To study the profile and regulation of apolipoprotein E (apoE) expression in the CNS, we generated mice in which apoE expression can be detected in vivo with unprecedented sensitivity and resolution. cDNA encoding enhanced green fluorescent protein (EGFP) with a stop codon was inserted by gene targeting into the apoE gene locus (EGFPapoE) immediately after the translation initiation site. Insertion of EGFP into one apoE allele provides a real-time location marker of apoE expression in vivo; the remaining allele is sufficient to maintain normal cellular physiology. In heterozygous EGFPapoE mice, EGFP was highly expressed in hepatocytes and peritoneal macrophages. EGFP was also expressed in brain astrocytes; however some astrocytes (approximately 25%) expressed no EGFP, suggesting that a subset of these cells does not express apoE. EGFP was expressed in <10% of microglia after kainic acid treatment, suggesting that microglia are not a major source of brain apoE. Although hippocampal neurons did not express EGFP under normal conditions, kainic acid treatment induced intense expression of EGFP in injured neurons, demonstrating apoE expression in neurons in response to excitotoxic injury. The neuronal expression was confirmed by in situ hybridization of mouse apoE mRNA and by anti-apoE immunostaining. Smooth muscle cells of large blood vessels and cells surrounding small vessels in the CNS also strongly expressed EGFP, as did cells in the choroid plexus. EGFPapoE reporter mice will be useful for studying the regulation of apoE expression in the CNS and might provide insights into the diverse mechanisms of apoE4-related neurodegeneration.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6674234 | PMC |
http://dx.doi.org/10.1523/JNEUROSCI.5476-05.2006 | DOI Listing |
Anticancer Agents Med Chem
January 2025
Department of Biochemistry, Faculty of Science, Selcuk University, Konya, Turkiye.
Introduction/objective: Plants and their bioactive compounds play a crucial role in the pharmaceutical industry for treating cancer. To date, the cytotoxic and antiproliferative effects of Hypericum perforatum methanol extract on human thyroid cancer cell lines have not been thoroughly explored. The present study aimed to assess the potential anti-cancer effects of HPME on human thyroid cancer and investigate its potential therapeutic benefits.
View Article and Find Full Text PDFBrief Bioinform
November 2024
GENYO, Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, PTS Granada, Avenida de la Ilustración 114, Granada 18016, Spain.
Recent advances in single-cell RNA-Sequencing (scRNA-Seq) technologies have revolutionized our ability to gather molecular insights into different phenotypes at the level of individual cells. The analysis of the resulting data poses significant challenges, and proper statistical methods are required to analyze and extract information from scRNA-Seq datasets. Sample classification based on gene expression data has proven effective and valuable for precision medicine applications.
View Article and Find Full Text PDFNeuron
January 2025
Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA. Electronic address:
The complexity of the human brain makes it challenging to understand the molecular mechanisms underlying brain function. Genome-wide association studies have uncovered variants associated with neurological phenotypes. Single-cell transcriptomics have provided descriptions of changes brain cells undergo during disease.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: Thyroid cancer is one of the most common endocrine tumors worldwide, especially among women and the metastatic mechanism of papillary thyroid carcinoma remains poorly understood.
Methods: Thyroid cancer tissue samples were obtained for single-cell RNA-sequencing and spatial transcriptomics, aiming to intratumoral and antimetastatic heterogeneity of advanced PTC. The functions of APOE in PTC cell proliferation and invasion were confirmed through in vivo and in vitro assays.
In Vitro Cell Dev Biol Anim
January 2025
College of Traditional Chinese Medicine, Xinjiang Uygur Autonomous Region, Xinjiang Medical University, Urumqi, 830063, China.
The aim of this study is to assess the impact of Tianxiangdan (TXD) on lipophagy in foam cells and its underlying mechanism in treating atherosclerosis, particularly focusing on its efficacy in lowering blood lipids. In vivo, ApoE-/- atherosclerosis mouse models were established for group intervention. Blood lipid levels of the mice were measured, lipid deposition and autophagy levels in atherosclerotic plaques were assessed, and co-localization of lipid droplets and autophagosomes was examined.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!