A New Perspective on Ameliorating Depression-Like Behaviors : Suppressing Neuroinflammation by Upregulating PGC-1α
Inflammation plays an important role in depression pathology, making it a promising target for ameliorating depression-like behaviors. The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a transcriptional coactivator being able to constrain inflammatory events through NF-κB signaling. However, the role of PGC-1α in depression is not yet clear. This study was designed to investigate the role of PGC-1α in depression and explore the underlying mechanisms. Mice modeled with chronic unpredictable mild stimulation (CUMS) were explored for the relationship between depression-like behaviors and PGC-1α. Baicalin was used to evaluate the effect regulating PGC-1α. Furthermore, the anti-neuroinflammatory effect of baicalin was investigated both in BV2-SH-SY5Y co-culture system and in mice by LPS challenge. The role of PGC-1α in neuroinflammation was explored in cell co-culture systems under gene silencing conditions targeting NF-κB signaling. We found that the expression of PGC-1α was inhibited in the hippocampus of mice exposed to CUMS or LPS, while baicalin could increase the expression of PGC-1α and alleviate the depression-like behaviors. Furthermore, baicalin attenuated neuroinflammation in the hippocampus of mice and BV2-SH-SY5Y co-culture system by LPS challenge via regulating NF-κB signaling; however, knockdown of the PGC-1α could reverse the effect of baicalin on neuroinflammation and NF-κB signaling. Our results revealed a vital role for PGC-1α in attenuating neuroinflammation in depression, indicating that PGC-1α might be a therapeutic target for depression.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
|---|---|
| Enthalten in: |
Neurotoxicity research - 39(2021), 3 vom: 06. Juni, Seite 872-885 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Fu, Xinxin [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 29.11.2021 Date Revised 21.10.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s12640-020-00292-z |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM315955384 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM315955384 | ||
| 003 | DE-627 | ||
| 005 | 20231225160032.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s12640-020-00292-z |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1053.xml |
| 035 | |a (DE-627)NLM315955384 | ||
| 035 | |a (NLM)33025359 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Fu, Xinxin |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A New Perspective on Ameliorating Depression-Like Behaviors |b Suppressing Neuroinflammation by Upregulating PGC-1α |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 29.11.2021 | ||
| 500 | |a Date Revised 21.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Inflammation plays an important role in depression pathology, making it a promising target for ameliorating depression-like behaviors. The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a transcriptional coactivator being able to constrain inflammatory events through NF-κB signaling. However, the role of PGC-1α in depression is not yet clear. This study was designed to investigate the role of PGC-1α in depression and explore the underlying mechanisms. Mice modeled with chronic unpredictable mild stimulation (CUMS) were explored for the relationship between depression-like behaviors and PGC-1α. Baicalin was used to evaluate the effect regulating PGC-1α. Furthermore, the anti-neuroinflammatory effect of baicalin was investigated both in BV2-SH-SY5Y co-culture system and in mice by LPS challenge. The role of PGC-1α in neuroinflammation was explored in cell co-culture systems under gene silencing conditions targeting NF-κB signaling. We found that the expression of PGC-1α was inhibited in the hippocampus of mice exposed to CUMS or LPS, while baicalin could increase the expression of PGC-1α and alleviate the depression-like behaviors. Furthermore, baicalin attenuated neuroinflammation in the hippocampus of mice and BV2-SH-SY5Y co-culture system by LPS challenge via regulating NF-κB signaling; however, knockdown of the PGC-1α could reverse the effect of baicalin on neuroinflammation and NF-κB signaling. Our results revealed a vital role for PGC-1α in attenuating neuroinflammation in depression, indicating that PGC-1α might be a therapeutic target for depression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Baicalin | |
| 650 | 4 | |a Depression | |
| 650 | 4 | |a Neuroinflammation | |
| 650 | 4 | |a PGC-1α/NF-κB pathway | |
| 650 | 7 | |a Anti-Inflammatory Agents, Non-Steroidal |2 NLM | |
| 650 | 7 | |a Flavonoids |2 NLM | |
| 650 | 7 | |a Inflammation Mediators |2 NLM | |
| 650 | 7 | |a Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha |2 NLM | |
| 650 | 7 | |a Ppargc1a protein, mouse |2 NLM | |
| 650 | 7 | |a baicalin |2 NLM | |
| 650 | 7 | |a 347Q89U4M5 |2 NLM | |
| 700 | 1 | |a Jiao, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jiayu |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Xueyang |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Shiping |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Zhanqiang |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neurotoxicity research |d 1999 |g 39(2021), 3 vom: 06. Juni, Seite 872-885 |w (DE-627)NLM124802664 |x 1476-3524 |7 nnns |
| 773 | 1 | 8 | |g volume:39 |g year:2021 |g number:3 |g day:06 |g month:06 |g pages:872-885 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s12640-020-00292-z |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 39 |j 2021 |e 3 |b 06 |c 06 |h 872-885 | ||