Antidepressant-induced vascular dynamics in the hippocampus of adult mouse brain.

Antidepressant-induced vascular dynamics in the hippocampus of adult mouse brain.
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抗抑郁药诱导的成年小鼠大脑海马血管动力学。

DOI:
10.1007/s00441-014-1933-6
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发表时间:
2014
影响因子:
3.6
通讯作者:
S
S
中科院分区:
生物学3区
文献类型:
--
作者:
Mannari;T;Sawa;H;Furube;E;Fukushima;S;Nishikawa;K;Nakashima;T;Miyata;S

文献摘要

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新的神经元不断添加到海马回路中,参与整个生命的空间学习和记忆。这些新的神经元来源于齿状回(DG)颗粒下区(SGZ)的神经干/祖细胞(NSPCs)。最近的研究表明血管重建与神经发生密切相关,但对其机制知之甚少。我们已经研究了成年小鼠脑海马血管重建后,抗抑郁药氟西汀,海马神经发生的有效诱导剂管理。层粘连蛋白和CD 31免疫组化显示,内皮细胞的丝状伪足从已有的粗微血管上长出,并常在两条粗微血管之间形成桥接。这些丝状伪足常见于DG的分子层和齿状门,CA 1的腔隙分子层和CA 3的起始层。丝状伪足仅定位于星形胶质细胞的细胞突起沿着,但与NSPCs的细胞体和突起没有这种密切的联系。氟西汀可使微血管管腔扩大,并可消除分子层和齿状门区内皮细胞的丝状伪足,从而显著增加血管密度。氟西汀治疗增加了颗粒细胞层和齿状门中增殖的NSPCs的数量,以及颗粒细胞层中内皮细胞的数量。因此,抗抑郁药诱导的DG血管动力学可能是由于微血管的管腔大小的改变,而不是内皮细胞的增殖。
New neurons are continuously added to hippocampal circuitry involved with spatial learning and memory throughout life. These new neurons originate from neural stem/progenitor cells (NSPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG). Recent studies indicate that vascular reconstruction is closely connected with neurogenesis, but little is known about its mechanism. We have examined vascular reconstruction in the hippocampus of adult mouse brain after the administration of the antidepressant fluoxetine, a potent inducer of hippocampal neurogenesis. The immunohistochemistry of laminin and CD31 showed that filopodia of endothelial cells sprouted from existing thick microvessels and often formed a bridge between two thick microvessels. These filopodia were frequently seen at the molecular layer and dentate hilus of the DG, the stratum lacunosum-moleculare of the CA1, and the stratum oriens of the CA3. The filopodia were exclusively localized along cellular processes of astrocytes, but such intimate association was not seen with cell bodies and processes of NSPCs. The administration of fluoxetine significantly increased vascular density by enlarging the luminal size of microvessels and eliminating the filopodia of endothelial cells in the molecular layer and dentate hilus. Treatment with fluoxetine increased the number of proliferating NSPCs in the granule cell layer and dentate hilus, and that of endothelial cells in the granule cell layer. Thus, antidepressant-induced vascular dynamics in the DG are possibly attributable to the alteration of the luminal size of microvessels rather than to proliferation of endothelial cells.