Targeting PTEN but not SOCS3 resists an age-dependent decline in promoting axon sprouting.
Targeting PTEN but not SOCS3 resists an age-dependent decline in promoting axon sprouting.
复制标题
靶向PTEN，但不是SOCS3，可以抵抗促进轴突发芽的年龄依赖性下降。
DOI：
10.1016/j.isci.2022.105383
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发表时间：
2022-11-18
期刊：
影响因子：
5.8
通讯作者：
Zheng, Binhai
中科院分区：
文献类型：
--
作者：
Geoffroy, Cedric G.;Meves, Jessica M.;Kim, Hugo Jae Mun;Romaus-Sanjurjo, Daniel;Sutherland, Theresa C.;Li, Jeffrey J.;Suen, Juliet;Sanchez, Joshua J.;Zheng, Binhai
轴突修复对于CNS损伤后的功能恢复至关重要。我们以前报道过，神经元PTEN缺失表现出年龄依赖性的下降，促进轴突再生从皮质脊髓束（CST）。未受伤轴突的发芽，一种自然发生的轴突修复形式，如何受到年龄的影响尚不清楚。我们在不同年龄的PTEN和/或SOCS 3缺失小鼠中评估了单侧延髓切开术后的CST发芽。虽然PTEN缺失增强发芽独立于年龄，SOCS 3缺失失去其发芽促进作用与年龄。随着年龄的增长，PTEN/SOCS 3共缺失对CST发芽的协同作用迅速丧失。总的来说，促进发芽在年龄上比再生更稳健，但不同的分子途径受到年龄的不同影响。重要的是，延迟6周的PTEN缺失促进了CST在各年龄组中的发芽，支持了这种神经修复策略的临床相关时间框架，与年龄无关。神经元PTEN缺失促进中年小鼠中稳健的CST轴突发芽SOCS 3缺失失去促进中年小鼠中轴突发芽的有效性PTEN和SOCS 3共缺失随着年龄的增加迅速失去协同作用成年小鼠中延迟的PTEN缺失促进跨年龄组的CST轴突发芽分子神经科学;细胞神经科学
Axonal repair is critical for functional recovery after injury of the CNS. We previously reported that neuronal PTEN deletion exhibits an age-dependent decline in promoting axon regeneration from the corticospinal tract (CST). How sprouting of uninjured axons, a naturally occurring form of axonal repair, is impacted by age is unknown. We assessed CST sprouting after unilateral pyramidotomy in PTEN and/or SOCS3-deleted mice at different ages. While PTEN deletion enhances sprouting independently of age, SOCS3 deletion loses its sprouting-promoting effect with age. The synergistic effect of PTEN/SOCS3 co-deletion on CST sprouting is rapidly lost with increased age. Overall, promoting sprouting appears more robust across age than regeneration, yet distinct molecular pathways are differentially impacted by age. Importantly, six-week delayed PTEN deletion promotes CST sprouting across age groups, supporting a clinically relevant time frame for this neural repair strategy independently of age. Neuronal PTEN deletion promotes robust CST axon sprouting in middle-aged mice SOCS3 deletion loses effectiveness in promoting axon sprouting in middle-aged mice PTEN and SOCS3 co-deletion rapidly loses synergy with increased age Delayed PTEN deletion in adult mice promotes CST axon sprouting across age groups Molecular neuroscience; Cellular neuroscience
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影响因子：
16.2
作者：
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影响因子：
25
作者：
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