Nicorandil Ameliorates Depression‐Like Behaviors After Traumatic Brain Injury by Suppressing Ferroptosis Through the SLC7A11/GPX4 Axis in the Hippocampus
ABSTRACT Introduction Depression is a prevalent and significant psychological consequence of traumatic brain injury (TBI). Ferroptosis, an iron‐dependent form of regulated cell death, exacerbates the neurological damage associated with TBI. This study investigates whether nicorandil, a potassium cha...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Brain and Behavior |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/brb3.70199 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832582642797641728 |
|---|---|
| author | Yao‐Ran Tu Ming Tan Yao Li De‐Quan Hong Fan Niu |
| author_facet | Yao‐Ran Tu Ming Tan Yao Li De‐Quan Hong Fan Niu |
| author_sort | Yao‐Ran Tu |
| collection | DOAJ |
| description | ABSTRACT Introduction Depression is a prevalent and significant psychological consequence of traumatic brain injury (TBI). Ferroptosis, an iron‐dependent form of regulated cell death, exacerbates the neurological damage associated with TBI. This study investigates whether nicorandil, a potassium channel opener with nitrate‐like properties known for its antioxidative and neuroprotective effects, can mitigate depression‐like behaviors following TBI by modulating ferroptosis. Methods A controlled cortical impact (CCI) device was used to establish the TBI model. Depression‐like behaviors in rats were assessed using the sucrose preference test (SPT), the tail suspension test (TST), and the forced swimming test (FST). The antioxidant system, lipid peroxidation, and ferroptosis levels were evaluated. The SLC7A11/GPX4 axis was analyzed using quantitative real‐time PCR (qRT‐PCR) and Western blot analysis. Results Nicorandil administration significantly ameliorated depression‐like behaviors in rats with TBI. Nicorandil administration also effectively restored the antioxidant system, substantially reduced lipid peroxidation, and attenuated ferroptosis in the hippocampus of rats with TBI. Mechanistically, nicorandil administration promoted the SLC7A11/GPX4 axis in the hippocampus of rats with TBI. Crucially, knockdown of hippocampal SLC7A11 abrogated the protective effects of nicorandil on depression‐like behaviors, lipid peroxidation, and ferroptosis in the hippocampus of rats with TBI. Conclusion These findings indicate that nicorandil ameliorates depression‐like behaviors following TBI by inhibiting hippocampal ferroptosis through the activation of the SLC7A11/GPX4 axis. |
| format | Article |
| id | doaj-art-64441ded7ea141a5952e510a9bb619cf |
| institution | Kabale University |
| issn | 2162-3279 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj-art-64441ded7ea141a5952e510a9bb619cf2025-01-29T13:36:39ZengWileyBrain and Behavior2162-32792025-01-01151n/an/a10.1002/brb3.70199Nicorandil Ameliorates Depression‐Like Behaviors After Traumatic Brain Injury by Suppressing Ferroptosis Through the SLC7A11/GPX4 Axis in the HippocampusYao‐Ran Tu0Ming Tan1Yao Li2De‐Quan Hong3Fan Niu4Department of Emergency and Trauma Center Nanchang First Hospital Nanchang Jiangxi ChinaDepartment of Emergency and Trauma Center Nanchang First Hospital Nanchang Jiangxi ChinaDepartment of Emergency and Trauma Center Nanchang First Hospital Nanchang Jiangxi ChinaDepartment of Emergency and Trauma Center Nanchang First Hospital Nanchang Jiangxi ChinaDepartment of Emergency and Trauma Center Nanchang First Hospital Nanchang Jiangxi ChinaABSTRACT Introduction Depression is a prevalent and significant psychological consequence of traumatic brain injury (TBI). Ferroptosis, an iron‐dependent form of regulated cell death, exacerbates the neurological damage associated with TBI. This study investigates