Loss of the mu opioid receptor on different genetic backgrounds leads to increased bromodeoxyuridine labeling in the dentate gyrus only after repeated injection.

Loss of the mu opioid receptor on different genetic backgrounds leads to increased bromodeoxyuridine labeling in the dentate gyrus only after repeated injection.
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DOI:
10.1016/j.neuroscience.2011.12.046
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发表时间:
2012-03-29
期刊:
影响因子:
3.3
通讯作者:
Pintar, J. E.
Pintar, J. E.
中科院分区:
医学3区
文献类型:
--
作者:
Cominski, T. P.;Turchin, C. E.;Hsu, M. S.;Ansonoff, M. A.;Pintar, J. E.

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内源性阿片系统参与多种生理过程,包括海马齿状回的神经发生。在目前的研究中,我们研究了Mu阿片受体(Mor-1)在DG神经发生中的作用,并在几种注射模式下测定了糖皮质激素水平,以补充神经发生实验。对C57BL/6和129S6背景的MOR-1基因敲除(KO)小鼠分别采用单次注射和两种不同的重复注射方案注射BrdU,然后在不同的时间点处死。重复注射后,MOR-1KO小鼠DG中BrdU和增殖细胞核抗原阳性细胞总数较WT小鼠显著增加,但单次注射后无明显变化。单次注射和重复注射后,MOR-1 KO和WT小鼠的血浆皮质酮(CORT)水平均有类似的升高,表明应激反应在任何注射方案下都会被激活,但导致MOR-1 KO小鼠BrdU标记增加的机制与皮质酮水平无关。最后,与基因无关的WT 129S6小鼠在未注射对照组和注射后两个时间点的血浆CORT水平均高于WT C57BL/6小鼠;这些水平与129S6小鼠DG中BrdU细胞数量低于C57BL/6小鼠呈负相关。综上所述,这些数据表明,MOR-1的丢失增加了DG中BrdU的标记,与皮质醇水平无关,但只有在重复注射后才会增加,这说明了注射范例以一种依赖于基因的方式影响细胞增殖反应的能力。
The endogenous opioid system is involved in various physiological processes including neurogenesis in the dentate gyrus (DG) of the hippocampus. In the current study, we investigated the role of the mu opioid receptor (MOR-1) on DG neurogenesis and measured glucocorticoid levels following several injection paradigms to supplement the neurogenesis experiments. MOR-1 knockout (KO) mice on C57BL/6 and 129S6 backgrounds were injected with BrdU using either a single injection or two different repeated injection protocols and then sacrificed at different time points. The total number of BrdU and PCNA positive cells in the DG is significantly increased in MOR-1 KO mice compared to WT on both strains after repeated injection, but not after a single injection. Plasma corticosterone (CORT) levels increased similarly in MOR-1 KO and WT mice following both single and repeated injection, indicating that the stress response is activated following any injection protocol, but that the mechanism responsible for the increase in BrdU labeling in MOR-1 KO mice is CORT-level independent. Finally, WT 129S6 mice, independent of genotype, showed higher levels of plasma CORT compared to WT C57BL/6 mice in both non-injected controls and following injection at two separate time points; these levels were inversely correlated with low numbers of BrdU cells in the DG in 129S6 mice compared to C57BL/6 mice. In summary, these data demonstrate that loss of MOR-1 increases BrdU labeling in the DG independent of CORT levels, but only following a repeated injection, illustrating the capability of injection paradigms to influence cell proliferative responses in a genotype-dependent manner.
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