Microglia and their CX3CR1 signaling are involved in hippocampal- but not olfactory bulb-related memory and neurogenesis
Microglia and their CX3CR1 signaling are involved in hippocampal- but not olfactory bulb-related memory and neurogenesis
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DOI：
10.1016/j.bbi.2014.04.009
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发表时间：
2014-10-01
影响因子：
15.1
通讯作者：
Yirmiya, Raz
中科院分区：
文献类型：
--
作者：
Reshef, Ronen;Kreisel, Tirzah;Yirmiya, Raz
最近的研究表明，小胶质细胞在认知和神经可塑性过程中发挥重要作用，至少部分通过小胶质细胞CX 3C受体1（CX 3CR 1）信号。此外，小胶质细胞对环境富集（EE）有反应，环境富集调节学习、记忆和神经发生。在本研究中，我们研究了小胶质细胞CX 3CR 1信号传导在CX 3CR 1启动子下的小胶质细胞特异性GFP转基因表达纯合小鼠（CX 3CR 1（-/-）小鼠）中海马和嗅球（OB）相关记忆和神经发生中的作用，其中CX 3CR 1基因功能缺失，以及杂合CX 3CR 1（+/-）和WT对照。我们报道CX 3CR 1缺陷小鼠表现出更好的海马依赖性记忆功能和嗅觉识别，沿着海马小胶质细胞数量和索马大小的增加，提示轻度激活状态，但OB小胶质细胞没有变化。使用CX 3CR 1阻断抗体长期（2周）i. c. v.给药，通过CX 3CR 1信号传导的药理学抑制也诱导了海马依赖性记忆功能和小胶质细胞数量的类似增加。在对照组小鼠中，EE改善了海马依赖性记忆和神经发生，增加了海马小胶质细胞数量和索马体大小，而气味富集（OE）改善了嗅觉识别和OB神经发生，而不改变OB小胶质细胞的状态。在CX 3CR 1缺陷小鼠中，EE和OE没有产生任何进一步的改善记忆功能或神经发生，对小胶质细胞状态没有影响。这些结果支持的概念，在海马小胶质细胞和它们的相互作用与神经元通过CX 3CR 1在记忆功能和神经发生中发挥重要作用，而在OB小胶质细胞似乎不参与这些过程。(C)2014爱思唯尔公司All rights reserved.
Recent studies demonstrate that microglia play an important role in cognitive and neuroplasticity processes, at least partly via microglial CX3C receptor 1 (CX3CR1) signaling. Furthermore, microglia are responsive to environmental enrichment (EE), which modulates learning, memory and neurogenesis. In the present study we examined the role of microglial CX3CR1 signaling in hippocampal- and olfactory-bulb (OB)-related memory and neurogenesis in homozygous mice with microglia-specific transgenic expression of GFP under the CX3CR1 promoter (CX3CR1(-/-) mice), in which the CX3CR1 gene is functionally deleted, as well as heterozygous CX3CR1(+/-) and WT controls. We report that the CX3CR1-deficient mice displayed better hippocampal-dependent memory functioning and olfactory recognition, along with increased number and soma size of hippocampal microglia, suggestive of mild activation status, but no changes in OB microglia. A similar increase in hippocampal-dependent memory functioning and microglia number was also induced by pharmacological inhibition of CX3CR1 signaling, using chronic (2 weeks) i.c.v. administration of CX3CR1 blocking antibody. In control mice, EE improved hippocampal-dependent memory and neurogenesis, and increased hippocampal microglia number and soma size, whereas odor enrichment (OE) improved olfactory recognition and OB neurogenesis without changing OB microglia status. In CX3CR1-deficient mice, EE and OE did not produce any further improvement in memory functioning or neurogenesis and had no effect on microglial status. These results support the notion that in the hippocampus microglia and their interactions with neurons via the CX3CR1 play an important role in memory functioning and neurogenesis, whereas in the OB microglia do not seem to be involved in these processes. (C) 2014 Elsevier Inc. All rights reserved.