combination of vascular density quantification, angiogenic gene expression analysis and immunohistochemistry. A 6% increase in vascular density was observed in the dentate gyrus but this did not achieve statistical significance. The SLM of the hippocampus exhibited a robust 20-30% increase in vascular density and was accompanied by an increase in expression of inhibitor of differentiation-3. There was also an induction of the angiogenesis markers alphaVbeta3 integrin and Del1. Increases in the vascular density of the SLM could be in response to enhanced metabolic activity in this region. This is supported by the induction of glutamine synthetase and the glutamate transporter GLT1.

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    • "However, increased angiogenesis (and neurogenesis) was observed in SSRI-treated patients suffering from major depression [74]. Similarly, experimental ECS treatment was reported to promote the elongation of existing vessels and to increase their density in the stratum lacunosum moleculare (SLM), a subregion of the hippocampal molecular layer [76, 77]. However, within the granular layer of the dentate gyrus, that is, in the vicinity of stem and progenitor cell somas, we did not detect an increase of the blood vessel density upon experimental ECS treatments (Figure 5). "
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    ABSTRACT: Speculations on the involvement of hippocampal neurogenesis, a form of neuronal plasticity, in the aetiology of depression and the mode of action of antidepressive therapies, started to arise more than a decade ago. But still, conclusive evidence that adult neurogenesis contributes to antidepressive effects of pharmacological and physical therapies has not been generated yet. This review revisits recent findings on the close relation between the mode(s) of action of electroconvulsive therapy (ECT), a powerful intervention used as second-line treatment of major depression disorders, and the neurogenic response to ECT. Following application of electroconvulsive shocks, intricate interactions between neurogenesis, angiogenesis, and microglia activation, the hypothalamic-pituitary-adrenal axis and the secretion of neurotrophic factors have been documented. Furthermore, considering the fact that neurogenesis strongly diminishes along aging, we investigated the response to electroconvulsive shocks in young as well as in aged cohorts of mice.
    Neural Plasticity 05/2014; 2014(11):723915. DOI:10.1155/2014/723915 · 3.60 Impact Factor
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    • "These studies report that ECS treatment induces a dramatic proliferation in endothelial cells in the DG leading to a 30% increase in the total number of endothelial cells, and this increase in cell number results in a 16% increase in vessel length (Hellsten et al., 2005). Similarly, Newton et al. (2006) demonstrated that ECS treatment increases the expression of various angiogenic factors in the hippocampus and leads to an increase in vascular density. There are, however, important differences between the above-mentioned experiments and our study, which may explain these contrasting findings on vascular changes after antidepressant treatment. "
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    ABSTRACT: Exposure to chronic stress alters the number and morphology of neurons and glia in the hippocampal formation; however, little is known about possible changes in vasculature. Here, we examined the effect of chronic social defeat stress on hippocampal vascular supply in rats. Recent reports document that antidepressant treatment can influence angiogenesis in the hippocampus; therefore, we also studied the effect of antidepressant drug treatment on hippocampal capillarization. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) treatment during the last 4 weeks. Rat endothelial cell antigen-1 (RECA-1)-labeling of capillaries and quantitative stereological techniques were used to evaluate the treatment effects on capillary number. Special attention was paid to analysis of the vascular supply of the subgranular zone, which is regarded as an important component of the neurogenic niche for adult hippocampal neurogenesis. Chronic stress significantly decreased the number of microvessels by 30% in all hippocampal subregions, whereas fluoxetine treatment had no influence on capillary number. Furthermore, chronic stress decreased the capillarization of the subgranular zone to a similar extent, indicating that chronic stress affects the vascular niche for adult hippocampal neurogenesis. However, fluoxetine treatment had no impact on capillarization in the subgranular zone. We also detected a decrease in hippocampal volume in the animals as a result of stress, which was mildly altered by fluoxetine treatment. These pronounced changes in vascular supply may explain why the hippocampus is more vulnerable to insults when chronic stress precedes or coincides with other harmful conditions. Reduced microvasculature may also contribute to hippocampal volume decrease in stress-related disorders.
    Hippocampus 01/2009; 20(1):174-85. DOI:10.1002/hipo.20599 · 4.30 Impact Factor
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    • "Moreover, enhanced neurogenesis was required for antidepressant effects (Santarelli et al., 2003). A similar effect was observed for electroconvulsive seizure (ECS) treatment, which also has an antidepressant effect (Madsen et al., 2000; Newton et al., 2006). It is of interest that ECS also enhances angiogenesis, which agrees with the previously observed relationship between angiogenesis and neurogenesis in the hippocampus (Palmer et al., 2000). "
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    ABSTRACT: New fundamental results on stem cell biology have been obtained in the past 15 years. These results allow us to reinterpret the functioning of the cerebral tissue in health and disease. Proliferating stem cells have been found in the adult brain, which can be involved in postinjury repair and can replace dead cells under specific conditions. Numerous genomic mechanisms controlling stem cell proliferation and differentiation have been identified. The involvement of stem cells in the genesis of malignant tumors has been demonstrated. Neural stem cell tropism toward tumors has been shown. These findings suggest new lines of research on brain functioning and development. Stem cells can be used to develop radically new treatments of neurodegenerative and cancer diseases of the brain.
    International Review of Cytology 02/2008; 265:55-109. DOI:10.1016/S0074-7696(07)65002-5 · 9.00 Impact Factor
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