The zebrafish (Danio rerio) is increasingly utilized as a powerful new model organism in neurobehavioral research. Aggression is a common symptom of many CNS disorders, has some genetic determinants and can be modulated pharmacologically in humans and animal model species. Mounting evidence suggests zebrafish as a useful tool to study neurobiology of aggression, and its pharmacological and genetic regulation. Here, we discuss mechanisms of zebrafish aggression and their pharmacological, pharmacogenetic and pharmacogenomic models, as well as recent developments and existing challenges in this field. We also emphasize the growing utility of zebrafish models in translational neuropharmacological research of aggression, fostering future discoveries of potential therapeutic agents for aggressive behavior.
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http://dx.doi.org/10.1016/j.phrs.2019.01.044 | DOI Listing |
Theranostics
January 2025
Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
: The periaqueductal gray (PAG) is a central hub for the regulation of aggression, whereas the circuitry and molecular mechanisms underlying this regulation remain uncharacterized. In this study, we investigate the role of a distinct cell type, -expressing (Tac2) neurons, located in the dorsomedial PAG (dmPAG) and their modulation of aggressive behavior in mice. : We combined activity mapping, Ca recording, chemogenetic and pharmacological manipulation, and a viral-based translating ribosome affinity purification (TRAP) profiling using a mouse resident-intruder model.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Department of Thyroid and Hernia Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou City, Fujian Province 350001, China.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and patients with the BRAF mutation often exhibit aggressive tumor behavior. Here, we identified Arylsulfatase I (ARSI) as a gene whose expression was significantly upregulated in BRAF PTC and was associated with poor prognosis. High ARSI expression correlated with advanced disease stage, BRAF mutation, and worse overall survival in PTC patients.
View Article and Find Full Text PDFSci Transl Med
January 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada.
T-lineage acute lymphoblastic leukemia (ALL) is an aggressive cancer comprising diverse subtypes that are challenging to stratify using conventional immunophenotyping. To gain insights into subset-specific therapeutic vulnerabilities, we performed an integrative multiomics analysis of bone marrow samples from newly diagnosed T cell ALL, early T cell precursor ALL, and T/myeloid mixed phenotype acute leukemia. Leveraging cellular indexing of transcriptomes and epitopes in conjunction with T cell receptor sequencing, we identified a subset of patient samples characterized by activation of inflammatory and stem gene programs.
View Article and Find Full Text PDFNeoplasia
December 2024
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) is characterized by its aggressive nature and dismal prognosis, largely attributed to its unique tumor microenvironment. However, the molecular mechanisms by which tumor-associated macrophages (TAMs) promote PDAC progression, particularly the role of β-catenin signaling in regulating TAM phenotype and function, remain incompletely understood. Initially, we performed comprehensive analyses of RNA-seq and single-cell RNA-seq (scRNA-seq) datasets to investigate OSM and LOXL2 expression patterns in PDAC.
View Article and Find Full Text PDFJCI Insight
December 2024
Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.
Enhancer of Zeste Homologue 2 (EZH2) is part of the Polycomb Repressor Complex 2, which promotes trimethylation of lysine 27 on histone 3 (H3K27me3) and genes repression. EZH2 is overexpressed in many cancers and studies in mice attributed both pro-oncogenic and tumor suppressive functions to EZH2 in pancreatic ductal adenocarcinoma (PDAC). EZH2 deletion enhances de novo KRAS-driven neoplasia following pancreatic injury, while increased EZH2 expression in PDAC patients is correlated to poor prognosis, suggesting a context-dependant effect for EZH2 in PDAC progression.
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