Ma, Rong; Kutchy, Naseer A.; Hu, Guoku published the artcile< Astrocyte-Derived Extracellular Vesicle-Mediated Activation of Primary Ciliary Signaling Contributes to the Development of Morphine Tolerance>, Reference of 6823-69-4, the main research area is astrocyte extracellular vesicle primary ciliary signaling morphine; Astrocyte; Extracellular vesicle; Morphine tolerance; Primary cilia; Sonic hedgehog.
Morphine is used extensively in the clin. setting owing to its beneficial effects, such as pain relief; its therapeutic utility is limited because the prolonged use of morphine often results in tolerance and addiction. Astrocytes in the brain are a direct target of morphine action and play an essential role in the development of morphine tolerance. Primary cilia and the cilia-mediated sonic hedgehog (SHH) signaling pathways have been shown to play a role in drug resistance and morphine tolerance, resp. Extracellular vesicles (EVs) play important roles as cargo-carrying vesicles mediating communication among cells and tissues. C57BL/6N mice were administered morphine for 8 days to develop tolerance, which was determined using the tail-flick and hot plate assays. EVs were separated from astrocyte-conditioned media using either size exclusion chromatog. or ultracentrifugation approaches, followed by characterization of EVs using nanoparticle tracking anal. for EV size distribution and number, Western blotting for EV markers, and electron microscopy for EV morphol. Astrocytes were treated with EVs for 24 h, followed by assessing primary cilia by fluorescent immunostaining for primary cilia markers (ARL13B and acetylated tubulin). Morphine-tolerant mice exhibited an increase in primary cilia length and percentage of ciliated astrocytes. The levels of SHH protein were upregulated in morphine-stimulated astrocyte-derived EVs. SHH on morphine-stimulated astrocyte-derived EVs activated SHH signaling in astrocytes through primary cilia. Our in vivo study demonstrated that inhibition of either EV release or primary cilia prevents morphine tolerance in mice. EV-mediated primary ciliogenesis contributes to the development of morphine tolerance.
Biological Psychiatry published new progress about ADP ribosylation factor-like protein ARL13B Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Reference of 6823-69-4.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem