Motoneuron activity is required for enhancements in functional recovery after peripheral nerve injury in exercised female mice.
Motoneuron activity is required for enhancements in functional recovery after peripheral nerve injury in exercised female mice.
复制标题
DOI：
10.1002/jnr.24109
复制
发表时间：
2020-03
影响因子：
4.2
通讯作者：
English AW
中科院分区：
文献类型：
--
作者：
Jaiswal PB;Tung JK;Gross RE;English AW
抑制性发光蛋白（iLMO 2）整合了光遗传学和化学遗传学方法，并允许对神经元活性进行细胞类型特异性抑制。当暴露于海肾荧光素酶底物腔肠素（CTZ）时，iLMO 2产生生物发光介导的其氨基末端盐视紫红质活化，导致神经元抑制。在外周神经损伤后，以间歇性跑步机训练（IT）的形式进行适度的日常锻炼，可增强雌性小鼠的运动轴突再生和肌纤维神经再支配。我们假设，iLMO 2介导的运动神经元活动的抑制在IT将阻止这种增强。向年轻雌性ChAT-IRES-Cre小鼠的腓肠肌和胫骨前肌中单侧肌内注射Cre依赖性AAV 2/9-EF 1a-DIO-iLMO 2（~8.5×1013 vg/ml），从而特异性限制iLMO 2表达至其运动神经元。允许进行4至6周的逆行病毒转导，之后进行单侧坐骨神经横断（Tx）和修复。将动物随机分为四组：仅IT组、IT+CTZ组、仅CTZ组和未处理组（UT）。Tx修复后三周，仅IT组中两块肌肉的最大幅度直接肌肉反应（M-max）显著大于UT小鼠，与该运动方案的增强效果一致。在运动前30分钟注射CTZ，抑制运动过程中运动神经元的活动，完全阻断了运动的增强作用。在没有iLMO 2的小鼠中使用CTZ进行类似处理对再生没有影响。神经元活动是运动成功促进运动轴突再生所必需的。
Inhibitory luminopsins (iLMO2) integrate opto- and chemo-genetic approaches and allow for cell-type specific inhibition of neuronal activity. When exposed to a Renilla luciferase substrate, Coelenterazine (CTZ), iLMO2 generates bioluminescence-mediated activation of its amino-terminal halorhodopsin, resulting in neuronal inhibition. Moderate daily exercise in the form of interval treadmill-training (IT) applied following a peripheral nerve injury results in enhanced motor axon regeneration and muscle fiber reinnervation in female mice. We hypothesized that iLMO2 mediated inhibition of motoneuron activity during IT would block this enhancement. Unilateral intramuscular injections of Cre-dependent AAV2/9-EF1a-DIO-iLMO2 (~8.5×1013 vg/ml) were made into the gastrocnemius and tibialis anterior muscles of young female ChAT-IRES-Cre mice, thereby limiting iLMO2 expression specifically to their motoneurons. Four to six weeks were allowed for retrograde viral transduction after which a unilateral sciatic nerve transection (Tx) and repair was performed. Animals were randomized into four groups: IT only, IT+CTZ, CTZ only, and untreated (UT). Three weeks post Tx-repair, the maximal amplitude direct muscle responses (M-max) in both muscles in the IT only group were significantly greater than in UT mice, consistent with the enhancing effects of this exercise regimen. Inhibiting motoneuron activity during exercise by a single injection of CTZ, administered 30 minutes prior to exercise, completely blocked the enhancing effect of exercise. Similar treatments with CTZ in mice without iLMO2 had no effect on regeneration. Neuronal activity is required for successful enhancement of motor axon regeneration by exercise.
登录
查看更多内容
影响因子：
2.2
作者：
English, Arthur W.;Wilhelm, Jennifer C.;Sabatier, Manning J.
通讯作者：
Sabatier, Manning J.
通过GFP-LAC阻遏物标记，荧光原位杂交和免疫染色来对DNA检测进行定量比较。
影响因子：
3.5
作者：
通讯作者：
--
影响因子：
2.5
作者：
Boeltz, Tiffany;Ireland, Meredith;English, Arthur W.
通讯作者：
English, Arthur W.
影响因子：
3.3
作者：
Lerman, I;Harrison, BC;Leinwand, LA
通讯作者：
Leinwand, LA
影响因子：
3.3
作者：
Lundbye-Jensen, Jesper;Nielsen, Jens Bo
通讯作者：
Nielsen, Jens Bo