GHRELIN ADMINISTRATION ENHANCES NEUROGENESIS BUT IMPAIRS SPATIAL LEARNING AND MEMORY IN ADULT MICE

GHRELIN ADMINISTRATION ENHANCES NEUROGENESIS BUT IMPAIRS SPATIAL LEARNING AND MEMORY IN ADULT MICE
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施用生长素释放肽可增强成年小鼠的神经发生,但会损害空间学习和记忆

DOI:
10.1016/j.neuroscience.2013.10.063
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发表时间:
2014
期刊:
影响因子:
3.3
通讯作者:
Zhou Y.
Zhou Y.
中科院分区:
医学3区
文献类型:
--
作者:
Zhao Z.;Liu H.;Xiao K.;Yu M.;Cui L.;Zhu Q.;Zhao R.;Li G-D.;Zhou Y.

文献摘要

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据报道,胃饥饿素是一种促进人类和啮齿动物摄食和调节能量代谢的促氧脑-肠激素,可以促进成人神经发生和海马依赖性记忆的形成。然而,胃饥饿素诱导的海马神经发生是否与记忆改善有关尚不清楚。利用5-溴-2 '脱氧尿素(BrdU)对出生日期新生神经元和c-Fos的表达来鉴定参与记忆过程的齿状回(DG)神经元,我们在这里检查了ghrelin治疗对小鼠成年神经发生和认知行为的影响。我们进一步研究了生长素对完整小鼠空间记忆痕迹中新神经元募集的可能影响。我们发现,全身胃饥饿素治疗(80 μg/kg,每天1次,连续8天)刺激了成年海马的神经发生,但对空间记忆的形成没有影响。与此一致的是,它并不影响新生神经元融入空间记忆回路。相反,在海马CA1区局部注射ghrelin (8 ng/0.5 μl)会损害空间记忆的形成,但对成体神经发生没有影响。因此,我们的研究结果表明,胃饥饿素在调节成人神经发生和海马记忆习得过程中发挥着不同的作用,这两个过程可能并不相关,可能通过不同的机制介导。
Ghrelin, an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents, was reported to enhance both adult neurogenesis and hippocampus-dependent memory formation. However, it is still unclear whether ghrelin-induced hippocampus neurogenesis is responsible for its memory improvement. Using 5-bromo-2′ deoxyuridien (BrdU) to birth-date newborn neurons and c-Fos expression to identify dentate gyrus (DG) neurons involved in memory processes, we checked here the effect of ghrelin treatment on adult neurogenesis and cognitive behaviors in mice. We further examined the possible effect of ghrelin on the recruitment of new neurons into the spatial memory traces in intact mice. We found that systemic ghrelin treatment (80 μg/kg, ip injection once daily for 8 days) stimulated neurogenesis in the adult hippocampus, but had no effect on spatial memory formation. Consistently, it did not affect the incorporation of newborn neurons into the spatial memory circuits. On the contrary, local infusion of ghrelin (8 ng/0.5 μl into CA1 region of the hippocampus) impaired spatial memory formation, but did not affect adult neurogenesis. Our results thus suggested that ghrelin plays distinct roles in modulating adult neurogenesis and the memory acquisition in the hippocampus, the two processes may not be correlated and may be mediated by different mechanisms.