whether nicorandil, a potassium channel opener with nitrate‐like properties known for its antioxidative and neuroprotective effects, can mitigate depression‐like behaviors following TBI by modulating ferroptosis. Methods A controlled cortical impact (CCI) device was used to establish the TBI model. Depression‐like behaviors in rats were assessed using the sucrose preference test (SPT), the tail suspension test (TST), and the forced swimming test (FST). The antioxidant system, lipid peroxidation, and ferroptosis levels were evaluated. The SLC7A11/GPX4 axis was analyzed using quantitative real‐time PCR (qRT‐PCR) and Western blot analysis. Results Nicorandil administration significantly ameliorated depression‐like behaviors in rats with TBI. Nicorandil administration also effectively restored the antioxidant system, substantially reduced lipid peroxidation, and attenuated ferroptosis in the hippocampus of rats with TBI. Mechanistically, nicorandil administration promoted the SLC7A11/GPX4 axis in the hippocampus of rats with TBI. Crucially, knockdown of hippocampal SLC7A11 abrogated the protective effects of nicorandil on depression‐like behaviors, lipid peroxidation, and ferroptosis in the hippocampus of rats with TBI. Conclusion These findings indicate that nicorandil ameliorates depression‐like behaviors following TBI by inhibiting hippocampal ferroptosis through the activation of the SLC7A11/GPX4 axis.https://doi.org/10.1002/brb3.70199depressionferroptosisnicorandilthe SLC7A11/GPX4 axistraumatic brain injury |
| spellingShingle | Yao‐Ran Tu Ming Tan Yao Li De‐Quan Hong Fan Niu Nicorandil Ameliorates Depression‐Like Behaviors After Traumatic Brain Injury by Suppressing Ferroptosis Through the SLC7A11/GPX4 Axis in the Hippocampus Brain and Behavior depression ferroptosis nicorandil the SLC7A11/GPX4 axis traumatic brain injury |
| title | Nicorandil Ameliorates Depression‐Like Behaviors After Traumatic Brain Injury by Suppressing Ferroptosis Through the SLC7A11/GPX4 Axis in the Hippocampus |
| title_full | Nicorandil Ameliorates Depression‐Like Behaviors After Traumatic Brain Injury by Suppressing Ferroptosis Through the SLC7A11/GPX4 Axis in the Hippocampus |
| title_fullStr | Nicorandil Ameliorates Depression‐Like Behaviors After Traumatic Brain Injury by Suppressing Ferroptosis Through the SLC7A11/GPX4 Axis in the Hippocampus |
| title_full_unstemmed | Nicorandil Ameliorates Depression‐Like Behaviors After Traumatic Brain Injury by Suppressing Ferroptosis Through the SLC7A11/GPX4 Axis in the Hippocampus |
| title_short | Nicorandil Ameliorates Depression‐Like Behaviors After Traumatic Brain Injury by Suppressing Ferroptosis Through the SLC7A11/GPX4 Axis in the Hippocampus |
| title_sort | nicorandil ameliorates depression like behaviors after traumatic brain injury by suppressing ferroptosis through the slc7a11 gpx4 axis in the hippocampus |
| topic | depression ferroptosis nicorandil the SLC7A11/GPX4 axis traumatic brain injury |
| url | https://doi.org/10.1002/brb3.70199 |
| work_keys_str_mv | AT yaorantu nicorandilamelioratesdepressionlikebehaviorsaftertraumaticbraininjurybysuppressingferroptosisthroughtheslc7a11gpx4axisinthehippocampus AT mingtan nicorandilamelioratesdepressionlikebehaviorsaftertraumaticbraininjurybysuppressingferroptosisthroughtheslc7a11gpx4axisinthehippocampus AT yaoli nicorandilamelioratesdepressionlikebehaviorsaftertraumaticbraininjurybysuppressingferroptosisthroughtheslc7a11gpx4axisinthehippocampus AT dequanhong nicorandilamelioratesdepressionlikebehaviorsaftertraumaticbraininjurybysuppressingferroptosisthroughtheslc7a11gpx4axisinthehippocampus AT fanniu nicorandilamelioratesdepressionlikebehaviorsaftertraumaticbraininjurybysuppressingferroptosisthroughtheslc7a11gpx4axisinthehippocampus |