Neuronal PTEN deletion in adult cortical neurons triggers progressive growth of cell bodies, dendrites, and axons.
Neuronal PTEN deletion in adult cortical neurons triggers progressive growth of cell bodies, dendrites, and axons.
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DOI：
10.1016/j.expneurol.2018.01.005
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发表时间：
2018-05
影响因子：
5.3
通讯作者：
Steward O
中科院分区：
文献类型：
--
作者：
Gallent EA;Steward O
新生小鼠磷酸酶和张力蛋白（PTEN）基因缺失导致成年后皮质运动神经元（CMNs）胞体增大。在这里，我们评估了成年小鼠中的PTEN缺失是否会引发成熟神经元的生长。通过将AAV-Cre注射到成年转基因小鼠的感觉运动皮层中来缺失PTEN，所述成年转基因小鼠具有PTEN基因的lox-P侧翼外显子5和Cre依赖性报告基因tdTomato。通过tdT表达和荧光金（FG）逆行标记鉴定的PTEN缺失的CMN在PTEN缺失后4个月显著增大，并且在检查的最后时间间隔（缺失后12-15个月）内尺寸继续增加。Sholl的tdT阳性锥体神经元分析显示，在6个月后，成年人的PTEN基因删除的树突状分支的增加，并在12个月更大的增加。成年人PTEN缺失后12个月，髓质锥体中的轴突明显更大，G-比率更高。具有PTEN缺失的小鼠没有表现出明显的神经症状，也没有癫痫发作。在Rotorod和圆柱体测试上对运动功能的评估显示，单侧缺失的协调性轻微受损;然而，在缺失后8个月和10个月，在运动皮层中具有双侧PTEN缺失的小鼠在Rotarod上的表现优于对照组。我们的研究结果表明，强大的神经元生长可以诱导完全成熟的皮层神经元后很长一段时间的发育期已经结束，这种连续的增长发生没有明显的功能障碍。
Deletion of the phosphatase and tensin (PTEN) gene in neonatal mice leads to enlargement of the cell bodies of cortical motoneurons (CMNs) in adulthood. Here, we assessed whether PTEN deletion in adult mice would trigger growth of mature neurons. PTEN was deleted by injecting AAV-Cre into the sensorimotor cortex of adult transgenic mice with a lox-P flanked exon 5 of the PTEN gene and Cre-dependent reporter gene tdTomato. PTEN-deleted CMN’s identified by tdT expression and retrograde labeling with fluorogold (FG) were significantly enlarged four months following PTEN deletion, and continued to increase in size through the latest time intervals examined (12–15 months post-deletion). Sholl analyses of tdT-positive pyramidal neurons revealed increases in dendritic branches at 6 months following adult PTEN deletion, and greater increases at 12 months. 12 months after adult PTEN deletion, axons in the medullary pyramids were significantly larger and G-ratios were higher. Mice with PTEN deletion exhibited no overt neurological symptoms and no seizures. Assessment of motor function on the Rotorod and cylinder test revealed slight impairment of coordination with unilateral deletion; however, mice with bilateral PTEN deletion in the motor cortex performed better than controls on the rotarod at 8 and 10 months post-deletion. Our findings demonstrate that robust neuronal growth can be induced in fully mature cortical neurons long after the developmental period has ended and that this continuous growth occurs without obvious functional impairments.
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DOI：
10.1097/00005072-198909000-00007
发表时间：
1989-09-01
影响因子：
3.2
作者：
MCBRIDE, RL;FERINGA, ER;WILLIAMS, JK
通讯作者：
WILLIAMS, JK
DOI：
10.1073/pnas.1222803110
发表时间：
2013-03-19
影响因子：
11.1
作者：
Takeuchi, Koichi;Gertner, Michael J.;Zukin, R. Suzanne
通讯作者：
Zukin, R. Suzanne
影响因子：
4.2
作者：
Bartlett, JS;Samulski, RJ;McCown, TJ
通讯作者：
McCown, TJ
影响因子：
5.3
作者：
Williams, Michael R.;DeSpenza, Tyrone, Jr.;Luikart, Bryan W.
通讯作者：
Luikart, Bryan W.
影响因子：
5.5
作者：
Sperow, Margaret;Berry, Raymond B.;Zakharenko, Stanislav S.
通讯作者：
Zakharenko, Stanislav S.