Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) via regulating the synaptic plasticity in hippocampus
Copyright © 2024. Published by Elsevier B.V..
TSPO, translocator protein (18 kDa) ligands have demonstrated consistent antidepression and anxiolytic effects in several preclinical studies. This study aimed to examine whether YL-IPA08[N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-ichlorophenyl) -7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, could alleviate anxiety-related behaviors induced by electric shock (ES) and investigate its underlying mechanism. As expected, we showed that chronic treatment with YL-IPA08 significantly reversed anxiety-related behaviors induced by electrical stimulation (0.5 mA, 12 times, duration 1s, interval 10s) exposure. Using the analysis of RNA-sequencing (RNA-seq) technology, it was found that the differential genes associated with the anxiolytic effect of YL-IPA08 were mainly related to synaptic plasticity. Furthermore, YL-IPA08 restored the decreased levels of brain-derived neurotrophic factor (BDNF), synapse-related protein (e.g. synapsin-1 and post-synaptic density95, PSD95), and the number of doublecortin (DCX) + neurons in the hippocampus of post-ES mice. In addition, YL-IPA08 also enhanced the dendritic complexity and dendritic spine density of hippocampal dentate gyrus (DG) granule neurons. Meanwhile, the induction of long-term potentiation (LTP) was significantly enhanced by YL-IPA08. In summary, the findings from the current study showed that YL-IPA08 exerted a clear anxiolytic effect, which might be partially mediated by promoting hippocampal neuroplasticity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:969 |
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| Enthalten in: |
European journal of pharmacology - 969(2024) vom: 15. März, Seite 176394 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wei, Qian-Qian [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejphar.2024.176394 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Wei, Qian-Qian |e verfasserin |4 aut | |
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| 520 | |a TSPO, translocator protein (18 kDa) ligands have demonstrated consistent antidepression and anxiolytic effects in several preclinical studies. This study aimed to examine whether YL-IPA08[N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-ichlorophenyl) -7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, could alleviate anxiety-related behaviors induced by electric shock (ES) and investigate its underlying mechanism. As expected, we showed that chronic treatment with YL-IPA08 significantly reversed anxiety-related behaviors induced by electrical stimulation (0.5 mA, 12 times, duration 1s, interval 10s) exposure. Using the analysis of RNA-sequencing (RNA-seq) technology, it was found that the differential genes associated with the anxiolytic effect of YL-IPA08 were mainly related to synaptic plasticity. Furthermore, YL-IPA08 restored the decreased levels of brain-derived neurotrophic factor (BDNF), synapse-related protein (e.g. synapsin-1 and post-synaptic density95, PSD95), and the number of doublecortin (DCX) + neurons in the hippocampus of post-ES mice. In addition, YL-IPA08 also enhanced the dendritic complexity and dendritic spine density of hippocampal dentate gyrus (DG) granule neurons. Meanwhile, the induction of long-term potentiation (LTP) was significantly enhanced by YL-IPA08. In summary, the findings from the current study showed that YL-IPA08 exerted a clear anxiolytic effect, which might be partially mediated by promoting hippocampal neuroplasticity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anxiety | |
| 650 | 4 | |a Hippocampus | |
| 650 | 4 | |a Synaptic plasticity | |
| 650 | 4 | |a TSPO | |
| 650 | 7 | |a Anti-Anxiety Agents |2 NLM | |
| 650 | 7 | |a N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-chlorophenyl)-7-methylimidazo(1,2-a)pyridine-3-acetamide |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 650 | 7 | |a Imidazoles |2 NLM | |
| 700 | 1 | |a Yin, Yong-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Qiao, Yong-Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Han |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Shuo-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Yishan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yun-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Li-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Junxu |e verfasserin |4 aut | |
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