” Cells can enter into a dormant state when faced with unfavorable conditions. However, how cells enter into and recover from this state is still poorly understood. Here, we study dormancy in different eukaryotic organisms and find it to be associated with a significant decrease in the mobility of organelles and foreign tracer particles. We show that this reduced mobility is caused by an influx of protons and a marked acidification of the cytoplasm, which leads to widespread macromolecular assembly of proteins and triggers a transition of the cytoplasm to a solid-like state with increased mechanical stability. We further demonstrate that this transition is required for cellular survival under conditions of starvation. Our findings have broad implications for understanding alternative physiological states, such as quiescence and dormancy, and create a new view of the cytoplasm as an adaptable fluid that can reversibly transition into a protective solid-like state”, A pH-driven transition of the cytoplasm from a fluid- to a solid-like state promotes entry into dormancy, Matthias Christoph Munder, Daniel Midtvedt, Titus Franzmann, Elisabeth Nüske, Oliver Otto, Maik Herbig, Elke Ulbricht, Paul Müller, Anna Taubenberger, Shovamayee Maharana, Liliana Malinovska, Doris Richter, Jochen Guck, Vasily Zaburdaev, Simon Alberti https://doi.org/10.7554/eLife.09347.001
Dear Dr Alberti,
Thank you and your colleagues for a fantastic paper. I am not a scientist but I am interested in states of dormancy in cells, in particular in cells of the brain. I know that we must be far away from explaining reversible changes to brain cells involved in reversible dementia or delirium or cognitive impairment, but I have seen a few cases of reversible impairment, I would like to share.
1] an 85 year old lady who was lucid but ,but, since middle age, had poor memory for specific facts. She loved to read up on the news and she remembered what she read, as in general themes; she had trouble remembering the specifics, the little details. This is pretty common, I think, in perfectly normal people. Her kidneys had been slowly deteriorating for a while, but she was doing OK.
After her heart was fixed [balloon angioplasty] and she was put on dialysis [when her kidneys finally failed….she regained the ability to remember in great detail what she read, delighting all she knew with her discussion of politics. It was like she was 20 again. It was unexpected and amazing. This lasted 5 years until her death. It was as if certain brain cells were dormant for decades, and then began to work once more.
2] a 40 year old teacher named Paula woke up suddenly in great distress and anguish. She did not realize it but she had forgotten how to teach, how to cook her regular meals, and how to interact with people. This lasted for over a year and people assumed she was depressed. She wasn’t. She had a very stable delirium. It was extremely unpleasant and unsettling. She was diagnosed with bipolar depression.
We discovered what the problem as she was slowly recovering; her breathing rate was too slow, in health and during illness or exposure to chemicals at her work. In the 1900’s a famous scientist found thousands of patients as incapacitated as Paula. During their delirium they also had too slow breathing. They would occasionally flip into mania and this meant their breathing rate had changed to “too fast” and periodic. These patients would eventually recover their mental and physical health spontaneously; although it could take months, years or decades of insanity and disability. They recovered without brain damage.
During the natural course of manic depressive insanity, spontaneous remission could occur, for long periods of time.
So…it seems that cells involved in higher intellectual functions can recover if organ failure or pH is corrected.
We understand more about Paula’s case because of the scientist who found ventilatory defects in patients who developed depressed mood, mental status and locomotor activity, due to possible unseen respiratory pump failure and hypercapnia. And because Paula and I took a basic first aid class where we unmasked her ventilatory defect……it seems that Paula was born anoxic, swallowed meconium, was resuscitated and transfused and was fine…till she suffered hormonal changes and exposure at the age of 40 and her system failed. [We found out that her respiratory rate did not increase in illness as it should.]
Hypercapnia is a deliriant, a depressant, a euphorias, an intoxicant and an asphyxiant, depending on the levels.
Paula’s lungs are normal and her tidal volumes .5 L per breath.
However, this means she only exchanges 1.5 L of air per minute instead of the assumed 6-8 L.And except for that unique period of illness, she is completely fine and able to teach again.
We know of other cases in which higher brain function was restores once the problem was identified;
3] a girl who became iron deficient [without anemia] due to too much blood loss [heavy menstruation] and was able to recover her normal strength and brain function after getting iron pills and thiamine for a year. [due to her symptoms we thought she was depleted in both nutrients]. She has been fine ever since.
So it seems to us that blood, nutrients, proper circulation of blood and pH of blood and PCO2 of blood can cause long periods of reversible changes to the brain and that certain parts of the brain can remain dormant for a long time till we figure out how to restore them.
When Paula and the iron deficient girl became mentally confused, they were both unable to eat or drink much, their body temperature dropped [mild hypothermia] and their pH was never measured, nor their PCO2. Paula’s pulse oximetry has always been normal but it is not the best tool.
Anyway, the point of all this is that we do not understand when altered mental status is reversible and when it is not.
And this is important in the treatment of serious mental illness and in dementia.
Anyway, this is a far cry from dormancy of yeast cells, but it resonated with me as I watched people lose their minds and then come back to normal.