Dataset Information

Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3-mediated anti-oxidative stress and mitophagy.

ABSTRACT:

Introduction

Spinal cord injury (SCI) is a central nervous system injury that is primarily traumatic and manifests as motor, sensory, and autonomic dysfunction below the level of damage. Our previous studies confirmed the ability of zinc to protect mitochondria, protect neurons and promote spinal cord recovery. However, the role of zinc in Parthanatos is unknown.

Aim

We investigated the effects of zinc in Parthanatos from oxidative stress and mitophagy. We elucidated the role of SIRT3 in providing new ideas for treating spinal cord injury.

The results

Zinc protected SCI mice by regulating Parthanatos. On the one hand, zinc eliminated ROS directly through SIRT3 deacetylation targeting SOD2 to alleviate Parthanatos. On the other hand, zinc eliminated ROS indirectly through SIRT3-mediated promotion of mitophagy to alleviate Parthanatos.

Conclusion

Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3-mediated anti-oxidative stress and mitophagy.

SUBMITTER: Jiang D

PROVIDER: S-EPMC10493669 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3-mediated anti-oxidative stress and mitophagy.

Jiang Dingyuan D Yang Xu X Ge Minghao M Hu Hengshuo H Xu Chang C Wen Shan S Deng Hao H Mei Xifan X

CNS neuroscience & therapeutics 20230417 10

<h4>Introduction</h4>Spinal cord injury (SCI) is a central nervous system injury that is primarily traumatic and manifests as motor, sensory, and autonomic dysfunction below the level of damage. Our previous studies confirmed the ability of zinc to protect mitochondria, protect neurons and promote spinal cord recovery. However, the role of zinc in Parthanatos is unknown.<h4>Aim</h4>We investigated the effects of zinc in Parthanatos from oxidative stress and mitophagy. We elucidated the role of S ...[more]

PMID: 37063066

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Project description:Functional recovery after spinal cord injury (SCI) often proves difficult as physical and mental barriers bar survivors from enacting their designated rehabilitation programs. We recently demonstrated that adult mice administered gabapentinoids, clinically approved drugs prescribed to mitigate chronic neuropathic pain, recovered upper extremity function following cervical SCI. Given that rehabilitative training enhances neuronal plasticity and promotes motor recovery, we hypothesized that the combination of an aerobic-based rehabilitation regimen like treadmill training with gabapentin (GBP) administration will maximize recovery in SCI mice by strengthening synaptic connections along the sensorimotor axis. Whereas mice administered GBP recovered forelimb functions over the course of weeks and months following SCI, no additive forelimb recovery as the result of voluntary treadmill training was noted in these mice. To our surprise, we also failed to find an additive effect in mice administered vehicle. As motivation is crucial in rehabilitation interventions, we scored active engagement toward the rehabilitation protocol and found that mice administered GBP were consistently participating in the rehabilitation program. In contrast, mice administered vehicle exhibited a steep decline in participation, especially at chronic time points. Whereas neuroinflammatory gene expression profiles were comparable between experimental conditions, we discovered that mice administered GBP had increased hippocampal neurogenesis and exhibited less anxiety-like behavior after SCI. We also found that an external, social motivator effectively rescues participation in mice administered vehicle and promotes forelimb recovery after chronic SCI. Thus, not only does a clinically relevant treatment strategy preclude the deterioration of mental health after chronic SCI, but group intervention strategies may prove to be physically and emotionally beneficial for SCI individuals.

Dataset Information

Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3-mediated anti-oxidative stress and mitophagy.

Introduction

Aim

The results

Conclusion

Publications

Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3-mediated anti-oxidative stress and mitophagy.

Similar Datasets

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