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New insights into brain fueling could lead to treatments for stroke, neurodegeneration
A new Yale study has revealed that neurons - the energy-hungry cells that connect and direct activity in the brain - are equipped with "backup batteries" that kick in to keep the brain running during periods of metabolic stress.
Writing in Proceedings of the National Academy of Sciences, researchers describe how neurons store their own glycogen, a form of sugar that helps neurons stay resilient when their main energy sources falter.
The findings illustrate how neuron cells can adapt their metabolism, researchers say, and could shape new treatments for neurological conditions like stroke, neurodegeneration, and epilepsy, all disorders in which energy failure plays a role.
"Traditionally, it was believed that glial cells served as 'energy warehouses,' storing glycogen and supplying neurons with fuel as needed," said co-lead author Milind Singh, a doctoral student in cell biology at the Yale School of Medicine (YSM).
For the study, the research team used a microscopic roundworm called Caenorhabditis elegans(C. elegans) - a type of worm commonly used in research - and a genetically encoded fluorescent biosensor called HYlight, which glows in response to changes in glycolysis (the process cells use to break down sugar for energy.)
With custom-built devices, researchers precisely controlled the level of oxygen the living worms experienced and monitored how neurons responded to energy stress in real time.
A breakthrough came when researchers discovered the enzyme PYGL-1, the worm's version of the human glycogen phosphorylase enzyme that converts glycogen into fuel for neurons. When researchers removed PYGL-1, the worm neurons could no longer ramp up energy during low-oxygen stress conditions; when the enzyme was specifically restored in neurons, that failure was reversed.
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