3 Minute 3Rs

You’re listening to the September episode of 3 Minute 3Rs.

The papers behind the pod:

1.       Multicellular 3D Neurovascular Unit Model for Assessing Hypoxia and Neuroinflammation Induced Blood-Brain Barrier Dysfunction. Scientific Reports https://www.nature.com/articles/s41598-020-66487-8

2.      Automated and rapid self-report of nociception in transgenic mice. Scientific Reports https://www.nature.com/articles/s41598-020-70028-8

3.      Zebrafish as an alternative animal model in human and animal vaccination research Laboratory Animal Research https://labanimres.biomedcentral.com/articles/10.1186/s42826-020-00042-4

Transcript:

It’s the 3rd Thursday of September, and you’re listening to 3 Minute 3Rs, your monthly recap of efforts to replace, reduce, and refine the use of animals in research. This month, we’ll let mice do the talking and hear about using zebrafish to study vaccines. But let’s start with an update on an organoid.

[NC3Rs] Back in 2018, Goodwell Nzou and colleagues from the Wake Forest Institute for Regenerative Medicine in the United States published their microscopic replica of the human brain, formed from the six major neural cell types including neurons and immune cells. This miniature organ, or organoid, not only promoted the formation of a blood brain barrier, the resultant barrier was also functional.

Fast forward to today, and in a publication in Scientific Reports, Nzou et al have demonstrated how this platform could be used in drug screening. Disruption of the blood brain barrier in neurological disorders, such as ischaemic stroke, is common, exacerbating the injury to the brain and contributing to cognitive impairment. By culturing the organoid in hypoxic conditions, replicating low oxygen resultant from a stroke, they were able to show expression of proteins critical for blood brain barrier function were altered, leaving the barrier disrupted and leaky. 

Inducing ischaemic stroke in rodents is associated with significant welfare concerns, including death, weight loss, sensorimotor defects and seizures. Using organoids can replace some of these experiments in disease modelling and therapeutic development, so this new publication could have big implications for the 3Rs. You can find out more by following the link in the description.

[Lab Animal] Next, some self-reporting of pain.  Mice are inevitably used to study the mechanisms underlying nociception, with the goal of better understanding pain in people and how to treat it. Many studies rely on reflex assays, but interpreting these can be subjective and there’s uncertainty about what the mice are feeling and reacting to. This can limit study of the neuronal pathways involved and the affective components of pain perception.

A new study in the journal Scientific Reports presents an assay in which transgenic mice learn to self-report exposure to a nociceptive stimulus. The mice, head fixed in the current study, were trained to lick a water spout in response to optogenetic stimulation of heat-sensing neurons in their hind paw. The authors suggest that self-reporting may provide a quicker read-out of nociception that may better reflect the animals’ affective state, and hopefully help make results with the mice more translationally relevant.

And we’ll finish with a topic that’s likely on many of our minds: vaccines.

[NA3RsC] You are probably aware of the recent push to develop a vaccine for COVID-19. Before these vaccines are given to people...