Fractalkine and CX 3 CR1 regulate hippocampal neurogenesis in adult and aged rats.
Fractalkine and CX 3 CR1 regulate hippocampal neurogenesis in adult and aged rats.
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DOI：
10.1016/j.neurobiolaging.2009.11.022
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发表时间：
2011-11
影响因子：
4.2
通讯作者：
Gemma, Carmelina
中科院分区：
文献类型：
--
作者：
Bachstetter, Adam D.;Morganti, Josh M.;Jernberg, Jennifer;Schlunk, Andrea;Mitchell, Staten H.;Brewster, Kaelin W.;Hudson, Charles E.;Cole, Michael J.;Harrison, Jeffrey K.;Bickford, Paula C.;Gemma, Carmelina
小胶质细胞具有神经保护能力，但慢性激活可促进神经毒性炎症。神经元fractalkine（FKN），作用于CX 3CR 1，已被证明可以抑制过度的小胶质细胞活化。我们发现，在年轻成年啮齿类动物中，FKN/CX 3CR 1信号传导的中断通过IL-1β降低了神经祖细胞的存活和增殖。老年大鼠海马FKN蛋白水平降低;此外，这些动物中CX 3CR 1功能的中断并不影响神经发生。外源性FKN可逆转海马神经发生的年龄相关性下降，从而恢复FKN的年龄相关性丢失。通过添加外源性FKN，幼龄动物中没有可测量的变化。这些结果表明，FKN/CX 3CR 1信号转导具有调节作用，通过涉及间接修改的生态位环境的机制，在调制海马神经发生。由于神经炎症升高与许多年龄相关的神经退行性疾病相关，因此增强FKN/CX 3CR 1相互作用可以提供一种替代治疗方法来减缓年龄相关的神经退行性疾病。
Microglia have neuroprotective capacities, yet chronic activation can promote neurotoxic inflammation. Neuronal fractalkine (FKN), acting on CX3CR1, has been shown to suppress excessive microglia activation. We found that disruption in FKN/ CX3CR1 signaling in young adult rodents decreased survival and proliferation of neural progenitor cells through IL-1β. Aged rats were found to have decreased levels of hippocampal FKN protein; moreover, interruption of CX3CR1 function in these animals did not affect neurogenesis. The age-related loss of FKN could be restored by exogenous FKN reversing the age-related decrease in hippocampal neurogenesis. There were no measureable changes in young animals by the addition of exogenous FKN. The results suggest that FKN/ CX3CR1 signaling has a regulatory role in modulating hippocampal neurogenesis via mechanisms that involve indirect modification of the niche environment. As elevated neuroinflammation is associated with many age-related neurodegenerative diseases, enhancing FKN/ CX3CR1 interactions could provide an alternative therapeutic approach to slow age-related neurodegeneration.
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影响因子：
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作者：
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