ICV ADMINISTRATION OF OREXIN-A INDUCES AN ANTIDEPRESSIVE-LIKE EFFECT THROUGH HIPPOCAMPAL CELL PROLIFERATION
ICV ADMINISTRATION OF OREXIN-A INDUCES AN ANTIDEPRESSIVE-LIKE EFFECT THROUGH HIPPOCAMPAL CELL PROLIFERATION
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DOI：
10.1016/j.neuroscience.2008.09.042
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发表时间：
2008-12-10
期刊：
影响因子：
3.3
通讯作者：
Hanawa, T.
中科院分区：
文献类型：
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作者：
Ito, N.;Yabe, T.;Hanawa, T.
据报道，食欲素-A（OX-A）水平的降低与抑郁症有关。众所周知，压力和抑郁可以破坏海马齿状回的神经发生;然而，还不清楚OX-A如何参与抑郁和/或神经发生。在本研究中，我们研究了静脉注射OX-A对强迫游泳试验（FST）的影响，这是一种公认的抗抑郁样活性的行为筛选，并在静脉注射OX-A后4天用溴脱氧尿苷（BrdU）在齿状回中观察细胞增殖。OX-A给药（140 pmol/小鼠）导致FST中动物不动性显著降低，而不影响自发运动活动或血清皮质酮水平。此外，在OX-A处理的小鼠体内齿状回中BrdU阳性细胞的数量显著增加;然而，OX-A并不影响齿状回中doublecortin阳性细胞的百分比。OX-A处理对大鼠胎脑神经前体细胞的增殖无明显影响，且这些细胞中不表达OXR 1蛋白。用0XR 1拮抗剂SB-334867（30 mg/kg，i. p.）阻断OX-A诱导的FST不动性的降低和BrdU阳性的增加。此外，SB-334867阻断了OX-A诱导的齿状回门神经肽Y（NPY）阳性细胞的增加。这些结果表明，OX-A诱导抗抑郁样作用，至少部分，通过增强齿状回细胞增殖。OX-A的这些作用可能与其对齿状回门区NPY系统的调节有关。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
A decrease in orexin-A (OX-A) levels has been reported to be associated with depression. It is also well known that stress and depression can disrupt neurogenesis in the dentate gyrus of the hippocampus; however, it is unclear how OX-A is involved in depression and/or neurogenesis. In the present study, we investigated the effect of i.c.v. administration of OX-A on the forced swimming test (FST), an accepted behavioral screen of antidepressant-like activity, and on the cell proliferation with bromodeoxyuridine (BrdU) in the dentate gyrus at 4 days after i.c.v. administration of OX-A. OX-A administration (140 pmol/mouse) led to a significant reduction in animal immobility in the FST, without affecting spontaneous locomotor activities or serum corticosterone levels. In addition, the number of BrdU-positive cells in the dentate gyrus was significantly increased in OX-A-treated mice in vivo; however, OX-A did not affect the percentage of doublecortin-positive cells in the dentate gyrus. The proliferation of neural progenitor cells derived from rat fetal brain was not affected by OX-A treatment in vitro, and the orexin receptor 1 (OXR1) protein was not expressed in these cells. Treatment with the OXR1 antagonist SB-334867 (30 mg/kg, i.p.) blocked both the OX-A-induced decrease in the immobility of FST and increase in BrdU-positive. Moreover, the OX-A-induced increase in neuropeptide Y (NPY)positive cells in the hilus of the dentate gyrus was blocked by SB-334867. These results suggest that OX-A induces an antidepressive-like effect, at least in part, via the enhancement of cell proliferation in the dentate gyrus. These effects of OX-A also may be partly relevant to the regulation of the NPY system in the hilus of the dentate gyrus. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.