PGC-1α in the hippocampus mediates depressive-like and stress-coping behaviours and regulates excitatory synapses in the dentate gyrus in mice
Copyright © 2024 Elsevier Ltd. All rights reserved..
Decreased hippocampal synaptic plasticity is an important pathological change in stress-related mood disorders, including major depressive disorder. However, the underlying mechanism is unclear. PGC-1α, a transcriptional coactivator, is a key factor in synaptic plasticity. We investigated the relationships between changes in hippocampal PGC-1α expression and depressive-like and stress-coping behaviours, and whether they are related to hippocampal synapses. Adeno-associated virus was used to alter hippocampal PGC-1α expression in male C57BL/6 mice. The sucrose preference test and forced swimming test were used to assess their depressive-like and stress-coping behaviours, respectively. Immunohistochemistry and stereology were used to calculate the total number of excitatory synapses in each hippocampal subregion (the cornu ammonis (CA) 1, CA3, and dentate gyrus). Immunofluorescence was used to visualize the changes in dendritic structure. Western blotting was used to detect the expression of hippocampal PGC-1α and mitochondrial-associated proteins, such as UCP2, NRF1 and mtTFAs. Our results showed that mice with downregulated PGC-1α expression in the hippocampus exhibited depressive-like and passive stress-coping behaviours, while mice with upregulated PGC-1α in the hippocampus exhibited increased stress-coping behaviours. Moreover, the downregulation of hippocampal PGC-1α expression resulted in a decrease in the number of excitatory synapses in the DG and in the protein expression of UCP2 in the hippocampus. Alternatively, upregulation of hippocampal PGC-1α yielded the opposite results. This suggests that hippocampal PGC-1α is involved in regulating depressive-like and stress-coping behaviours and modulating the number of excitatory synapses in the DG. This provides new insight for the development of antidepressants.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:250 |
|---|---|
| Enthalten in: |
Neuropharmacology - 250(2024) vom: 01. Apr., Seite 109908 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Deng, Yuhui [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Depression |
|---|
| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 11.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.neuropharm.2024.109908 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369825608 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369825608 | ||
| 003 | DE-627 | ||
| 005 | 20240411232456.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240317s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.neuropharm.2024.109908 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1372.xml |
| 035 | |a (DE-627)NLM369825608 | ||
| 035 | |a (NLM)38492883 | ||
| 035 | |a (PII)S0028-3908(24)00077-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Deng, Yuhui |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a PGC-1α in the hippocampus mediates depressive-like and stress-coping behaviours and regulates excitatory synapses in the dentate gyrus in mice |
| 264 | 1 | |c 2024 | |
| 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 08.04.2024 | ||
| 500 | |a Date Revised 11.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Decreased hippocampal synaptic plasticity is an important pathological change in stress-related mood disorders, including major depressive disorder. However, the underlying mechanism is unclear. PGC-1α, a transcriptional coactivator, is a key factor in synaptic plasticity. We investigated the relationships between changes in hippocampal PGC-1α expression and depressive-like and stress-coping behaviours, and whether they are related to hippocampal synapses. Adeno-associated virus was used to alter hippocampal PGC-1α expression in male C57BL/6 mice. The sucrose preference test and forced swimming test were used to assess their depressive-like and stress-coping behaviours, respectively. Immunohistochemistry and stereology were used to calculate the total number of excitatory synapses in each hippocampal subregion (the cornu ammonis (CA) 1, CA3, and dentate gyrus). Immunofluorescence was used to visualize the changes in dendritic structure. Western blotting was used to detect the expression of hippocampal PGC-1α and mitochondrial-associated proteins, such as UCP2, NRF1 and mtTFAs. Our results showed that mice with downregulated PGC-1α expression in the hippocampus exhibited depressive-like and passive stress-coping behaviours, while mice with upregulated PGC-1α in the hippocampus exhibited increased stress-coping behaviours. Moreover, the downregulation of hippocampal PGC-1α expression resulted in a decrease in the number of excitatory synapses in the DG and in the protein expression of UCP2 in the hippocampus. Alternatively, upregulation of hippocampal PGC-1α yielded the opposite results. This suggests that hippocampal PGC-1α is involved in regulating depressive-like and stress-coping behaviours and modulating the number of excitatory synapses in the DG. This provides new insight for the development of antidepressants | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Depression | |
| 650 | 4 | |a Hippocampus | |
| 650 | 4 | |a PGC-1α | |
| 650 | 4 | |a Stereology | |
| 650 | 4 | |a Synapse | |
| 650 | 7 | |a Ppargc1a protein, mouse |2 NLM | |
| 700 | 1 | |a Liang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yuhan |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Peilin |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Yijing |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Yanmin |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Yong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neuropharmacology |d 1970 |g 250(2024) vom: 01. Apr., Seite 109908 |w (DE-627)NLM000008486 |x 1873-7064 |7 nnns |
| 773 | 1 | 8 | |g volume:250 |g year:2024 |g day:01 |g month:04 |g pages:109908 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.neuropharm.2024.109908 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 250 |j 2024 |b 01 |c 04 |h 109908 | ||