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Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) via regulating the synaptic plasticity in hippocampus.
Wei, Qian-Qian; Yin, Yong-Yu; Qiao, Yong-Xing; Ni, Han; Han, Shuo-Yu; Yao, Yishan; Li, Yun-Feng; Zhang, Li-Ming; Li, Junxu.
Afiliación
  • Wei QQ; Department of Basic Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, China; Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China.
  • Yin YY; Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China.
  • Qiao YX; Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China; Hebei University of Science and Technology, Shijiazhuang, China.
  • Ni H; Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China; Hebei University of Science and Technology, Shijiazhuang, China.
  • Han SY; The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Yao Y; Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China.
  • Li YF; Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China; Beijing Institute of Basic Medical Sciences, Beijing, China.
  • Zhang LM; Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China. Electronic address: zhanglm0308@163.com.
  • Li J; Department of Basic Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, China. Electronic address: junxuli@gmail.com.
Eur J Pharmacol ; 969: 176394, 2024 Apr 15.
Article en En | MEDLINE | ID: mdl-38331342
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ansiolíticos / Imidazoles Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ansiolíticos / Imidazoles Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos