Written by Jia Yu Geng
Edited by wang multi-fish
Typography water written
As we all know, the same drug, the effect will vary from person to person, and even by gender
Like many drugs that work for men, they may not work for women
Similarly, there will be "gender differences"
in how people respond to drugs.
This sentence may sound like a sick sentence, but it actually happens in
Ketamine (KET) is a powerful and fast-acting anesthetic
Studies in recent years have found that it is also an ideal antidepressant drug that can produce antidepressant effects within a few hours
Most of the researchers in Professor Todd Gould's lab in Professor Todd Gould's lab at the University of Maryland School of Medicine are women
When they repeated the ketamine study in mice, the results often ended in the ineffectiveness of the drug; When male experimenters performed the same operation on mice, the antidepressant effects of ketamine continued to work
To that end, the team also asked other labs in the same field and found the same problem: mice generally showed more fear and nervousness in front of male experimenters; In front of female experimenters, it is much more
relaxed and comfortable.
However, whether this behavioral response of mice to people of different sexes will really affect the results of the experiment is an open question
In addition, ketamine in some human patients, there is also a problem of not being able to produce antidepressant effects
On August 30, 2022, Professor Todd Gould's Lab, together with Associate Professor Scott Thompson et al.
, published a paper titled Experimenters' sex modulates mouse behaviors and neural responses to ketamine via corticotropin in Nature Neuroscience Releasing Factor's research papers
The latest study confirms that the sex of human experimenters influences the behavior and response of mice after ketamine and its bioactive metabolites are administered
The study also found that a specific region in the mouse brain is key to ketamine's efficacy and identified the mechanism behind this action, thus providing a strategy
for human patients who did not respond to ketamine treatment.
Experimental results that cannot be replicated are most likely due to some unknown experimental variables that are not controlled
However, the sex of the experimenter is rarely considered a biological variable that can influence the results of the experiment, and is usually not taken into
But in order to obtain actionable data to advance the research, Professor Todd Gould's team decided to systematically document these phenomena and investigate the causes
In the new study, they first looked at the mice: in front of the mice were swabs that had been wiped on the skin of women or men (elbow sockets, wrists, and behind the ears), which swabs the mice preferred to touch
The results showed that both male and female mice consistently showed a preference
for swabs with a female odor.
This preference may be olfactory-driven, as it is not observed in mice whose use of zinc sulfate in the nose causes olfactory impairment
In addition, when mice were allowed to choose between swabs moistened with water (control odor) and swabs that had been exposed to female or male skin, the mice showed disgust for swabs that had been exposed to men; Preference was shown for swabs that had been exposed to women
Similarly, mice showed avoidance of T-shirts worn by male experimenters; Female experimenters showed a preference for wearing T-shirts
Professor Todd Gould said that mice have a greater sense of smell and their sensitivity to pheromones (airborne hormones) than humans, so it's not surprising that they respond differently
to various odors.
Next, the researchers assessed the effect
of the experimenter's sex on the mice's response to ketamine administration.
Experiments conducted in multiple laboratories confirmed that mice treated by male experimenters in biosafety cabinets responded
The researchers then investigated several potential factors involved in modulating the ketamine response to determine the mechanisms
behind this behavior in animals.
They eventually found that the disgust and stress sensitivity caused by human male odors are mediated by activation of neurons in the endostatic cortex (EC) projected onto the mouse hippocampus CA1, an area previously thought to be associated with depression; Therefore, activation of the CRF EC-CA1 pathway is an important determinant
of the antidepressant effect of ketamine.
The researchers believe that ketamine combined with CRF receptor agonists may be a new way to treat mood disorders
Subsequently, a female experimenter injected CRF into mice while giving them ketamine in a biosafety cabinet, and the results showed that the mice responded
to ketamine as if they were taking antidepressants.
Polymnia Georgiou, a former postdoc in Todd Gould's lab, said that some people may have higher or lower CRF levels, and if treated with some CRF-related chemicals, perhaps induce the effects of ketamine to make people who do not respond well to ketamine antidepressant treatment
In addition, the antidepressant effect of ketamine usually lasts from 1 to 3 days, but with combined CRF administration, it is possible to prolong the antidepressant effect and make it last longer
These exciting new findings underscore the importance of basic research and lay the groundwork
for future clinical innovations.
The discovery of an unexpected interaction between the mice studied and the sexes of the dosing experimenter highlights the importance of assessing unintended effects
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