Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice.
Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice.
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DOI：
10.1016/j.expneurol.2015.02.012
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发表时间：
2015-04
影响因子：
5.3
通讯作者：
Steward, Oswald
中科院分区：
文献类型：
--
作者：
Danilov, Camelia A.;Steward, Oswald
关键词：
先前的研究表明，新生小鼠中磷酸酶和张力蛋白同源物（PTEN）的条件性基因缺失可增强成人脊髓损伤（SCI）后轴突的再生能力。在这里，我们评估了在 SCI 后删除成年神经元中的 PTEN 是否也有效，以及增强的再生生长是否伴随着自主运动功能的增强恢复。 PTENloxP/loxP 小鼠在颈椎 5 (C5) 处受到中度挫伤。一组接受单侧注射表达 CRE 的腺相关病毒 (AAV-CRE) 至感觉运动皮层；对照组接受表达绿色荧光蛋白（AAV-GFP）的载体或仅接受损伤（无载体注射）。 SCI 后 14 周，使用握力计 (GSM) 和悬挂任务测试前肢功能。通过将微型红宝石 BDA 注射到感觉运动皮层来追踪皮质脊髓束 (CST)。脊髓损伤后，前肢抓握能力立即严重受损，但随着时间的推移缓慢恢复。与 AAV-GFP 组或仅损伤组相比，PTEN 缺失小鼠的恢复程度明显更大。 BDA 束追踪显示，与对照组相比，PTEN 缺失组的尾段中 BDA 标记的轴突数量显着增加。此外，在PTEN缺失组中，有丰富的络脉从主束吻侧延伸到病变部位，进入损伤部位的疤痕组织及其周围。这些结果表明，在 SCI 后不久的成年小鼠中，PTEN 缺失可以增强 CST 轴突的再生生长和前肢运动功能的恢复。
Previous studies indicate that conditional genetic deletion of phosphatase and tensin homolog (PTEN) in neonatal mice enhances the ability of axons to regenerate following spinal cord injury (SCI) in adults. Here, we assessed whether deleting PTEN in adult neurons post-SCI is also effective, and whether enhanced regenerative growth is accompanied by enhanced recovery of voluntary motor function. PTENloxP/loxP mice received moderate contusion injuries at cervical level 5 (C5). One group received unilateral injections of adeno-associated virus expressing CRE (AAV-CRE) into the sensorimotor cortex; controls received a vector expressing green fluorescent protein (AAV-GFP) or injuries only (no vector injections). Forelimb function was tested for 14 weeks post-SCI using a grip strength meter (GSM) and a hanging task. The corticospinal tract (CST) was traced by injecting mini-ruby BDA into the sensorimotor cortex. Forelimb gripping ability was severely impaired immediately post-SCI but recovered slowly over time. The extent of recovery was significantly greater in PTEN-deleted mice in comparison to either the AAV-GFP group or the injury only group. BDA tract tracing revealed significantly higher numbers of BDA-labeled axons in caudal segments in the PTEN-deleted group compared to control groups. In addition, in the PTEN-deleted group, there were exuberant collaterals extending from the main tract rostral to the lesion, into and around the scar tissue at the injury site. These results indicate that PTEN deletion in adult mice shortly post-SCI can enhance regenerative growth of CST axons and forelimb motor function recovery.
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影响因子：
16.2
作者：
Smith, Patrice D.;Sun, Fang;Park, Kevin Kyungsuk;Cai, Bin;Wang, Chen;Kuwako, Kenichiro;Martinez-Carrasco, Irene;Connolly, Lauren;He, Zhigang
通讯作者：
He, Zhigang
全身性PTEN拮抗剂肽对脊髓损伤后轴突生长和功能恢复的影响。
影响因子：
14
作者：
Ohtake, Yosuke;Park, Dongsun;Abdul-Muneer, P. M.;Li, Hui;Xu, Bin;Sharma, Kartavya;Smith, George M.;Selzer, Michael E.;Li, Shuxin
通讯作者：
Li, Shuxin
影响因子：
2.5
作者：
Steward, O;Zheng, BH;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M
影响因子：
2.7
作者：
Kanagal, Srikanth G.;Muir, Gillian D.
通讯作者：
Muir, Gillian D.
影响因子：
5.3
作者：
SCHRIMSHER, GW;REIER, PJ
通讯作者：
REIER, PJ