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CNO in drinking water
We frequently get requests regarding protocols for putting CNO in the drinking water for long-term studies. Here is our protocol: 1. Dissolve the CNO in a small volume of DMSO 2. Diluted the dissolved CNO in drinking water (e.g., 5mg/200ml) 3. Give mice with CNO drinking water and protect from light using foil-wrapped bottles 4. The mice will receive 5mg/kg/day CNO (assume that mice weight 30g and consume 6ml water per day) 5. Prepare fresh daily. 6. A small amount of saccharine in the drinking water will mask the slightly bitter taste of CNO
DREADDs cure cancer?
An interesting and provocative paper recently published in Nature Communications: " Modulation of anti-tumor immunity by the brain’s reward system " They conclude: " Activation of the reward system in tumor-bearing mice (Lewis lung carcinoma (LLC) and B16 melanoma) using chemogenetics (DREADDs), resulted in reduced tumor weight. This effect was mediated via the sympathetic nervous system (SNS), manifested by an attenuated noradrenergic input to a major immunological site, the bone marrow. Myeloid derived suppressor cells (MDSCs), which develop in the bone marrow, became less immunosuppressive following reward system activation. By depleting or adoptively transferring the MDSCs, we demonstrated that these cells are both necessary and sufficient to mediate reward system effects on tumor growth. Given the central role of the reward system in positive emotions, these findings introduce a physiological mechanism whereby the patient’s psychological state can impact anti-...
i guess viral expression is evident after 2-3 weeks. How about the upper limit? Something like 2-3 months? Any input would be valuable.
ReplyDeleteThere is a fairly large literature about this in mice as AAV is integrated into the genome. I highlight one paper which shows expression of cargo for at least 12 month (http://online.liebertpub.com/doi/abs/10.1089/10430349950018995 )
ReplyDeleteThe longest we've looked for DREADD expression is 3 months--still expressed at high levels (Urban and Roth, unpublished).
Thank you so much Bryan. Can I have a question regarding CNO effect? How long does it last in mice at 5mg/kg dose ( when injected IP) ? Something like two hours or does it last longer?
ReplyDeletePlease look at the Neuron paper where this was addressed. It is within several minutes (http://www.ncbi.nlm.nih.gov/pubmed/21415127)
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