Inhaling a bitter tasting solution may help with asthma (don’t try this at home, yet)

bitter - Copy (2)

Asthma is an inflammatory disease of the lungs’ airways. The airway smooth muscle (ASM) expresses a large number of G protein-coupled receptors (GPCRs). The GPCRs are proteins bound to the cell membrane that sense what happens outside the cell and thus signal the cell to engage in appropriate responses. There are many, many types of GPCRs (in the upper hundreds) all over the body. Furthermore, alternative splicing (that is reshuffling parts of the gene that codes for a protein in such a way that you can get several different proteins from the same gene) may produce new types.

In an a effort to characterize the GPCRs in the ASM in the hope of finding an asthma pharmacological target, Einstein et al. (2008) found many more types of these receptors than previously thought, produced mainly by alternative splicing. In a subsequent study, the same group found out that some of these GPCRs are the same GPCRs that are expressed by your tongue in order to taste bitterness (Desphande et al., 2010)! The researchers were not expecting this.

Moreover, the bitter receptors (called TAS2Rs) in the lungs are fully functional, that is they respond to bitter substances like quinine. The response is, surprisingly, that of relaxation of the airways. It’s surprising because the role of bitter receptors in the tongue is to signal avoidance of bitter foods, because they usually contain toxins. So Desphande et al. (2010) (and anyone else in their shoes) would have expected a similar role for the bitter receptors in the lungs: that is, upon smelling something bitter the airways would close to prevent further poisoning. The data proved this expectation to be wrong.

The work so far has been done in isolated human cells. If quinine relaxes the ASM in an Petri dish, would it do so also when the ASM is still attached to its owner? So the researchers gave some bitter inhalants to some mice who had asthma and this treatment DECREASED the airway obstruction in a dose-dependent manner.

Asthma hits 300 million people worldwide and more than a quarter million die of it per year. So this research sparks great hopes for a new treatment direction.

References:

  1. Einstein R, Jordan H, Zhou W, Brenner M, Moses EG, & Liggett SB (1 Apr 2008, Epub 24 Mar 2008). Alternative splicing of the G protein-coupled receptor superfamily in human airway smooth muscle diversifies the complement of receptors. Proceedings of the National Academy of Sciences of the United States of America, 105(13):5230-5. doi: 10.1073/pnas.0801319105. Article | FREE PDF
  1. Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, & Liggett SB. (Nov 2010, Epub 24 Oct 2010). Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nature Medicine, 16(11):1299-304. doi: 10.1038/nm.2237. Article | FREE PDF 

By Neuronicus, 10 March 2016

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Dead salmon engaged in human perspective-taking, uncorrected fMRI study reports

salmon

Subject. One mature Atlantic Salmon (Salmo salar) participated in the fMRI study. The salmon was approximately 18 inches long, weighed 3.8 lbs, and was not alive at the time of scanning.

Task. The task administered to the salmon involved completing an open-ended mentalizing task. The salmon was shown a series of photographs depicting human individuals in social situations with a specified emotional valence. The salmon was asked to determine what emotion the individual in the photo must have been experiencing.”

Before explaining why you read what you just read and if it’s true (it is!), let me tell you that for many people, me included, the imaging studies seem very straightforward compared to, say, immunohistochemistry protocols. I mean, what do you have to do? You stick a human in a big scanner (fMRI, PET, or what-have-you), you start the image acquisition software and then some magic happens and you get pretty pictures of the human brain on your computer associated with some arbitrary numbers. Then you tell the humans to do something and you acquire more images which come with a different set of numbers. Finally, you compare the two sets of numbers and voila!: the neural correlates of whatever. Easy-peasy.

Well, it turns out it’s not so easy-peasy. Those numbers correspond to voxels, something like a pixel only 3D; a voxel is a small cube of brain (with the side of, say, 2 or 3 mm) comprising of hundreds of thousands to millions of brain cells. After this division, depending on your voxel size, you end up with a whooping 40,000 to 130,000 voxels or thereabouts for one brain. So a lot of numbers to compare.

When you do so many comparisons, by chance alone, you will find some that are significant. This is nature’s perverse way to show relationships when there are none and to screw-up a PhD. Those relationships are called false positives and the more comparisons you do, the more likely it is to find something statistically significant. So, in the ’90s, when the problem became very pervasive with the staggering amount of data generated by an fMRI scan, researchers came up with mathematical ways to dodge the problem, called multiple comparisons corrections (like application of the Gaussian Random Field Theory). Unfortunately, even 20 years later one could still find imaging studies with uncorrected results.

To show how important it is to perform that statistical correction, Bennet et al. (2010) did an fMRI study on perspective taking on one subject: a salmon. The subject was dead at the time of scanning. Now you can re-read the above excerpt from the Methods section.

Scroll down a bit to the Results section: “Out of a search volume of 8064 voxels a total of 16 voxels were significant”, p(uncorrected) < 0.001, showing that the salmon was engaging in active perspective-taking.

After the multiple comparisons correction, no voxel lit up, meaning that the salmon was not really imagining what the humans are feeling. Bummer…

The study has been extensively covered by media and I jumped on that wagon too – even if a bit late – because I never tire of this study as it’s absolutely funny and timeless. The authors even received the 2012 IgNobel prize for Neuroscience, as justly deserved. I refrained from fish puns because there are aplenty in the links I provided for you after the Reference. Feel free to come up with your own. Enjoy!

Reference: Bennett, CM, Baird AA, Miller MB & Wolford GL (2010). Neural correlates of interspecies perspective taking in the post-mortem Atlantic Salmon: An argument for multiple comparisons correction. Journal of Serendipitous Unexpected Results, 1, 1–5, presented as poster at the 2009 Human Brain Mapping conference. PDF | Nature cover | Neuroskeptic cover | Scientific American full story

By Neuronicus, 23 November 2015