Environmental Enrichment Restores Memory Functioning in Mice with Impaired IL-1 Signaling via Reinstatement of Long-Term Potentiation and Spine Size Enlargement
Environmental Enrichment Restores Memory Functioning in Mice with Impaired IL-1 Signaling via Reinstatement of Long-Term Potentiation and Spine Size Enlargement
复制标题
DOI：
10.1523/jneurosci.5352-08.2009
复制
发表时间：
2009-03-18
影响因子：
5.3
通讯作者：
Yirmiya, Raz
中科院分区：
文献类型：
--
作者：
Goshen, Inbal;Avital, Avi;Yirmiya, Raz
环境丰富（EE）被发现，以促进记忆功能和神经可塑性在正常和神经功能受损的动物。然而，这种操作的能力，以挽救记忆和其生物基质的动物与特定的遗传基础上的缺陷，在这些功能还没有得到广泛的研究。在本研究中，我们研究了EE在两种小鼠模型的记忆功能和可塑性受损的影响。先前的研究表明，细胞因子白细胞介素-1（IL-1 rKO）受体缺失的小鼠和CNS特异性转基因过表达IL-1受体拮抗剂（IL-1 raTG）的小鼠显示海马记忆和长时程增强（LTP）受损。我们在这里报告了EE对IL-1 rKO和IL-1 raTG小鼠空间和背景记忆的纠正作用，并揭示了这种有益作用的两种机制：伴随着他们的记忆功能紊乱，在常规环境中饲养的IL-1 rKO小鼠的LTP受损，树突棘大小减少。这两种损害都被环境富集所纠正。在常规环境中饲养的IL-1 rKO小鼠中，没有发现神经发生或海马BDNF和血管内皮生长因子分泌的缺陷，并且这两个变量在富集的IL-1 rKO和野生型小鼠中增加到相似的程度。这些研究结果表明，暴露于丰富的环境可能是有益的个人与IL-1信号传导的遗传损伤（和可能的其他遗传原因），通过逆转损伤的齿状回LTP和脊柱的大小，并通过促进神经发生和营养因子分泌的学习和记忆受损。
Environmental enrichment (EE) was found to facilitate memory functioning and neural plasticity in normal and neurologically impaired animals. However, the ability of this manipulation to rescue memory and its biological substrate in animals with specific genetically based deficits in these functions has not been extensively studied. In the present study, we investigated the effects of EE in two mouse models of impaired memory functioning and plasticity. Previous research demonstrated that mice with a deletion of the receptor for the cytokine interleukin-1 (IL-1rKO), and mice with CNS-specific transgenic over-expression of the IL-1 receptor antagonist (IL-1raTG) display impaired hippocampal memory and long-term potentiation (LTP). We report here a corrective effect of EE on spatial and contextual memory in IL-1rKO and IL-1raTG mice and reveal two mechanisms for this beneficial effect: Concomitantly with their disturbed memory functioning, LTP in IL-1rKO mice that were raised in a regular environment is impaired, and their dendritic spine size is reduced. Both of these impairments were corrected by environmental enrichment. No deficiencies in neurogenesis or hippocampal BDNF and vascular endothelial growth factor secretion were found in IL-1rKO mice that were raised in a regular environment, and both of these variables were increased to a similar degree in enriched IL-1rKO and wild-type mice. These findings suggest that exposure to an enriched environment may be beneficial for individuals with impaired learning and memory related to genetic impairments of IL-1 signaling (and possibly other genetic causes), by reversing impairments in dentate gyrus LTP and spine size and by promoting neurogenesis and trophic factors secretion.