Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury
Abstract Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD). Augmented fear is a defining characteristic of PTSD, and the amygdala is considered the main brain region to process fear. The mechanism by which the amygdala is involved in fear conditioning after TBI i...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-03-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202104112 |
| _version_ | 1818909745575100416 |
|---|---|
| author | Yingwu Shi Xun Wu Jinpeng Zhou Wenxing Cui Jin Wang Qing Hu Shenghao Zhang Liying Han Meixuan Zhou Jianing Luo Qiang Wang Haixiao Liu Dayun Feng Shunnan Ge Yan Qu |
| author_facet | Yingwu Shi Xun Wu Jinpeng Zhou Wenxing Cui Jin Wang Qing Hu Shenghao Zhang Liying Han Meixuan Zhou Jianing Luo Qiang Wang Haixiao Liu Dayun Feng Shunnan Ge Yan Qu |
| author_sort | Yingwu Shi |
| collection | DOAJ |
| description | Abstract Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD). Augmented fear is a defining characteristic of PTSD, and the amygdala is considered the main brain region to process fear. The mechanism by which the amygdala is involved in fear conditioning after TBI is still unclear. Using single‐nucleus RNA sequencing (snRNA‐seq), transcriptional changes in cells in the amygdala after TBI are investigated. In total, 72 328 nuclei are obtained from the sham and TBI groups. 7 cell types, and analysis of differentially expressed genes (DEGs) reveals widespread transcriptional changes in each cell type after TBI are identified. In in vivo experiments, it is demonstrated that Decorin (Dcn) expression in the excitatory neurons of the amygdala significantly increased after TBI, and Dcn knockout in the amygdala mitigates TBI‐associated fear conditioning. Of note, this effect is caused by a Dcn‐mediated decrease in the expression of perineuronal nets (PNNs), which affect the glutamate‐γ‐aminobutyric acid balance in the amygdala. Finally, the results suggest that Dcn functions by interacting with collagen VI α3 (Col6a3). Consequently, the findings reveal transcriptional changes in different cell types of the amygdala after TBI and provide direct evidence that Dcn relieves fear conditioning by regulating PNNs. |
| first_indexed | 2024-12-19T22:31:48Z |
| format | Article |
| id | doaj.art-327127728b9144b3b59c0383c00faa21 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-19T22:31:48Z |
| publishDate | 2022-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-327127728b9144b3b59c0383c00faa212022-12-21T20:03:19ZengWileyAdvanced Science2198-38442022-03-0197n/an/a10.1002/advs.202104112Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain InjuryYingwu Shi0Xun Wu1Jinpeng Zhou2Wenxing Cui3Jin Wang4Qing Hu5Shenghao Zhang6Liying Han7Meixuan Zhou8Jianing Luo9Qiang Wang10Haixiao Liu11Dayun Feng12Shunnan Ge13Yan Qu14Department of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaSchool of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200240 ChinaDepartment of Neurosurgery West Theater General Hospital Chengdu Sichuan 610083 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaDepartment of Neurosurgery Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 ChinaAbstract Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD). Augmented fear is a defining characteristic of PTSD, and the amygdala is considered the main brain region to process fear. The mechanism by which the amygdala is involved in fear conditioning after TBI is still unclear. Using single‐nucleus RNA sequencing (snRNA‐seq), transcriptional changes in cells in the amygdala after TBI are investigated. In total, 72 328 nuclei are obtained from the sham and TBI groups. 7 cell types, and analysis of differentially expressed genes (DEGs) reveals widespread transcriptional changes in each cell type after TBI are identified. In in vivo experiments, it is demonstrated that Decorin (Dcn) expression in the excitatory neurons of the amygdala significantly increased after TBI, and Dcn knockout in the amygdala mitigates TBI‐associated fear conditioning. Of note, this effect is caused by a Dcn‐mediated decrease in the expression of perineuronal nets (PNNs), which affect the glutamate‐γ‐aminobutyric acid balance in the amygdala. Finally, the results suggest that Dcn functions by interacting with collagen VI α3 (Col6a3). Consequently, the findings reveal transcriptional changes in different cell types of the amygdala after TBI and provide direct evidence that Dcn relieves fear conditioning by regulating PNNs.https://doi.org/10.1002/advs.202104112amygdaladecorinfear conditioningperineuronal netstraumatic brain injury |
| spellingShingle | Yingwu Shi Xun Wu Jinpeng Zhou Wenxing Cui Jin Wang Qing Hu Shenghao Zhang Liying Han Meixuan Zhou Jianing Luo Qiang Wang Haixiao Liu Dayun Feng Shunnan Ge Yan Qu Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury Advanced Science amygdala decorin fear conditioning perineuronal nets traumatic brain injury |
| title | Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury |
| title_full | Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury |
| title_fullStr | Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury |
| title_full_unstemmed | Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury |
| title_short | Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury |
| title_sort | single nucleus rna sequencing reveals that decorin expression in the amygdala regulates perineuronal nets expression and fear conditioning response after traumatic brain injury |
| topic | amygdala decorin fear conditioning perineuronal nets traumatic brain injury |
| url | https://doi.org/10.1002/advs.202104112 |
| work_keys_str_mv | AT yingwushi singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT xunwu singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT jinpengzhou singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT wenxingcui singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT jinwang singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT qinghu singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT shenghaozhang singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT liyinghan singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT meixuanzhou singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT jianingluo singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT qiangwang singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT haixiaoliu singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT dayunfeng singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT shunnange singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury AT yanqu singlenucleusrnasequencingrevealsthatdecorinexpressionintheamygdalaregulatesperineuronalnetsexpressionandfearconditioningresponseaftertraumaticbraininjury |