98%
921
2 minutes
20
The study focuses on the anxiolytic potential of chalcone (2E,4E)-1-(2-hydroxyphenyl)-5-phenylpenta-2,4-dien-1-one (CHALCNM) in adult zebrafish. Successfully synthesized in 58 % yield, CHALCNM demonstrated no toxicity after 96 h of exposure. In behavioral tests, CHALCNM (40 mg/kg) reduced locomotor activity and promoted less anxious behavior in zebrafish, confirmed by increased permanence in the light zone of the aquarium. Flumazenil reversed its anxiolytic effect, indicating interaction with GABAA receptors. Furthermore, CHALCNM (4 and 20 mg/kg) preserved zebrafish memory in inhibitory avoidance tests. Virtual screening and ADMET profile studies suggest high oral bioavailability, access to the CNS, favored by low topological polarity (TPSA≤75 Å) and low incidence of hepatotoxicity, standing out as a promising pharmacological agent against the GABAergic system. In molecular coupling, CHALCNM demonstrated superior affinity to diazepam for the GABAA receptor. These results reinforce the therapeutic potential of CHALCNM in the treatment of anxiety, highlighting its possible future clinical application.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/cbdv.202400935 | DOI Listing |
J Neurosci Methods
September 2025
Department of Biosciences and Bioinformatics, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, China; Suzhou Key Laboratory on Neurobiology and Cell Signaling, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, China.
Background: Affective disorders represent a major global health burden. Animal models are widely used for modeling brain disorders and neuroactive drug discovery. A novel powerful tool in translational neuroscience research, zebrafish provide multiple behavioral assays relevant to anxiety-like and depression-related conditions (including despair-like behavior, a common feature in depression).
View Article and Find Full Text PDFJ Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
Korean J Anesthesiol
September 2025
Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15588, the Republic of Korea.
Background: Despite the well-known effects of elevated bilirubin in neonates, its neurotoxic potential in adults remains uncertain. In perioperative and hepatic disease contexts, transient bilirubin elevations are common; however, their direct contribution to cognitive dysfunction has not been clearly established. This study aimed to determine whether transient bilirubin elevation alone can impair cognition and disrupt blood-brain barrier (BBB) function in adult zebrafish, and to compare these effects with those of liver injury.
View Article and Find Full Text PDFStrategies to stimulate the regeneration of neurons in the adult central nervous system can offer universal solutions for neurodegenerative diseases. Taking lessons from naturally regenerating species, such as the zebrafish, we have previously shown that vector-mediated expression of proneural transcription factors can stimulate neurogenesis from the resident Müller glia (MG) population in the adult mouse retina, both and . To bring this closer to translation, we now show that vector-mediated expression of the proneural transcription factor ASCL1 can reprogram adult macaque MG into functional neurons.
View Article and Find Full Text PDFCell Mol Life Sci
September 2025
Key Laboratory of Marine Drugs (Ocean University of China), Chinese Ministry of Education, and School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
The Wnt/β-catenin signaling pathway plays key roles in development and adult tissue homeostasis by controlling cell proliferation and cell fate decisions. TCF/LEF transcription factors play a pivotal role in this pathway, acting as repressors by recruiting co-repressors in the absence of Wnt signals, and as activators via β-catenin binding in the presence of Wnt signaling. While progress has been made in our understanding of Wnt signaling regulation, the underlying mechanism that regulates the protein stability of the TCF/LEF family is far less clear.
View Article and Find Full Text PDF