Data for: Chronic stress hinders sensory axon regeneration via impairing mitochondrial cristae and OXPHOS
Data files
Jun 07, 2023 version files 57.74 MB
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glycolysis_gene_details_related_to_Fig_S4H.xlsm
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Pre-SCI_1w-vs-Pre-SCI_3w.all.annot.xls
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Pre-SCI_1w-vs-Pre-SCI_stress_1w.all.annot.xls
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Pre-SCI_3w-vs-Pre-SCI_stress_3w.all.annot.xls
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Pre-SCI_stress_1w-vs-Pre-SCI_stress_3w.all.annot.xls
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README.md
Abstract
Spinal cord injury (SCI) often leads to physical limitations, chronic pain, significant life changes, and social isolation, increasing the risk of chronic psychological stress such as anxiety and depression. Despite the recognition of the negative effects of chronic stress on SCI recovery, the mechanisms linking stress and regeneration are not fully understood. In this study, we examined the impact of chronic stress on primary sensory axon regeneration in a mouse model of preconditioning lesions. Our findings showed that chronic stress caused mitochondrial damage and energy crisis within primary sensory neurons, hindering the regrowth of their central axons. The stress hormone corticosterone was identified as a critical factor in this process, impacting satellite glial cells instead of neurons by suppressing Kir4.1 expression and leading to increased neuronal hyperactivity and elevated ROS levels. These high levels of ROS altered the shape of the mitochondrial cristae and disrupted ATP production, which is essential for powering axonal regeneration. Our results highlight the importance of addressing psychological stress in SCI patients to promote sensory-motor rehabilitation.
Methods
To investigate how psychological stress influences axon regeneration, we employed a combination of the preconditioning spinal cord injury model and the unpredictable chronic mild stress model. Our experimental design comprised two mouse models: Pre-SCI and Pre-SCI+stress.
In these models, we conducted transcriptomic analyses on the lumbar 4-6 ganglions (L4-L6) dorsal root ganglia (DRGs) at two distinct post-injury time points, specifically 1-week post-injury (1 wpi) and 3 weeks post-injury (3 wpi), utilizing RNA-sequencing.
For the Pre-SCI_1w and Pre-SCI+stress_1w groups, DRGs were collected immediately after spinal cord injury, which occurred one week after peripheral nerve lesions. The only distinction between these two groups was the additional 1-week stress exposure given to the Pre-SCI+stress_1w group.Similarly, for the Pre-SCI_3w and Pre-SCI+stress_3w groups, DRGs were collected two weeks post-spinal cord injury, which equates to three weeks after peripheral nerve lesions. The Pre-SCI+stress_3w group, however, also underwent a 3-week stress exposure.