scholarly journals Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits

2016 ◽  
Vol 214 (1) ◽  
pp. 103-119 ◽  
Author(s):  
Bing Zhou ◽  
Panpan Yu ◽  
Mei-Yao Lin ◽  
Tao Sun ◽  
Yanmin Chen ◽  
...  
Keyword(s):  
Axon Regeneration ◽  
Genetic Manipulation ◽  
Atp Depletion ◽  
Sciatic Nerve Crush ◽  
Nerve Crush ◽  
Mitochondrial Transport ◽  
Anchoring Protein ◽  
Mature Neuron ◽  
Mature Neurons

Although neuronal regeneration is a highly energy-demanding process, axonal mitochondrial transport progressively declines with maturation. Mature neurons typically fail to regenerate after injury, thus raising a fundamental question as to whether mitochondrial transport is necessary to meet enhanced metabolic requirements during regeneration. Here, we reveal that reduced mitochondrial motility and energy deficits in injured axons are intrinsic mechanisms controlling regrowth in mature neurons. Axotomy induces acute mitochondrial depolarization and ATP depletion in injured axons. Thus, mature neuron-associated increases in mitochondria-anchoring protein syntaphilin (SNPH) and decreases in mitochondrial transport cause local energy deficits. Strikingly, enhancing mitochondrial transport via genetic manipulation facilitates regenerative capacity by replenishing healthy mitochondria in injured axons, thereby rescuing energy deficits. An in vivo sciatic nerve crush study further shows that enhanced mitochondrial transport in snph knockout mice accelerates axon regeneration. Understanding deficits in mitochondrial trafficking and energy supply in injured axons of mature neurons benefits development of new strategies to stimulate axon regeneration.

scholarly journals LncRNA BC083743 Promotes the Proliferation of Schwann Cells and Axon Regeneration Through miR-103-3p/BDNF After Sciatic Nerve Crush

2020 ◽  
Vol 79 (10) ◽  
pp. 1100-1114
Author(s):  
Lin Gao ◽  
Aiqin Feng ◽  
Peijian Yue ◽  
Yue Liu ◽  
Qiaoyu Zhou ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cells ◽  
Axon Regeneration ◽  
Underlying Mechanism ◽  
Regulation Mechanism ◽  
Sciatic Nerve Crush ◽  
Bdnf Expression ◽  
Nerve Crush

Abstract To investigate the underlying mechanism of lncRNA BC083743 in regulating the proliferation of Schwann cells (SCs) and axon regeneration after sciatic nerve crush (SNC), we used a rat model. Sciatic function index and the atrophy ratio of gastrocnemius muscle were evaluated. The relationship among BC083743, miR-103-3p, and brain-derived neurotrophic factor (BDNF) and their regulation mechanism in the repair of SNC were investigated using in vivo and in vitro experiments. The expression changes of BC083743 were positively associated with that of BDNF following SNC, but the expression changes of miR-103-3p were inversely associated with that of BDNF. The SC proliferation and BDNF expression could be promoted by overexpression of BC083743, while they were inhibited by a miR-103-3p mimic. In addition, BC083743 interacted with and regulated miR-103-3p, thereby promoting BDNF expression and SC proliferation. BC083743 overexpression also promoted axon regeneration through miR-103-3p. In vivo experiments also indicated that BC083743 overexpression promoted the repair of SNC. In conclusion, LncRNA BC083743 promotes SC proliferation and the axon regeneration through miR-103-3p/BDNF after SNC.

scholarly journals The Amyloid Precursor-like Protein APL-1 Regulates Axon Regeneration

2018 ◽  
Author(s):  
Lewie Zeng ◽  
Rachid El Bejjani ◽  
Marc Hammarlund
Keyword(s):  
Motor Neurons ◽  
Neuronal Development ◽  
Axon Regeneration ◽  
Neuronal Response ◽  
Small Gtpase ◽  
C Elegans ◽  
Protein Levels ◽  
Mature Neurons ◽  
And Function

AbstractMembers of the Amyloid Precursor Protein (APP) family have important functions during neuronal development. However, their physiological functions in the mature nervous system are not fully understood. Here we use the C. elegans GABAergic motor neurons to study the post-developmental function of the APP-like protein APL-1 in vivo. We find that apl-1 has minimum roles in the maintenance of gross neuron morphology and function. However, we show that apl-1 is an inhibitor of axon regeneration, acting on mature neurons to limit regrowth in response to injury. The small GTPase Rab6/RAB-6.2 also inhibits regeneration, and does so in part by maintaining protein levels of APL-1. To inhibit regeneration, APL-1 functions via the E2 domain of its ectodomain; the cytoplasmic tail, transmembrane anchoring, and the E1 domain are not required for this function. Our data defines a novel role for APL-1 in modulating the neuronal response to injury.

scholarly journals Nogo-A expressed in Schwann cells impairs axonal regeneration after peripheral nerve injury

2002 ◽  
Vol 159 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Caroline Pot ◽  
Marjo Simonen ◽  
Oliver Weinmann ◽  
Lisa Schnell ◽  
Franziska Christ ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Axonal Regeneration ◽  
Neurite Growth ◽  
Sciatic Nerve Crush ◽  
Nerve Crush ◽  
Transgenic Expression ◽  
Growth Inhibitory ◽  
Brain And Spinal Cord

Înjured axons in mammalian peripheral nerves often regenerate successfully over long distances, in contrast to axons in the brain and spinal cord (CNS). Neurite growth-inhibitory proteins, including the recently cloned membrane protein Nogo-A, are enriched in the CNS, in particular in myelin. Nogo-A is not detectable in peripheral nerve myelin. Using regulated transgenic expression of Nogo-A in peripheral nerve Schwann cells, we show that axonal regeneration and functional recovery are impaired after a sciatic nerve crush. Nogo-A thus overrides the growth-permissive and -promoting effects of the lesioned peripheral nerve, demonstrating its in vivo potency as an inhibitor of axonal regeneration.

