As part of our remit of working with beasties, it is important for us to discuss animal work.
Working on EAE is becoming a dying art….I have recently met a few colleagues who have said their ethical boards have stopped them working on EAE. The Home Orifice in the UK, who control animal experiments in the UK has EAE within its sights and so we are living on borrowed time.
Indeed in Europe you now have to integrate the 3Rs (reading, righting and rithmatic) of animal use into animal work, you have to read about the problems and as some bright spark thinks that doing pain studies in EAE creates a new avenue for research when (a) they are wasting their time as the pain (e.g. enhanced sensitivity before disease develops) they think they are looking at, has very little to do with the neuropathic pain that occurs in MS and (b) making alarm bells for the ethical review panels because now they not only think that EAE stops animals moving, they now think it is painful and so (c) more determined to stop people doing EAE studies. (d) It makes it impossible to get money to do animal work in the UK and the work goes east or westwards where they don’t care as much about the furry beasties…..The horror stories that I reject from publication come from the Far East. (e) Doesn’t it make you happy that GSK (UK based pharma) moved their neuroscience research from UK to China. It was cheaper and less regulated.
Now you have to rite loads of proposals to get anywhere as people aren’t interested in animal work. You have to do the rithmatic to determine whether it is worth doing it or not.
Yep I know the 3Rs (Reduction, refinement, replacement) mean something else it is all about stopping animal use or refining what is done. Some will argue that doing chemical demyelinating studies is more refined and less stressful to the animals than EAE. So just as the do-gooders have got it in for EAE, the chemical demylination brigade is being sent a nail for its coffin. Now they are having to worry about the heart problems they are causing and never knew about. You often only know if there is a problem if you look for the problem. So in this study the cardiac risk that we were not thinking about now becomes an animal issue and the severity of the procedure may now increase.
A novel role of cardiac inwardly rectifying potassium channels explaining autonomic cardiovascular dysfunctions in a cuprizone-induced mouse model of multiple sclerosis. Akyuz E, Villa C.Auton Neurosci. 2020;225:102647
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), believed to have an autoimmune etiology. MS patients showed an increased cardiovascular (CV) risk probably related to an impairment in the autonomic control of CV functions, but the underlying molecular mechanisms are not completely elucidated. Inwardly-rectifying potassium (Kir) channels play a key role in cardiac excitability by contributing to the repolarization phase of action potential and were recently identified as target of the autoantibody response in MS patients. Therefore, we investigated the role of cardiac Kir channels in the CV dysfunctions occurring in MS. Cardiac functions were evaluated by electrocardiographic recordings (ECG) in cuprizone-fed C57BL/6 mice, a classic demyelination animal model. Gene expression profiling of cardiac Kir2.2, Kir4.1 and Kir6.2 channels was performed using real-time PCR in mice. Cuprizone-induced mouse model was confirmed by immunohistochemistry analysis showing demyelination in the corpus callosum. ECG recordings from mice showed an increase of the heart rate in cuprizone-treated mice as compared with the controls. Significant increased relative expression levels of Kcnj11 and Kcnj12, encoding for Kir6.2 and Kir2.2 channels respectively, were observed in mouse heart tissue, whereas no differences were found in mRNA levels of Kir4.1 channel as compared with controls. For the first time, these findings provided valuable insights into the potential role of Kir channels in cardiac problems associated with MS.
Now cuprizone cause heart problems, and problems for remyelination researchers.