I2-Imidazoline Ligand CR4056 Improves Memory, Increases ApoE Expression and Reduces BBB Leakage in 5xFAD Mice

• DOI: 10.3390/ijms23137320
• Publication Date: 2022-07-01T04:21:50Z
• Authors: Bibiana C. Mota; Nathan Ashburner; Laura Abelleira-H...; Liyueyue Liu; Robertas Aleksynas; Lucio Claudio Rovati; Gianfranco Caselli; Magdalena Sastre
• Keywords: Imidazoline receptor; Apolipoprotein E; Leakage (economics)

Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer’s disease (AD). We recently demonstrated the I2-ligand BU224 reversed memory impairments AD transgenic mice and this effect was not because reductions amyloid-β (Aβ) deposition. In study, our aim to determine therapeutic potential powerful analgesic ligand CR4056 5xFAD model AD, since has been proven be safely tolerated humans. Sub-chronic oral administration (30 mg/kg for 10 days) led an improvement recognition 6-month-old mice, but wild-type littermates, without affecting Aβ levels or Our results also revealed a change profile microglia by CR4056, resulting suppression pro-inflammatory activated microglia, increased density astrocytes expression ApoE, which is mainly produced these glial cells. addition, restored fibrinogen extravasation, distribution markers astrocytic end feet blood vessels. Therefore, suggest protects against Aβ-mediated neuroinflammation vascular damage, offers at any stage AD.