Stimulation-dependent remodeling of the corticospinal tract requires reactivation of growth-promoting developmental signaling pathways.
Stimulation-dependent remodeling of the corticospinal tract requires reactivation of growth-promoting developmental signaling pathways.
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DOI：
10.1016/j.expneurol.2018.05.004
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发表时间：
2018-09
影响因子：
5.3
通讯作者：
Martin JH
中科院分区：
文献类型：
--
作者：
Zareen N;Dodson S;Armada K;Awad R;Sultana N;Hara E;Alexander H;Martin JH
The corticospinal tract (CST) can become damaged after spinal cord injury or stroke, resulting in weakness or paralysis. Repair of the damaged CST is limited because mature CST axons fail to regenerate, which is partly because the intrinsic axon growth capacity is downregulated in maturity. Whereas CST axons sprout after injury, this is insufficient to recover lost functions. Chronic motor cortex (MCX) electrical stimulation is a neuromodulatory strategy to promote CST axon sprouting, leading to functional recovery after CST lesion. Here we examine the molecular mechanisms of stimulation-dependent CST axonal sprouting and synapse formation. MCX stimulation rapidly upregulates mTOR and Jak/Stat signaling in the corticospinal system. Chronic stimulation, which leads to CST sprouting and increased CST presynaptic sites, further enhances mTOR and Jak/Stat activity. Importantly, chronic stimulation shifts the equilibrium of the mTOR repressor PTEN to the inactive phosphorylated form suggesting a molecular transition to an axon growth state. We blocked each signaling pathway selectively to determine potential differential contributions to axonal outgrowth and synapse formation. mTOR blockade prevented stimulation-dependent axon sprouting. Surprisingly, Jak/Stat blockade did not abrogate sprouting, but instead prevented the increase in CST presynaptic sites produced by chronic MCX stimulation. Chronic stimulation increased the number of spinal neurons expressing the neural activity marker cFos. Jak/Stat blockade prevented the increase in cFos-expressing neurons after chronic stimulation, confirming an important role for Jak/Stat signaling in activity-dependent CST synapse formation. MCX stimulation is a neuromodulatory repair strategy that reactivates distinct developmentally-regulated signaling pathways for axonal outgrowth and synapse formation.
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影响因子：
82.9
作者：
Eriksson, PS;Perfilieva, E;Gage, FH
通讯作者：
Gage, FH
影响因子：
3.5
作者：
Carmel JB;Martin JH
通讯作者：
Martin JH
影响因子：
5.3
作者：
Brus-Ramer, Marcel;Carmel, Jason B.;Martin, John H.
通讯作者：
Martin, John H.
影响因子：
2.5
作者：
Alvarez, FJ;Villalba, RM;Schneider, SP
通讯作者：
Schneider, SP
DOI：
10.1523/jneurosci.4907-12.2013
发表时间：
2013-03-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Briz V;Hsu YT;Li Y;Lee E;Bi X;Baudry M
通讯作者：
Baudry M