Restoring Cellular Energetics Promotes Axonal Regeneration and Functional Recovery after Spinal Cord Injury.

Cell Metabolism
Qi HanXiao-Ming Xu

Abstract

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 insights 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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Citations

Oct 6, 2020·Frontiers in Cell and Developmental Biology·Juan Sebastián JaraEdmund R Hollis
Sep 30, 2020·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Xiaoqin HuangLi Chen
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Oct 17, 2020·Neural Regeneration Research·Qi Han, Xiao-Ming Xu
Mar 5, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Chen ZhaoHaifeng Liu
Mar 7, 2021·International Journal of Molecular Sciences·Veselina PetrovaRichard Eva
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Jul 3, 2021·Cells·Vasiliki Tsata, Daniel Wehner
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Aug 8, 2021·International Journal of Molecular Sciences·Miguel E Domínguez-Romero, Paula G Slater
Nov 11, 2020·Journal of Agricultural and Food Chemistry·Jing LiJun-Qing Huang

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