Investigation of Injury- and Paracrine-Induced Sensory Neuron Senescence in a Chronic Pain Model
Abstract/Contents
- Abstract
- Chronic pain is a significant public health issue and largely affects older members of the population. As people age, senescent cells, which do not divide but resist apoptosis, accumulate in response to stressors, and the senescence-associated secretory phenotype (SASP) may be a contributing and compounding factor to chronic pain. Preliminary data from the Tawfik Lab suggest that sensory neurons, whose cell bodies reside in the dorsal root ganglia (DRG), undergo cellular senescence following peripheral injury. However, it is unknown whether injury directly induces senescence and, further, whether injured senescent cells induce senescence in uninjured, neighboring cells via paracrine senescence. The objectives of this thesis were to (1) investigate cellular senescence of injured and uninjured neurons in the DRG at two chronic timepoints following spared nerve injury (SNI) and (2) investigate whether paracrine senescence occurs after SNI and is potentially exacerbated in aged DRG. RNAscope and immunohistochemistry methods were used to detect senescent cells in the DRG following SNI, and quantitative analysis was performed using ImageJ. A novel method was developed and used to categorize uninjured senescent neurons as paracrine induced based on their proximity to injured IL6+ senescent neurons. At 3 weeks post-SNI, more senescent neurons were observed in the young compared to aged DRG. By 7 weeks post-SNI, the percent of senescent neurons had declined and no difference was observed between young and aged DRG. Also at this timepoint, the ratio of uninjured to injured senescent neurons increased in young and aged DRG, and a slight increase in paracrine-induced senescent neurons was observed in aged tissue. Interestingly, however, paracrine-induced senescent neurons only comprised a minority of uninjured senescent cells. These findings suggest that senescence may be induced in uninjured neurons through processes other than IL6-induced paracrine senescence that have yet to be explored in the DRG.
Description
| Type of resource | text |
|---|---|
| Date modified | December 5, 2022 |
| Publication date | May 5, 2022; May 2022 |
Creators/Contributors
| Author | Jordan, Claire |
|---|---|
| Thesis advisor | Tawfik, Vivianne |
| Thesis advisor | Chen, Xiaoke |
| Thesis advisor | Skotheim, Jan |
| Degree granting institution | Stanford University, Department of Biology |
Subjects
| Subject | Biology |
|---|---|
| Subject | Aging |
| Subject | Senescence |
| Subject | Spared nerve injury |
| Subject | Paracrine senescence |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
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- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 4.0 International license (CC BY-NC).
Preferred citation
- Preferred citation
- Jordan, C. and Tawfik, V. (2022). Investigation of Injury- and Paracrine-Induced Sensory Neuron Senescence in a Chronic Pain Model. Stanford Digital Repository. Available at https://purl.stanford.edu/gq584rb1244
Collection
Undergraduate Theses, Department of Biology, 2021-2022
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- cejordan@stanford.edu
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