This is the March episode of 3-Minute 3Rs, brought to you by the North American 3Rs Collaborative (www.na3rsc.org, the NC3Rs (www.nc3rs.org.uk), and Lab Animal (www.nature.com/laban)
The papers behind the pod:
1. Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS. https://bit.ly/2uiF64X
2. A critical evaluation of TRPA1-mediated locomotor behavior in zebrafish as a screening tool for novel anti-nociceptive drug discovery. https://go.nature.com/2Cu7u8C
3. No-touch measurements of vital signs in small conscious animals. https://bit.ly/2WdN5Mw
[NC3Rs] A team led by Dr Rickie Patani has developed a human-derived model of ALS that could bring us a step closer to treating the disease effectively while avoiding the use of animals altogether.
Animal models are widely used to study ALS, also known as motor neurone disease, but current therapies can only slow its progression – and even then, the effect is modest. Instead, Dr Patani's team, based at UCL and the Francis Crick Institute, used human induced pluripotent stem cells to study how ALS causes motor neurones to degenerate. They investigated the molecular processes that lead to the death of motor neurones, which are kickstarted by the loss of a protein called TDP-43 from the cell nucleus. They also discovered that ALS makes astrocytes degenerate too, so they can’t play their usual role in helping motor neurones survive, compounding the effects of the disease. For this work, Dr Patani was awarded the NC3Rs’ International 3Rs Prize earlier this month. The prize is sponsored by GSK and celebrates outstanding 3Rs science every year. Read the paper in Cell Reports or visit the NC3Rs website to learn more about the 3Rs Prize.
[LA] Rodents remain popular for in vivo validation of novel drugs. But screening candidates is costly to do in rodents, which has researchers looking for alternatives to evaluate compounds in a higher throughput manner. Zebrafish are increasingly used for such screening purposes. A new paper from Richard van Rijn’s lab at Purdue published in the journal Scientific Reports evaluates a zebrafish screen for drugs that Transient Receptor Potential A1, or TRPA1. TRPA1 encodes a calcium ion channel and has been shown to be involved in pain perception in rodent models. In zebrafish, activating TRPA1 causes hyperlocomotion, which the researchers hypothesized could be a useful phenotypic readout of drug efficacy. They tested compounds known to activate and inactivate TRPA1 in human cells, mice, and zebrafish larvae and found that the compounds affect all three models in a dose-dependent manner. Evaluation can be somewhat tricky in the zebrafish because they have a second copy of TRPA1 to contend with, but the fish could still help screen initial compounds before researchers take them onward.
[LA] What if you could measure the vital signs of your animals without having to prep or handle them? Engineers at Cornell recently described the use of radio frequency near-field coherent sensing to do just that in a paper published in Science Advances. They developed the technology first for humans, but have now shown its potential for use with small animals in real-time. The technology uses radio waves. These penetrate the body and can be used to detect the motion of internal organs. When the signal is processed, parameters like heart rate and respiration rate can be captured. The system can be wired or wireless, and was shown to work with an anesthetized rat and freely moving hamster, Russian tortoise, and betta fish. There was some variability and further comparisons with existing methods would help clarify the accuracy and robustness of the new system, but near-field coherent sensing could be a promising new way to keep an eye on animal vital signs.