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Reduced ccl11/eotaxin mediates the beneficial effects of environmental stimulation on the aged hippocampus
Brain, Behavior, and Immunity ( IF 8.8 ) Pub Date : 2021-08-19 , DOI: 10.1016/j.bbi.2021.08.222
Gaia Scabia 1 , Giovanna Testa 2 , Manuela Scali 3 , Serena Del Turco 4 , Genni Desiato 5 , Nicoletta Berardi 6 , Alessandro Sale 3 , Michela Matteoli 5 , Lamberto Maffei 7 , Margherita Maffei 1 , Marco Mainardi 7 ,
Affiliation  

A deterioration in cognitive performance accompanies brain aging, even in the absence of neurodegenerative pathologies. However, the rate of cognitive decline can be slowed down by enhanced cognitive and sensorimotor stimulation protocols, such as environmental enrichment (EE). Understanding how EE exerts its beneficial effects on the aged brain pathophysiology can help in identifying new therapeutic targets. In this regard, the inflammatory chemokine ccl11/eotaxin-1 is a marker of aging with a strong relevance for neurodegenerative processes. Here, we demonstrate that EE in both elderly humans and aged mice decreases circulating levels of ccl11. Interfering, in mice, with the ccl11 decrease induced by EE ablated the beneficial effects on long-term memory retention, hippocampal neurogenesis, activation of local microglia and of ribosomal protein S6. On the other hand, treatment of standard-reared aged mice with an anti-ccl11 antibody resulted in EE-like improvements in spatial memory, hippocampal neurogenesis, and microglial activation. Taken together, our findings point to a decrease in circulating ccl11 concentration as a key mediator of the enhanced hippocampal function resulting from exposure to EE.



中文翻译:

减少的 ccl11/eotaxin 介导环境刺激对老年海马的有益作用

即使在没有神经退行性疾病的情况下,认知能力的下降也伴随着大脑衰老。然而,认知能力下降的速度可以通过增强认知和感觉运动刺激方案(例如环境富集 (EE))来减缓。了解 EE 如何对老年大脑病理生理学产生有益影响有助于确定新的治疗靶点。在这方面,炎症趋化因子 ccl11/eotaxin-1 是衰老的标志物,与神经退行性过程密切相关。在这里,我们证明了老年人和老年小鼠中的 EE 降低了 ccl11 的循环水平。干扰,在小鼠中,EE 诱导的 ccl11 减少消除了对长期记忆保留、海马神经发生、局部小胶质细胞和核糖体蛋白 S6 的激活。另一方面,用抗 ccl11 抗体治疗标准饲养的老年小鼠导致空间记忆、海马神经发生和小胶质细胞活化方面的 EE 样改善。总之,我们的研究结果表明循环 ccl11 浓度的降低是暴露于 EE 导致海马功能增强的关键介质。

更新日期:2021-08-26
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