Electroconvulsive seizure increases adult hippocampal angiogenesis in rats

Electroconvulsive seizure increases adult hippocampal angiogenesis in rats
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DOI:
10.1111/j.1460-9568.2006.04958.x
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发表时间:
2006-08-01
影响因子:
3.4
通讯作者:
Duman, Ronald S.
Duman, Ronald S.
中科院分区:
医学3区
文献类型:
--
作者:
Newton, Samuel S.;Girgenti, Matthew J.;Duman, Ronald S.

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电惊厥发作在治疗严重抑郁症和治疗难治性抑郁症方面已被证明具有治疗应用。尽管电惊厥发作作为一种非化学抗抑郁药物治疗有效,但其作用机制尚不清楚。海马营养因子表达的升高和伴随的细胞增殖被认为在其作用中起作用。我们研究了报道的诱导血管生成因子和内皮细胞增殖是否会导致血管密度的增加。采用血管密度定量、血管生成基因表达分析和免疫组织化学相结合的方法检测海马齿状回和腔隙层分子(SLM)两个区域。齿状回血管密度增加6%,但没有统计学意义。海马SLM血管密度显著增加20-30%,并伴有分化抑制剂-3的表达增加。血管生成标记α V β 3整合素和Del1也有诱导作用。SLM血管密度的增加可能是对该区域代谢活动增强的反应。这是由谷氨酰胺合成酶和谷氨酸转运体GLT1的诱导所支持的。
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 alpha V beta 3 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.