期刊
NATURE NEUROSCIENCE
卷 13, 期 9, 页码 1075-U64出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2603
关键词
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资金
- Wings for Life
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Craig H. Neilson Foundation
- National Institute of Neurological Disorders and Stroke
- International Spinal Research Trust
Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. We found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons. After development, the regrowth potential of CST axons was lost and this was accompanied by a downregulation of mTOR activity in corticospinal neurons. Axonal injury further diminished neuronal mTOR activity in these neurons. Forced upregulation of mTOR activity in corticospinal neurons by conditional deletion of Pten, a negative regulator of mTOR, enhanced compensatory sprouting of uninjured CST axons and enabled successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possessed the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.
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