Stress sends immune cells into the brain

As discussed in my book, stress promotes inflammation and immune dysfunction, as well as anxiety. A new and very complete paper from John Sheridan and colleagues at Ohio State University provides evidence that stress also induces an influx of immune cells into the brain, and that this causes anxiety symptoms. They stressed mice by putting an aggressive intruder into their cage for 2 hours each night for 1, 3 or 6 nights. This intruder subdues the residents and makes them subordinate, but does not injure them. Increasing the days of this stress causes and increase in anxiety in the resident mice, as measured in separate assays (not in the presence of an intruder)  by their reluctance to enter the center of an open field and their reluctance to go from a dark box into the light. These are some of the standard ways of measuring anxiety in mice. Increasing the days of stress also causes an increase in immune cells called monocytes in the blood. Using a genetic labeling technique, the investigators went on to show that some of the monocytes then entered the brain, where they became macrophages. Moreover, the parts of the brain where these invading cells are found are the areas known to control anxiety behavior.

This entry into the brain is caused by chemokine signals eminating from the brain itself, and if these signals are blocked, the immune cells do not enter the brain and, importantly, the mice do not display anxiety. That is, if mice who cannot do this chemokine signaling are placed in this highly stressful situation, they do not become anxious and their brains do not display the invading immune cells. The suggestion is then that the stressed brain recruits immune cells to do something that leads to anxiety. This ‘something’ could certainly involve cytokines, as stress increases cytokines in the brain, and cytokines can induce anxiety. But why recruiting macrophages is necessary when the brain’s own cells can produce those cytokines is a mystery. Perhaps the recruited immune cells are also carrying out another function that is helpful (or harmful?) in dealing with social stress. What this might be remains mysterious. It is also not clear how long these invaders remain the brain after the stress is over. Creepy?

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6 Responses to Stress sends immune cells into the brain

  1. With this study http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0048835#pone-0048835-t001 and autism in mind, could one say that gain-of-function in CCR2 ligand would likely make matters worse in such scenarios?

    btw something similar might be going on with peripheral organ inflammation http://www.jneurosci.org/content/29/7/2089

    • Natasa says:

      This finding ‘nicely’ ties up those two above: “Peripheral innate immune challenge exaggerated microglia activation, increased the number of inflammatory CNS macrophages, and prolonged social withdrawal in socially defeated mice.” http://www.ncbi.nlm.nih.gov/pubmed/22386198

      Good news, of a sort, is that beta adrenergic blockade could be helpful here http://www.ncbi.nlm.nih.gov/pubmed/21525267 — especially interesting in the light of (small scale and still early stage etc) findings of propranolol improving various autism symptoms, as demonstrated by University of Missouri team.

      Thank you for your ongoing interest!

  2. John says:

    Histamine clean up? A stressed brain dumps loads of histamine to stay on high alert. Histamine uptake by macrophages may be involved in the clearance of histamine in the local histamine-enriched environment.

  3. Nikki says:

    Have you heard of and have an opinion on mrt (magnetic resonance therapy). It is being used to treat anxiety and autism. Some children are experiencing incredible results. I think anxiety and stress is a huge contributor to my son’s autism symptoms. Wondering if you think something like mrt would be beneficial. It’s being done at the brain treatment center in Orange County California.

  4. There’s been some interesting studies over the last year or so that feature the interconnection between mind and body.

    Meditation and it’s benefits in reducing anxiety has been studied by researchers at Wake Forest Baptist Medical Center, they used MRI …

    “The study revealed that meditation-related anxiety relief is associated with activation of the anterior cingulate cortex and ventromedial prefrontal cortex, areas of the brain involved with executive-level function. During meditation, there was more activity in the ventromedial prefrontal cortex, the area of the brain that controls worrying. In addition, when activity increased in the anterior cingulate cortex – the area that governs thinking and emotion – anxiety decreased.

    http://asdresearchinitiative.wordpress.com/2013/06/05/meditation-anterior-cingulate-cortex-implications-for-autism/

    Harvard Researchers at Massachusetts General Hospital found in their study that …

    “Participating in an eight-week mindfulness meditation program appears to make measurable changes in brain regions associated with memory, sense of self, empathy, and stress.”

    http://asdresearchinitiative.wordpress.com/2012/06/12/harvard-research-retrospective-meditation/

    One wonders whether the next interesting step would be to see if there are physiological changes before and after meditation ?

    Though perhaps meditating mice may be problematic.

    The exciting prospect would be a therapeutic intervention that is portable, undertaken by the ‘patients’ themselves. low cost, without side effects and now beginning to be evidenced based.

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