18. Andreea Furdui

The Role of Somatostatin-Expressing Cells in Opioid-Induced Respiratory Depression.

7 Comments

  • Richard Horner says:

    Nice poster Andreea. Good luck for the MSc to PhD transfer next week

  • Tereza Martinu says:

    Great work, Andrea. I am making sure that I understand the difference between SST-MOR-/- and MOR-/- mice. SST-MOR-/- have MOR deficiency only in somatostatin-expressing cells, while MOR-/- are somatic MOR knockouts (in all cells) – is that right? It seems that MOR-/- have less of a response to fentanyl than SST-MOR-/- mice in figure 2b, right? Does that mean that MOR in non-somatostatin-expressing cells plays a role?

    • Andreea Furdui says:

      Correct! MOR-/- mice have MORs knocked out in all cells that would normally express them, whereas SST-MOR-/- mice lack MORs only in cells that also express somatostatin (non-specific vs cell type-specific knockout, respectively). The cells that express somatostatin in the preBotzinger Complex are important for breathing so we wanted to see what their role is in respiratory depression by opioids. In regards to your second question, MORs are the target of opioids such as fentanyl and morphine and activation of these receptors does lead to respiratory depression, so it’s not unexpected to see that when we knock out all MORs there is less of a response to fentanyl. Based on our results, when we do a cell-specific knockout where only SST-expressing cells lack MORs but all other cells still express them, we still see respiratory depression in response to fentanyl, which suggests that MORs in SST-cells specifically are not required for this process. Thanks for your questions!

  • Adele Coriati says:

    Well done on the project Andrea! Following up on Dr Martinu’s comment, would you know what might explain the delay in response in the MOR-/- when injected with fentanyl?

    • Andreea Furdui says:

      Yes, part of this experiment involves capturing video recordings in order to examine the behaviour of our mice in response to fentanyl. There is some evidence that the degree to which the preBotzinger Complex is involved in breathing depends on arousal sate (awake, asleep, etc) so we wanted to see if there are differences in respiratory depression in our strains of mice based on these states. We are currently analyzing this data; however, our preliminary analysis suggests that wild type and SST-MOR-/- mice experience an increase in locomotion following fentanyl injection and are awake during this period, while MOR-/- have a reduced response to fentanyl and don’t have this same locomotive response. Instead the MOR-/- settle down after 5-10 min. into an inactive non-locomotive state which corresponds to the decreased respiratory rate seen in Figure 2b. So in summary, it appears to be a change in behaviour rather than an effect of fentanyl in the MOR-/- mice. Thank you for your question!

  • Andreea Furdui says:

    @Richard Horner Thank you!

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