AI Article Synopsis
- - The study investigates the antidepressant-like effects of YL-IPA08, a new ligand that targets the translocator protein (TSPO), using a rat model of chronic unpredictable stress (CUS) to simulate depression.
- - Results showed that YL-IPA08 improved locomotor activity, increased sucrose preference, and shortened time to eat in stressed rats, indicating reduced depressive-like behaviors.
- - Additionally, YL-IPA08 elevated levels of progesterone and allopregnanolone in key brain areas, reversed damage to neuronal structures, and corrected hormone regulation issues, suggesting its potential effectiveness in treating depression through multiple cellular mechanisms.
Article Abstract
The present study aimed to examine the molecular and cellular mechanisms underlying the antidepressant-like effect of YL-IPA08, a novel TSPO ligand designed and synthesized at our institute. We firstly used the chronic unpredictable stress (CUS) procedure of rats, a well validated stress-related animal model of depression, to further determine the antidepressant-like of YL-IPA08. And we found that YL-IPA08 caused significant suppression of inhibiting of locomotor activity, reducing the sucrose preference and increasing the latency to eat induced by CUS. In addition, YL-IPA08 treatment increased the levels of progesterone and allopregnanolone in the hippocampus and prefrontal cortex of post- CUS rats. Furthermore, long-term YL-IPA08 administration reversed dendritic shrinkage, down-regulation of neurotrophic signaling pathway within the hippocampus, as well as HPA dysfunctions simultaneously observed in the CUS rats. Collectively, the evidence presented above supports the notion that binding to TSPO and the subsequent synthesis of neurosteroid, maintenance of hippocampal morphologic and functional plasticity, and preventing HPA axis dysfunction, may account for the profound molecular and cellular mechanism underlying the antidepressant-like effect of YL-IPA08.
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| http://dx.doi.org/10.1016/j.neuropharm.2016.11.004 | DOI Listing |
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YL-IPA08, exerting rapid antidepressant-like and anxiolytic-like effects on behaviors by translocator protein (TSPO) mediation, is a novel compound that has been discovered and developed at our institute. Fit-for-purpose pharmacokinetic properties is urgently needed to be discovered as early as possible for a new compound. YL-IPA08 exhibited low bioavailability (∼6%) during the preliminary pharmacokinetics study in rats after oral administration.
View Article and Find Full Text PDFAntidepressant-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in chronically stressed rats.
Neuropharmacology
February 2017
Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address:
Article Synopsis
- - The study investigates the antidepressant-like effects of YL-IPA08, a new ligand that targets the translocator protein (TSPO), using a rat model of chronic unpredictable stress (CUS) to simulate depression.
- - Results showed that YL-IPA08 improved locomotor activity, increased sucrose preference, and shortened time to eat in stressed rats, indicating reduced depressive-like behaviors.
- - Additionally, YL-IPA08 elevated levels of progesterone and allopregnanolone in key brain areas, reversed damage to neuronal structures, and corrected hormone regulation issues, suggesting its potential effectiveness in treating depression through multiple cellular mechanisms.
Antidepressant-like and anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa).
Neuropharmacology
June 2014
Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, PR China. Electronic address:
It has been demonstrated that the translocator protein (18 kDa) (TSPO) plays an important role in stress-response and stress-related disorders, such as anxiety and depression, by affecting the production of neurosteroids, supporting the potential use of selective TSPO ligands as antidepressant or anxiolytic drugs. N-ethyl-N-(2-pyridinylmethyl)- 2-(3,4-ichlorophenyl)- 7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride (YL-IPA08), a novel TSPO ligand that has been synthesized at our institute, exerted a high affinity for TSPO in a crude mitochondrial fraction prepared from rat cerebellum but exhibited only a negligible affinity for the central benzodiazepine receptor. As expected, YL-IPA08 incubation with the cultured rat astrocyte cells increased the pregnenolone and progesterone concentration from the cultured medium.
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