Polyethylene Glycol Rapidly Restores Axonal Integrity and Improves the Rate of Motor Behavior Recovery After Sciatic Nerve Crush Injury

2010 ◽  
Vol 104 (2) ◽  
pp. 695-703 ◽  
Author(s):  
Joshua M. Britt ◽  
Jacqueline R. Kane ◽  
Christopher S. Spaeth ◽  
Aleksej Zuzek ◽  
Garrett L. Robinson ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Motor Behavior ◽  
Clinical Problem ◽  
Sciatic Nerve Crush ◽  
Behavioral Recovery ◽  
Nerve Crush ◽  
Compound Action Potentials ◽  
Sciatic Functional Index

The inability to rapidly (within minutes to hours) improve behavioral function after severance of peripheral nervous system axons is an ongoing clinical problem. We have previously reported that polyethylene glycol (PEG) can rapidly restore axonal integrity (PEG-fusion) between proximal and distal segments of cut- and crush-severed rat axons in vitro and in vivo. We now report that PEG-fusion not only reestablishes the integrity of crush-severed rat sciatic axons as measured by the restored conduction of compound action potentials (CAPs) and the intraaxonal diffusion of fluorescent dye across the lesion site, but also produces more rapid recovery of appropriate hindlimb motor behaviors. Improvement in recovery occurred during the first few postoperative weeks for the foot fault (FF) asymmetry test and between week 2 and week 3 for the Sciatic Functional Index (SFI) based on analysis of footprints. That is, the FF test was the more sensitive indicator of early behavioral recovery, showing significant postoperative improvement of motor behavior in PEG-treated animals at 24–48 h. In contrast, the SFI more sensitively measured longer-term postoperative behavioral recovery and deficits at 4–8 wk, perhaps reflecting the development of fine (distal) motor control. These and other data show that PEG-fusion not only rapidly restores physiological and morphological axonal continuity, but also more quickly improves behavioral recovery.

Numerical patterns of axon regeneration that follow sciatic nerve crush in the neonatal rat

1987 ◽  
Vol 95 (2) ◽  
pp. 492-499 ◽  
Author(s):  
Chung-Bii Jenq ◽  
Lee Lan Jenq ◽  
Richard E. Coggeshall
Keyword(s):  
Sciatic Nerve ◽  
Axon Regeneration ◽  
Neonatal Rat ◽  
Sciatic Nerve Crush ◽  
Nerve Crush

scholarly journals Increased ER–mitochondria tethering promotes axon regeneration

2019 ◽  
Vol 116 (32) ◽  
pp. 16074-16079 ◽  
Author(s):  
Soyeon Lee ◽  
Wei Wang ◽  
Jinyeon Hwang ◽  
Uk Namgung ◽  
Kyung-Tai Min
Keyword(s):  
Axonal Regeneration ◽  
Therapeutic Strategy ◽  
Axon Regeneration ◽  
Lentiviral Vector ◽  
Sciatic Nerve Crush ◽  
Nerve Crush ◽  
Axon Injury ◽  
Physiological Importance ◽  
Atp Generation ◽  
Glucose Regulated Protein

Translocation of the endoplasmic reticulum (ER) and mitochondria to the site of axon injury has been shown to facilitate axonal regeneration; however, the existence and physiological importance of ER–mitochondria tethering in the injured axons are unknown. Here, we show that a protein linking ER to mitochondria, the glucose regulated protein 75 (Grp75), is locally translated at axon injury site following axotomy, and that overexpression of Grp75 in primary neurons increases ER–mitochondria tethering to promote regrowth of injured axons. We find that increased ER–mitochondria tethering elevates mitochondrial Ca2+ and enhances ATP generation, thereby promoting regrowth of injured axons. Furthermore, intrathecal delivery of lentiviral vector encoding Grp75 to an animal with sciatic nerve crush injury enhances axonal regeneration and functional recovery. Together, our findings suggest that increased ER–mitochondria tethering at axonal injury sites may provide a therapeutic strategy for axon regeneration.

scholarly journals Circ-Spidr enhances axon regeneration after peripheral nerve injury

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Susu Mao ◽  
Tao Huang ◽  
Yuanyuan Chen ◽  
Longxiang Shen ◽  
Shuoshuo Zhou ◽  
...  
Keyword(s):  
Nervous System ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Axon Regeneration ◽  
Neuronal Injury ◽  
Circular Rnas ◽  
Sciatic Nerve Crush ◽  
Drg Neurons ◽  
Nerve Crush

Abstract Accumulating evidence suggests that circular RNAs (circRNAs) are abundant and play critical roles in the nervous system. However, their functions in axon regeneration after neuronal injury are unclear. Due to its robust regeneration capacity, peripheral nervous system is ideal for seeking the regulatory circRNAs in axon regeneration. In the present work, we obtained an expression profile of circRNAs in dorsal root ganglions (DRGs) after rat sciatic nerve crush injury by RNA sequencing (RNA-Seq) and found the expression level of circ-Spidr was obviously increased using quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, circ-Spidr was proved to be a circular RNA enriched in the cytoplasm of DRG neurons. Through in vitro and in vivo experiments, we determined that down-regulation of circ-Spidr could suppress axon regeneration of DRG neurons after sciatic nerve injury partially through modulating PI3K-Akt signaling pathway. Together, our results reveal a crucial role for circRNAs in regulating axon regeneration after neuronal injury which may further serve as a potential therapeutic avenue for neuronal injury repair.

Sign in / Sign up

Export Citation Format

Share Document