Journal
CELL METABOLISM
Volume 31, Issue 3, Pages 623-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2020.02.002
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Funding
- NIH, United States [1R01 100531, 1R01 NS103481]
- Merit Review Award from the U.S. Department of Veterans Affairs, United States [I01 BX002356, I01 BX003705, I01 RX002687]
- Indiana Spinal Cord and Brain Injury Research Foundation, United States [19919]
- Mari Hulman George Endowment Funds
- Intramural Research Program of NINDS, NIH, United States [ZIA NS003029, ZIA NS002946]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [ZIANS003029, ZIANS002946] Funding Source: NIH RePORTER
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Axonal regeneration in the central nervous system (CNS) is a highly energy-demanding process. Extrinsic insults and intrinsic restrictions lead to an energy crisis in injured axons, raising the question of whether recovering energy deficits facilitates regeneration. Here, we reveal that enhancing axonal mitochondrial transport by deleting syntaphilin (Snph) recovers injury-induced mitochondrial depolarization. Using three CNS injury mouse models, we demonstrate that Snph(-/-) mice display enhanced corticospinal tract (CST) regeneration passing through a spinal cord lesion, accelerated regrowth of monoaminergic axons across a transection gap, and increased compensatory sprouting of uninjured CST. Notably, regenerated CST axons form functional synapses and promote motor functional recovery. Administration of the bioenergetic compound creatine boosts CST regenerative capacity in Snph(-/-) mice. Our study provides mechanistic in-sights into intrinsic regeneration failure in CNS and suggests that enhancing mitochondrial transport and cellular energetics are promising strategies to promote regeneration and functional restoration after CNS injuries.
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