A Maynooth team has developed biosensors that can directly monitor brainchemistry in real time. Dick Ahlstrom reports
NUI Maynooth researchers have begun a new research project that investigates the role of "mothering" cells that support brain cells involved in thought processes. Their findings are causing a rethink in the role played by the mothering cells or astrocytes, whose function was little understood.
The work is under way in the bioelectroanalysis laboratory at Maynooth and involves an interdisciplinary team. Dr John Lowry of the department of chemistry won funding for the work from the Health Research Board. He works in collaboration with Dr Marianne Fillenz of the University of Oxford, and this study complements a second project with Prof Nick Rawlins of Oxford backed by Wellcome Trust funding.
The bioelectroanalysis lab has two parts, explains Lowry. One develops biosensors capable of monitoring in real time aspects of the complex biochemistry of the brain. The second is the neurochemistry research unit that carries out the in vivo analysis.
The target of the research is the astrocyte, glial brain cells with a distinctive star-like shape. "Astrocytes are cells that work with neurons in the brain," explains Lowry. "No one was quite sure what they were doing."
Physiologists long assumed that brain cells, in common with most other cell types in the body, simply absorbed the glucose they needed as energy directly from the blood. Glucose fuels all cell types and readily crosses the blood-brain barrier, so astrocytes, although plentiful, were not considered important to brain function or neurochemistry. Nothing could be further from the actual situation. "The whole basis of our research is the evidence over the last five years has started to show astrocytes are very important," says Lowry.
The astrocytes appear to handle glucose on behalf of the neurons. They take up the sugar and hold it until an energy request comes through from the neurons, hence the description of astrocytes as mothering cells that do their job in what Dr Lowry describes as a "compartmented" process. "The picture we have got so far is the neurons connect with the astrocytes by amino acids such as glutamate," says Lowry. This stimulates the astrocytes to release glucose, and as recently discovered, lactate to the neurons.
"Energy metabolism is one of the most important processes in the brain," he says. This is a dynamic process however and studies involving brain slices and other in vitro techniques gave only an incomplete picture of what was happening between the two cell types. This is where the team's biosensors come in. "What we have started to do is use our biosensors to study this."
The sensors involve the use of enzymes that react to target substances produced by these cells. The enzyme is fixed to the surface of a micro probe just 125 millionths of a metre across and if the enzyme reacts an electrical signal is produced. It is an enormous technical challenge to produce these tiny biosensors and the team now has sensors for metabolites including glucose.
The sensors can be connected to animal models to monitor the neurochemistry of this process. "We can now measure these things in real time, which has never been done before," says Lowry. "We have found evidence to support this compartmented model."
This approach also allows the researchers to make use of drugs that can affect astrocyte performance, providing a better understanding of their role and function. "What we want to do now is bring in lactate biosensors and blood flow sensors."
Findings from this research work will be important in understanding both disease processes in the brain and also sudden disruption to blood supply as in stroke. The metabolic trafficking between astrocytes and neurons may play a part in the pathology of these conditions, says Lowry.
"The results will have important implications for how the new brain imaging techniques such as PET (Positron Emission Tomography) are interpreted." PET gives information about chemical processes in tissues but this could be misinterpreted without an understanding of what the chemistry is doing. Understanding disease and brain damage will come later, he believes. "Long-term we may get some results that shed light on these areas as well."