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When confronted with power stress, why do some individuals develop anxiousness and depressive signs whereas others present resilience? A protein that acts as a cannabinoid receptor and is current within the construction controlling exchanges between the bloodstream and the mind may very well be a part of the reply, in keeping with a research revealed in Nature Neuroscience.
“The protein, called cannabinoid receptor type 1 (CB1), is part of the blood-brain barrier, the dynamic structure that protects the brain by regulating the passage of molecules between the bloodstream and the brain,” explains research chief Caroline Ménard, a professor at Université Laval’s College of Medication and researcher on the CERVO Mind Analysis Heart.
“In the context of chronic social stress, the integrity of this barrier is altered, inflammatory molecules make their way into the brain, and anxiety and depressive symptoms appear.”
CB1 receptors are plentiful in neurons, however they’re additionally present in astrocytes, star-shaped cells permitting communication between the mind’s blood vessels and neurons.
“Astrocytes are an essential component of the barrier,” explains Prof. Ménard. “We noticed that mice resilient to stress had more CB1 receptors in the barrier than mice with depressive-like behavior or mice not exposed to stress. That gave us the idea to investigate the role of astrocytic CB1 receptors in the response to chronic stress.”
The analysis crew first induced a rise in CB1 receptor abundance in mouse astrocytes by growing a viral vector that contained the genetic materials coding for the CB1 receptor in addition to a mechanism that restricted its expression solely to astrocytes. When injected, this virus elevated the degrees of CB1 receptors within the mice’s astrocytes however not of their neurons.
These mice had been then subjected to power social stress. “Each day, for five minutes, they were brought into direct contact with a dominant male. The rest of the time, a transparent divider was placed in the cage. The mice could see their bully without any physical interaction, so it was essentially a psychosocial stress,” says Ménard.
Three weeks after the injections, the extent of CB1 receptors had greater than doubled within the astrocytes of mice within the experimental group.
“In these mice, baseline anxiety levels—those observed in the absence of stress—were reduced, as were symptoms of anxiety and depression-like behaviors induced by social stress. Overexpression of CB1 receptors leads to resilience by promoting vascular health in the brain,” summarizes the researcher.
Different experiments carried out by her crew confirmed that mice that had entry to an train wheel or these given antidepressants additionally had increased ranges of CB1 receptors of their astrocytes.
As well as, examination of human brains from the Douglas-Bell Canada Mind Financial institution in Montreal confirmed the affiliation between CB1 receptors and depressive signs.
“We found that the level of CB1 receptors in astrocytes was lower in people with major depression at the time of death than in people without depression or those treated with antidepressants,” says Ménard.
These outcomes recommend the potential of utilizing molecules able to activating CB1 receptors in astrocytes to cut back anxiousness and depressive signs, and to extend resilience within the face of stress, the researcher suggests.
“The challenge, however, is to limit their effects to astrocytes, because strong and prolonged activation of the same receptors in neurons can have side effects, notably on alertness, anxiety and appetite. Until we find a molecule that acts specifically on CB1 receptors in astrocytes, we can mitigate the negative repercussions of stress by taking advantage of the protective effect of physical activity.”
Extra data:
Astrocytic cannabinoid receptor 1 promotes resilience by dampening stress-induced blood–mind barrier alterations, Nature Neuroscience (2025). DOI: 10.1038/s41593-025-01891-9
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