Eight years ago, Brian MacVicar discovered that astrocytes—cells that surround nerve cells and all blood vessels in the brain—have a primary role in regulating blood flow within the brain, which provided a new target for potential therapies for stroke, migraine, and vascular dementia. Now he and Hyun Beom Choi, a research associate in his lab, have uncovered a new role for this heroic brain cell: detecting problems in the brain and delivering nutrients to keep brain cells healthy in times of critical need.
The results were published online September 19 in the journal Neuron.
Dr. MacVicar and colleagues found that astrocytes contain a type of sensor, of sorts, that is sensitive to changes in cellular pH in the brain. pH changes naturally in the brain as a result of the transport and utilization of different chemicals and ions, such as calcium or potassium, by cells in order to carry out healthy brain functions.
“Significant changes in pH are not good for the brain,” says Dr. MacVicar, a Canada Research Chair in Neuroscience. “These types of critical conditions can be caused when no sugar—the fuel for brain cells—is available or when brain cells are overly active such as during a seizure, which we then found triggers a cascade of mitigating chemical reactions.”
A key player in these mitigating chemical reactions is the astrocyte. Dr. MacVicar discovered that not only can these cells detect potential problems in the brain, but they can mobilize energy for immediate use even when the brain is seemingly out of its supply of nutrients.
“Essentially, this sensor was reacting to the change in pH by changing its chemical form, which then caused the astrocytes to break down its supply of glycogen into lactate,” explains Dr. MacVicar. “So not only can astrocytes store glycogen, they can also apparently break it down into an alternative, yet usable energy source for brain cells in times of immediate need.”
Glycogen is a large complex strand of glucose molecules. Lactate is the end product of the breakdown of glycogen at low oxygen concentrations.
Future research will examine this mechanism further and see if it could become a potential target for therapies for disorders related to problematic changes in blood brain flow, such as stroke or migraine. As well, other research has shown that some male infertility drugs could potentially affect the central nervous system because they target the same sensor that was found in astrocytes in this study, so future research could examine this connection as well.
This study was funded by grants from the Canadian Institutes of Health Research (CIHR), Fondation Leducq, Heart & Stroke Foundation of Canada, Michael Smith Foundation for Health Research (MSFHR), Alberta Heritage Foundation for Medical Research, National Sciences and Engineering Research Council of Canada (NSERC), and National Institutes of Health.