Love and the immune system

Valentine’s day is a day when we celebrate romantic love (well, some of us tend to) long before the famous greeting card company Hallmark was established. Fittingly, I found the perfect paper to cover for this occasion.

In the past couple of decades it became clear to scientists that there is no such thing as a mental experience that doesn’t have corresponding physical changes. Why should falling in love be any different? Several groups have already found that levels of some chemicals (oxytocin, cortisol, testosterone, nerve growth factor, etc.) change when we fall in love. There might be other changes as well. So Murray et al. (2019) decided to dive right into it and check how the immune system responds to love, if at all.

For two years, the researchers looked at certain markers in the immune system of 47 women aged 20 or so. They drew blood when the women reported to be “not in love (but in a new romantic relationship), newly in love, and out-of-love” (p. 6). Then they sent their samples to their university’s Core to toil over microarrays. Microarray techniques can be quickly summarized thusly: get a bunch of molecules of interest, in this case bits of single-stranded DNA, and stick them on a silicon plate or a glass slide in a specific order. Then you run your sample over it and what sticks, sticks, what not, not. Remember that DNA loves to be double stranded, so any single strand will stick to their counterpart, called complementary DNA. You put some fluorescent dye on your genes of interest and voilà, here you have an array of genes expressed in a certain type of tissue in a certain condition.

Talking about microarrays got me a bit on memory lane. When fMRI started to be a “must” in neuroscience, there followed a period when the science “market” was flooded by “salad” papers. We called them that because there were so many parts of the brain reported as “lit up” in a certain task that it made a veritable “salad of brain parts” out of which it was very difficult to figure out what’s going on. I swear that now that the fMRI field matured a bit and learned how to correct for multiple comparisons as well as to use some other fancy stats, the place of honor in the vegetable mix analogy has been relinquished to the ‘-omics’ studies. In other words, a big portion of the whole-genome or transcriptome studies became “salad” studies: too many things show up as statistically significant to make head or tail of it.

However, Murray et al. (2019) made a valiant – and successful – effort to figure out what those up- or down- regulated 61 gene transcripts in the immune system cells of 17 women falling in love actually mean. There’s quite a bit I am leaving out but, in a nutshell, love upregulated (that is “increased”) the expressions of genes involved in the innate immunity to viruses, presumably to facilitate sexual reproduction, the authors say.

The paper is well written and the authors graciously remind us that there are some limitations to the study. Nevertheless, this is another fine addition to the unbelievably fast growing body of knowledge regarding human body and behavior.

Shame that this research was done only with women. I would have loved to see how men’s immune systems respond to falling in love.

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REFERENCE: Murray DR, Haselton MG, Fales M, & Cole SW. (Feb 2019, Epub 2 Oct 2018). Falling in love is associated with immune system gene regulation. Psychoneuroendocrinology, Vol. 100, Pg. 120-126. doi: 10.1016/j.psyneuen.2018.09.043. PMID: 30299259, PMCID: PMC6333523 [Available on 2020-02-01], DOI: 10.1016/j.psyneuen.2018.09.043 ARTICLE

FYI: PMC6333523 [Available on 2020-02-01] means that the fulltext will be available for free to the public one year after the publication on the US governmental website PubMed (https://www.ncbi.nlm.nih.gov/pubmed/), no matter how much Elsevier will charge for it. Always, always, check the PMC library (https://www.ncbi.nlm.nih.gov/pmc/) on PubMed to see if a paper you saw in Nature or Elsevier is for free there because more often than you’d think it is.

PubMed = the U.S. National Institutes of Health’s National Library of Medicine (NIH/NLM), comprising of “more than 29 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites” .

PMC = “PubMed Central® (PMC) is a free fulltext archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health’s National Library of Medicine (NIH/NLM)” with a whooping fulltext library of over 5 million papers and growing rapidly. Love PubMed!

By Neuronicus, 14 February 2019

Aging and its 11 hippocampal genes

Aging is being quite extensively studied these days and here is another advance in the field. Pardo et al. (2017) looked at what happens in the hippocampus of 2-months old (young) and 28-months old (old) female rats. Hippocampus is a seahorse shaped structure no more than 7 cm in length and 4 g in weight situated at the level of your temples, deep in the brain, and absolutely necessary for memory.

First the researchers tested the rats in a classical maze test (Barnes maze) designed to assess their spatial memory performance. Not surprisingly, the old performed worse than the young.

