Optical inhibition of striatal neurons promotes focal neurogenesis and neurobehavioral recovery in mice after middle cerebral artery occlusion
Optical inhibition of striatal neurons promotes focal neurogenesis and neurobehavioral recovery in mice after middle cerebral artery occlusion
复制标题
纹状体神经元的光学抑制促进大脑中动脉闭塞后小鼠的局灶性神经发生和神经行为恢复
DOI:
10.1177/0271678x16642242
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发表时间:
2017-03-01
影响因子:
6.3
通讯作者:
Yang, Guo-Yuan
中科院分区:
文献类型:
--
作者:
He, Xiaosong;Lu, Yifan;Yang, Guo-Yuan
Striatal neurons regulate the activity of neural progenitor cells in the subventricular zone, but the effect of striatal neuronal activity on neurogenesis after ischemic stroke is unclear. In this study, we used optogenetic tools to investigate the impact of striatal neuronal activity on the neurogenesis and functional recovery after cerebral ischemia. We transfected striatal neurons with channelrhodopsin-2 or halorhodopsin from Natronomonas so that they can be excited by 473 nm laser or inhibited by 594 nm laser, respectively. Neural inhibition but not excitation at 4–7 days after middle cerebral artery occlusion resulted in reduced atrophy volume (6.8 ± 0.7 vs 8.5 ± 1.2 mm3, p < 0.05) and better performance represented by longer sustaining time on rotarod (99.3 ± 9 vs 80.1 ± 11 s, p < 0.01) and faster moving speed (7.7 ± 2 vs 5.7 ± 1.1 cm/s, p < 0.05) in open field tests. Furthermore, neural inhibition increased the number of nestin+, BrdU+/doublecortin+ and BrdU+/NeuN+ cells (p < 0.001) in the subventricular zone and peri-focal region, and the expression level of axon guidance factor Netrin-1 (0.39 ± 0.16 vs 0.16 ± 0.02, p < 0.05) in the peri-focal region. These data suggest that striatal neuronal activity plays an important role in regulating neurogenesis and neural-behavioral outcomes, and that inhibiting striatal neurons by optogenetics promotes the recovery after ischemic stroke in mice.