Men Trigger Stress in Mice
Of course I tweeted Hiring opportunities for #StemWomen when I saw the headlines. Jokes ensued. Could the gender of the researcher really have a noticeable effect on experimental outcomes with animals? This was a #journalclub worthy post, so here goes.
Don’t Stress Me Bro: Experimenters from a Montreal-based lab noticed anecdotally, that pain response in mice was less in human presence. Blunting of pain happens not when one has warm and fuzzy feelings, it turns out, but under stress. So an experiment was set up to measure pain response using a highly sensitive measure known as “mouse grimace scale”. Mice were anesthetized and injected in the leg with some yeast cell wall extract (zymosan) known to cause inflammatory pain. Their expressions were recorded by video and scored by a “blinded” observer, either in an empty room, or in the presence of a male or female lab person sitting quietly half a meter away. The grimace response was lower when a male was in the room. It didn’t matter if a female was present or not. Both male and female mice showed statistically significant response to guys, but the effect was larger in female mice!
Bros and BO: Rodents have a keen sense of smell, so the researchers tested if a T-shirt worn overnight by a male and place 0.5 m away would have the same effect. Yep, male BO was stressful, but female smells were ignored (oddly, the female shirt also cancelled out the effect of the male shirt. Why?). Males produce androgens and these are conserved in other animals. Pure samples of these chemicals had the same effect. Male cats and dogs had the same effect. So the researchers were on to something real.
Stress induced analgesia is an evolutionary adaptation thought to protect us in times of fight or flight. In the figure shown, panel a shows a rise in rodent stress hormone (corticosterone) levels by the mere presence of males, or their T-shirts. The stress response was similar to other unpleasant experiences such as being confined in a closed space or forced to swim! Actually, the animals were sh** scared (to be more scientific, they deposited more fecal boli; panel b). They became hot and bothered, as seen by the rise in body temperature (panel c).
What convinced me were the data in panel d. When triggered, pain-sensing neurons are known to produce a protein known as Fos. As you can see, Fos production after zymosan injection was significantly lowered by male presence. The rest of the paper showed that the effect could be blocked using drugs that reversed known opioid and non-opioid pain pathways. The study also examined other behavioral indicators of pain and stress and confirmed these findings.
Cause for Paws Pause: I can see that this gender-specific effect would add noise to data, but is it large enough to skew the overall conclusion? It is impressive that the effect could be mimicked by androgens, but they were used at very high, non-natural concentrations. Also, chemical effects ought to show a “dose response” and these were found to be weak. Still, I found the results in the attached figure to be convincing; how about you? Also, it gave me an excuse to post the cute mouse image.
REF: R.E. Sorge et al., “Olfactory exposure to males, including men, causes stress and related analgesia in rodents,” Nature Methods, doi:10.1038/nmeth.2935, 2014. http://goo.gl/9qpNh9
forse la chimica dei maschi , nel caso specifico uomini e’ la chimica del capo branco ,
maybe the chemistry of the males, in this case men is the chemistry of the leader of the pack, more reassuring.
gaetano pollio yes, the chemistry of males is involved (the chemicals are called androgens). Unfortunately, not reassuring but stressing 🙂
It really is an interesting finding. I’m genuinely surprised, which is usually the most interesting result of research one can hope for! 😀
On a personal, I-know-anecdote-isn’t-data-but-still note, I’ve kept rats, and the males were almost universally easier to handle, more social, and less prone to bitery and such. I chalked it up to just one of those sexually dimorphic things and did not think on it further. I’m kind of bummed at the thought that just my presence was stressing the females. I really tried to take good care of all of them!
No wonder why the secretary at work gets mad when I walk into her office.
Robert Moser anecdotes got this research started too -and it’s just the sort of thing lab personnel would notice, so it rings true. Your observation on a more pronounced effect on females is borne out by this study! Perhaps you could have borrowed a T-shirt from a female to calm them down. Now that’s a weird pick up line, but you could claim it was backed by science quite truthfully 😀
So many jokes. But I’ll be kind.
Mike Clancy and Jesse H , of course the follow up question for research is: we know the mice are stressed, what about women? 🙂
Pam Adger I know, right? 😀
Agreed, Pam Adger . Kind of takes the fun out of innuendo when it writes itself! 😀
I like to think I have a calming effect on the people around me, women & men alike, but I can’t remember a time I’ve been somewhere without being there.
Thinking about it further, I wonder if we’ll notice unexpected secondary effects if more people start using telepresence (and pheromone-free) robots to interact at work, conferences, and the like.
Men stress everybody 😉
Maria Soledad Velastin , based on this research, each other too 🙂
I love your silver lining rewrite!
Robert Moser there’s bound to be some positive effect from pheromones and other volatiles we give off!
John Bump you mean the tweet? 🙂
There is that recent paper that suggested certain pro-social behaviors are promoted by testosterone. I fully admit to feeling somewhat heartened by that. 🙂
The ScienceDaily tl;dr:
Great summary! I wish all science was as easily digested, thorough and entertaining as yours.