Then, they dissected the hippocampi and looked at neurogenesis and they saw that the young rats had more newborn neurons than the old. Also, the old rats had more reactive microglia, a sign of inflammation. Microglia are small cells in the brain that are not neurons but serve very important functions.

After that, the researchers looked at the hippocampal transcriptome, meaning they looked at what proteins are being expressed there (I know, transcription is not translation, but the general assumption of transcriptome studies is that the amount of protein X corresponds to the amount of the RNA X). They found 210 genes that were differentially expressed in the old, 81 were upregulated and 129 were downregulated. Most of these genes are to be found in human too, 170 to be exact.

But after looking at male versus female data, at human and mouse aging data, the authors came up with 11 genes that are de-regulated (7 up- and 4 down-) in the aging hippocampus, regardless of species or gender. These genes are involved in the immune response to inflammation. More detailed, immune system activates microglia, which stays activated and this “prolonged microglial activation leads to the release of pro-inflammatory cytokines that exacerbate neuroinflammation, contributing to neuronal loss and impairment of cognitive function” (p. 17). Moreover, these 11 genes have been associated with neurodegenerative diseases and brain cancers.

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These are the 11 genes: C3 (up), Cd74  (up), Cd4 (up), Gpr183 (up), Clec7a (up), Gpr34 (down), Gapt (down), Itgam (down), Itgb2 (up), Tyrobp (up), Pld4 (down).”Up” and “down” indicate the direction of deregulation: upregulation or downregulation.

I wish the above sentence was as explicitly stated in the paper as I wrote it so I don’t have to comb through their supplemental Excel files to figure it out. Other than that, good paper, good work. Gets us closer to unraveling and maybe undoing some of the burdens of aging, because, as the actress Bette Davis said, “growing old isn’t for the sissies”.

Reference: Pardo J, Abba MC, Lacunza E, Francelle L, Morel GR, Outeiro TF, Goya RG. (13 Jan 2017, Epub ahead of print). Identification of a conserved gene signature associated with an exacerbated inflammatory environment in the hippocampus of aging rats. Hippocampus, doi: 10.1002/hipo.22703. ARTICLE

By Neuronicus, 25 January 2017

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The song of a fly… the courtship of another

Drosophila melanogaster image illustrating sexual dimorphism and mating behavior. Credit: TheAlphaWolf (Wikimedia Commons)
Drosophila melanogaster image illustrating sexual dimorphism and mating behavior. Credit: TheAlphaWolf (Wikimedia Commons)

Did you know that flies sing? True to the dictum that I just made up – ‘where is song, there is lust’ – it turns out not only that flies can sing, but they even have courtship songs! Granted, since they don’t have a larynx, the male flies sing by vibrating their wings in a certain way, which is unique to each fly species, and females listen with the feather-looking bit on top of their antennae, called arista. The behavior has generated enough research that a fairly hefty review about it has been published two years ago in Nature Reviews Neuroscience, pointing to a gene central to the male courtship circuitry and expressed only in the fly’s neurons, the fru gene (I bet it was called that way because when you make mutants you get fru/fru …).

Zhou et al. (2015) used a series of complicated experiments to successively activate or inhibit the neurons which express the fru gene, in order to identify the neural circuitry underlying hearing and processing the courtship songs. This circuitry is different in males and females, which makes sense since the serenading male expects different behaviors from his audience, depending on their sex; the listening males hurry to compete for the intended female and the females slow down and… listen carefully. Mind wondering: if I was the one serenading, wouldn’t I want to drive away the competitors, instead of drawing them in towards the object of my desire? Perhaps I want the competitors to also engage in courtship behavior so I can show off my wing vibrating prowess… Anyway, digression aside, in addition to figuring out which neuron does what, the authors managed to elicit courtship behavior in the listening males by optogenetically stimulating the 3rd and 4th order neurons in the newly identified circuit.

Besides being strangely interesting in itself, the research fills a gap in the understanding how courtship behavior is recognized, at least in fruit flies, which may be very useful information for other species as well, humans included.

Reference: Zhou, C., Franconville, R., Vaughan, A. G., Robinett, C. C., Jayaraman, V., & Baker, B. S. (21 September 2015). Central neural circuitry mediating courtship song perception in male Drosophila. Elife, 4:1-15. doi: 10.7554/eLife.08477. Article + FREE PDF

For the interested specialist, the MATLAB source code for analyzing calcium-imaging data can be found here.

By Neuronicus, 24 September 2015