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Recent research shows us that a specific subcategory of brain cells in male versus female animals responds completely differently to stress. This, the researchers point out, will help understand how men and women are differently affected by mental health issues like anxiety and depression but also physical conditions like obesity and diabetes. It may help us understand the differences in rates of suicidal thoughts versus the incidence of suicide in male versus female veterans. Understanding these sorts of differences in the male vs female response to stress may well lead to therapies that are more accurately targeted for individual patients.

Testing Males and Females Instead of Just Males

The researchers in a recent study of how brain cells respond to stress point out something of concern in how basic science is done. They note that at the very basic level, only male mice are used in mice studies. The idea has always been to have as uniform a population of animals as possible when comparing two or more aspects of a particular test or treatment. These researchers working out of Israel and Germany used male and female mice in a study of the brain’s response to stress.

Testing Males and Females Instead of Just Males

Study of the Brain Under Stress

The study in question looked at the PVN or paraventricular nucleus of the hypothalamus which in a lower level of the brain. They sequenced RNA molecules from individual cells in that area of the brain. They were able to measure how a cell previously exposed to stress reacted to new stress, how a cell responded to new stress, and how there were difference between male and female subjects. This type of study is looking at what is called gene expression. It measured this in 35,000 cells of animal test subjects. They found quite a few differences between male and female subjects.

Male and Female Gene Expression Differences in Acute and Chronic Stress

A particularly strong example of male to female differences in gene expression in response to stress was seen in brain cells called oligodendrocytes. Neurons that carry nerve impulses make up about a third of the brain’s cells. The oligodendrocyte is is a so-called glial cell that provides support for neurons and is important in regulating brain activity. Stress and especially chronic stress caused these cells in males to change how they interacted with surrounding nerves and modify their structure. None of this happened in female test subjects. There were many other differences noted between male and female nerve cells in the study but the change in oligodendrocytes was the most pronounced.

Male and Female Gene Expression Differences in Acute and Chronic Stress

Why Is This Research Important?

This sort of research that looks at both female and male subjects at the basic science level is critical if we are to understand why rates of suicidal thoughts and attempts are higher in female veterans than male veterans. Much research has looked at social and relationship circumstances but has not had available the sort of basic research seen in the recent study. In regard to the great promise of psychedelic medicines for treating PTSD, depression, and substance abuse disorders, we have seen nothing that separates out men versus women in looking at test results, procedures, dosage, or other critical factors. Likewise to the degree that psychedelic treatment of a condition like depression is successful. how effective is it in reducing the incidence of suicide in those patients and are there differences between male and female patients?

Is There a Male to Female Difference in How Psychedelics Affect Neurons?

One of the amazing findings in psychedelic research is that psychedelics cause neurons to create more connections with adjacent nerve cells. We see from the recent animal study that there is a drastic difference under conditions of stress with supporting cells in the brain between male and female test subjects. We have not seen reported any breakdown of male versus female psychedelic treatment patients in regard to brain scan changes and other effects on brain neurons. To the extent that brain scans are showing increased metabolic activity in brain areas stimulated by psychedelics, how much this is the cells noted in this study, the oligodendrocytes, as opposed to the neurons? If there is a difference, how that break down between men and women?

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