Heroic altruism? Wow, that’s a good save Robert Moser 🙂 I’ll have to give the paper a read, thanks.
Alan Truly , thank you. I want to be able to convey how the experiments were done, and what the data look like, so people can see for themselves.
Gnotic Pasta Here’s your new pick up line: A brief exposure to you would be the equivalent to a swim (panel a) and therefore a good exercise substitute 😀
Well, I had one for Robert Moser but it was better suited for you. Ask a female to leave her T-shirt behind to cancel out your stress -oh, it has to be freshly worn 😉
Uh oh, busted.
I read many places that pheromones in small insects trigger a response in various cases.
I wonder if the chemical signal is more critical in shaping our responses if they are triggered by involuntary reactions.
Our cooperation with people surrounding us is already biased based on chemical signals we received before a single word or a visual contact is made.
Agree, mandar khadilkar . These unseen signals may well shape our behavior just as they do for insects. There are pheromone-based perfumes on the market. Should experiment with them in the name of science 😉
🙂 Ha, Ha!
Darn it. You beat me to it Rajini Rao. This has been going around and I was going to look at the hype vs. science factor. You did a tremendous job as usual. Two things that probably have more negative influence is whether the handler is comfortable with animals or not. Rodents can easily sense if you are afraid to handle them. The second thing, for rats especially, is that they can sense/smell death. If you have a carcass nearby, you will certainly bias
screw upyour experiment.
Wait, Rajini Rao, are you telling me I could get a woman out of her shirt if I find myself a few white mice? Science works in mysterious ways…
Chad Haney I couldn’t find much hype in the actual article..perhaps because it was written for Nature Methods. It came across as quite pragmatic and reasonable. Let me know if you see any #sciencemediahype relating to this story.
Olaf Fichtner let me know if it works. On the other hand, if it doesn’t… 😉
Chad Haney the fear factor is very real. It’s actually quite sad because the mothers can sense when you come to take the pups away 😦
Wait! You’re not putting me into the placebo group, are you?
Of course not, Olaf Fichtner 😉
The only way to find out is after you get slapped in the face
Science for topless scientists? Is that where this winds up?
On a vaguely rational note, I find it really interesting that the Fos numbers were almost identical for females and female shirts but skewed higher for male shirts above males.
Hard to know how meaningful those small differences were, Bill Collins . Some of those values were spread out quite a bit. It’s also the reading that is most complex to make (invasive, lots of processing).
Thanks for the clarification. Now someone needs to do a study on mice taking off their shirts stressing elephants.
Truth is stranger than fiction: To feel relax one must be stressed?
My very presence frightens mice. Yea, witness my power, ye mighty, and tremble.
This also explains the looks I get when I take off my shirt in public and hand it to a total stranger. Before reading this I thought I was just weird.
Can’t stop laughing Rajini Rao to comment, maybe I will come back later when more composed. Great post!
It is a very interesting and important study. I would like to see it reproduced in other labs for other assays.
I like the fact that the researchers were paying attention to unexplained (at the time) variation.
I enjoyed reading the post too.
nice post madam Rajini Rao
Thanks mice for the compliments(though Rajini Rao emphisizes on stressful NOT reassuring), but I would prefer female nurses when I go to hospitals.
But it’s a rat in the picture 😉
The findings research on the olfactory response of rodents was quite interesting. Particularly intriguing is the fact that the observations might be dependent on the gender of the lab person. I think it’s quite mysterious.
After reading this, I’m reminded of a movie called “of Mice and Men” starring John Malkovitch and another actor. It’s a really beautiful and emotionally moving film.
Adit Morey, you just really hurt Gary Sinise…
add to it that most men working on mice biology also choose male mice, wonder what happens when male humans work with female mice.. !
Rats!! I goofed. Jonas Aurelius Blom , good catch 🙂
chaitanya athale the effect of male researchers on female mice was even more pronounced, according to this paper (I think the data are buried in supplement, but they do mention it in the results).
John Stroncheck to clarify, the poor mice are not actually feeling relaxed when they feel less pain. Stress temporarily suspends a lot of physiological distractions to give the animal the best chance of dealing with a potentially harmful situation.
Olaf Fichtner, thanks for the information! :)… apologies to Gary Sinise.
:-P… he also acted in “Forrest Gump”. Great movie.
Yeah, I was pretty disappointed to read this too, but it’s really kind of mixed. Sometimes it’s kind of necessary to ignore pain in order to undertake action necessary for survival or advancement, right?
I don’t like the idea that I have no control over the effect I have on other creatures, though.
Huh. This study showed that women self-reported feeling less tense and more relaxed when exposed to male pheromones. That isn’t exactly a direct contradiction, but there’s probably something complex going on here. http://www.nature.com/news/2003/030527/full/news030527-2.html
Jay Gischer , thanks for the link. I’ve downloaded the paper and I will report back on the findings later this evening after I’ve had a chance to read it. A quick glance shows that most of the paper is on measuring hormone levels (luteinizing hormone, LH) in females, the “relax/tense” scale was thrown in at the end of the paper and is based on self-assessment of mood on a 1-7 scale (with small differences of 0.5).
