Trehalose Augments Neuron Survival and Improves Recovery from Spinal Cord Injury via mTOR-Independent Activation of Autophagy
JournalOxidative Medicine and Cellular Longevity
MetadataShow full item record
AbstractSpinal cord injury (SCI) is a major cause of irreversible nerve injury and leads to serious tissue loss and neurological dysfunction. Thorough investigation of cellular mechanisms, such as autophagy, is crucial for developing novel and effective therapeutics. We administered trehalose, an mTOR-independent autophagy agonist, in SCI rats suffering from moderate compression injury to elucidate the relationship between autophagy and SCI and evaluate trehalose's therapeutic potential. 60 rats were divided into 4 groups and were treated with either control vehicle, trehalose, chloroquine, or trehalose + chloroquine 2 weeks prior to administration of moderate spinal cord crush injury. 20 additional sham rats were treated with control vehicle. H&E staining, Nissl staining, western blot, and immunofluorescence studies were conducted to examine nerve morphology and quantify autophagy and mitochondrial-dependent apoptosis at various time points after surgery. Functional recovery was assessed over a period of 4 weeks after surgery. Trehalose promotes autophagosome recruitment via an mTOR-independent pathway, enhances autophagy flux in neurons, inhibits apoptosis via the intrinsic mitochondria-dependent pathway, reduces lesion cavity expansion, decreases neuron loss, and ultimately improves functional recovery following SCI (all p < 0.05). Furthermore, these effects were diminished upon administration of chloroquine, an autophagy flux inhibitor, indicating that trehalose's beneficial effects were due largely to activation of autophagy. This study presents new evidence that autophagy plays a critical neuroprotective and neuroregenerative role in SCI, and that mTOR-independent activation of autophagy with trehalose leads to improved outcomes. Thus, trehalose has great translational potential as a novel therapeutic agent after SCI.
Rights/TermsCopyright © 2021 Kailiang Zhou et al.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16301
- Wnt-3a improves functional recovery through autophagy activation via inhibiting the mTOR signaling pathway after spinal cord injury.
- Authors: Gao K, Niu J, Dang X
- Issue date: 2020 Oct 15
- Insulin-like growth factor 1 promotes neurological functional recovery after spinal cord injury through inhibition of autophagy via the PI3K/Akt/mTOR signaling pathway.
- Authors: Zhang D, Yuan Y, Zhu J, Zhu D, Li C, Cui W, Wang L, Ma S, Duan S, Liu B
- Issue date: 2021 Nov
- TFE3, a potential therapeutic target for Spinal Cord Injury via augmenting autophagy flux and alleviating ER stress.
- Authors: Zhou K, Zheng Z, Li Y, Han W, Zhang J, Mao Y, Chen H, Zhang W, Liu M, Xie L, Zhang H, Xu H, Xiao J
- Issue date: 2020
- Metformin Improves Functional Recovery After Spinal Cord Injury via Autophagy Flux Stimulation.
- Authors: Zhang D, Xuan J, Zheng BB, Zhou YL, Lin Y, Wu YS, Zhou YF, Huang YX, Wang Q, Shen LY, Mao C, Wu Y, Wang XY, Tian NF, Xu HZ, Zhang XL
- Issue date: 2017 Jul
- Melatonin Enhances Autophagy and Reduces Apoptosis to Promote Locomotor Recovery in Spinal Cord Injury via the PI3K/AKT/mTOR Signaling Pathway.
- Authors: Li Y, Guo Y, Fan Y, Tian H, Li K, Mei X
- Issue date: 2019 Aug