Yeah, the self-assessment makes the result weaker, I think. And “less tense” isn’t the same thing as “not stressed” either. I mean, riding a roller coaster is stressful, right?
Raphael Williams the T-shirts were worn overnight, then bagged in plastic and exposed to mice the next day. After a while, they lost their effect. T-shirts would be a better garment to soak up odorants and to sleep in, compared to lab coats. But, your raise a great point about lab coats! Assuming everyone wears lab coats, these diffusible compounds must escape them to reach the mice. Or perhaps they are saturated with the odorants over time, since lab coats don’t get laundered regularly.
since lab coats don’t get laundered regularly.
I don’t mind wearing a labcoat. I do miss working in the hospital where laundry was less of an issue.
I have no idea when/where/if lab coats are laundered in my lab. I’m not going to admit here whether we use them or not 😉
good …. but Rajini, I have to say, as a lab mouse, I always feel, my pain response goes up when there is girl in the lab and not when a man around. More the girls around, more the pain I experience, this includes, neurological, muscular and mental pains too … 🙂
PS: I mean it, really !
It’s good to hear the mouse’s point of view. That was missing from the paper, thanks! 😀
Perhaps, I may have to ask the authors to include me in their study subject and reinvent the differential gene expression pattern profile 😀
Raphael Williams good question, here is the answer: “Changing the sex of the technician providing animal husbandry did not alter results (Supplementary Fig. 3), nor did changing the sex of the person administering zymosan (Supplementary Fig. 4)”.
Interestingly, they go out of their way to state that these are not pheromone effects but rather olfactory stimuli caused by chemically unrelated scents that affect the hypothalamus. I’m not sure what the chemical difference between a male pheromone and androgen is, to be honest.
V R Swamy volunteer mice are always appreciated! There may be some loss of brain material for testing differential gene expression, but it’s all for the cause of science! 🙂
Adit Morey , I love literary connections, so thank you for the reference to Steinbeck’s novel (and movie). Of Mice and Men was indeed the title chosen by some journalists who reported on this story. The origin of this phrase is the poem of Robert Burns, which goes “the best laid plans of mice and men, often go awry” (although he used ye olde English) 🙂
The ending of that phrase, by the way, in Middle English, which I once knew better, was “aft gang agley”. Today’s English is not the same, although it’s a clear descendant.
Bill Collins , I can’t decide if that phrase sounds romantic or awkward 🙂
I leave that to the awkward and/or romantic moments between men and their mice, or mice and their men. 😉
Haha! Beautiful or agley..it’s in the eye of the beholder.
Thanks Proff. Rajini Rao for information about the origin of the phrase “of mice and men”!:)… I myself like reading too, though I mostly read popular fiction novels like those by John Grisham and Jeffrey Archer. 🙂
Amazing rodent olfaction:
There are currently 66 countries and 7 territories around the world that are affected by landmines and explosive remnants of war that pose a structural barrier to development and economic growth. APOPO has trained innovative Mine Detection Rats (MDRs), leading to more efficient mine action work.
The need for faster TB diagnosis in overpopulated high burden cities is paramount. APOPO is working towards eradicating TB in Sub-Saharan Africa by training locally available rats to evaluate sputum samples more swiftly and efficiently. One rat can evaluate in ten minutes more samples than a lab technician can do in one day.
Thanks, Matt Kuenzel . Odors are detected by olfactory receptors. For a sense of comparison, there are ~100 olf genes in fish, ~340 in humans and >1,000 in rodents!
P.S. the ability to detect TB is remarkable! I had not heard that, thanks!
>1000 in rodents. The evolutionary pressure on rodents looks very high on specialized sense of smell.
Rodents fascinate me. I had a gerbil and a rabbit (as well as a dog) for pets when I was a child.
Now I have a new reason to stay out of the vivarium:-)
Timothy Reinhardt , excellent excuse. Men should totally own this, as Michael Verona suggests 🙂 Did I tell you all my attempts to get out of teaching “dog lab” in medical school? First I claimed squeamishness, then explained that I was a vegetarian and finally (to my everlasting shame!) hinted about being a hindu. Now, the dog lab is a virtual exercise.
That’s OK Rajini Rao I turned down a postdoc at JHU because I didn’t want to do cat brain surgery everyday. I also turned down a postdoc at Yale because I didn’t want to be in a lab that does cardiovascular research on dogs and everyone was expected to help.
Now the Onion has has polled the ordinary person on the street about this important research 😉 http://www.theonion.com/articles/study-lab-mice-stressed-out-by-male-scientists,35920/
Two for Tee discount on a Chamomile tea with me in a calming Tee combo? Soon to be on eBay.