New Insights Into Brain Fueling Could Lead To Treatments For Stroke, Neurodegeneration

A caller Yale study has revealed that neurons - the energy-hungry cells that link and nonstop activity successful nan brain - are equipped pinch "backup batteries" that footwear successful to support nan encephalon moving during periods of metabolic stress. 

Writing in Proceedings of nan National Academy of Sciences, researchers picture how neurons store their ain glycogen, a shape of sugar that helps neurons stay resilient erstwhile their main power sources falter.

The findings exemplify how neuron cells can adapt their metabolism, researchers say, and could style caller treatments for neurological conditions for illustration stroke, neurodegeneration, and epilepsy, each disorders successful which power nonaccomplishment plays a role. 

"Traditionally, it was believed that glial cells served arsenic 'energy warehouses,' storing glycogen and supplying neurons pinch substance arsenic needed," said co-lead writer Milind Singh, a doctoral student successful compartment biology astatine nan Yale School of Medicine (YSM).

But we now cognize that neurons themselves shop glycogen and tin break it down erstwhile nan unit is on. It's for illustration discovering that your car is simply a hybrid - it's not conscionable reliant connected state stations, it's been carrying an emergency artillery nan full time."

Milind Singh, Doctoral Student, Yale School of Medicine

For nan study, nan investigation team used a microscopic roundworm called Caenorhabditis elegans(C. elegans) - a type of worm commonly utilized successful investigation - and a genetically encoded fluorescent biosensor called HYlight, which glows successful consequence to changes successful glycolysis (the process cells usage to break down sweetener for energy.) 

With custom-built devices, researchers precisely controlled nan level of oxygen nan surviving worms knowledgeable and monitored really neurons responded to power accent successful existent time.

A breakthrough came erstwhile researchers discovered the enzyme PYGL-1, nan worm's type of nan quality glycogen phosphorylase enzyme that converts glycogen into substance for neurons. When researchers removed PYGL-1, nan worm neurons could nary longer ramp up energy during low-oxygen accent conditions; when nan enzyme was specifically restored in neurons, that nonaccomplishment was reversed.

"We discovered that neurons usage 2 different strategies to accommodate to power stress: 1 that's glycogen-dependent, and 1 that isn't," explained co-lead writer Aaron Wolfe, a postdoctoral neuroscience researcher. "The glycogen-dependent pathway is peculiarly captious erstwhile nan mitochondria - one of nan cell's superior power producers - aren't functioning well. In those situations, glycogen serves arsenic a backup strategy to supply power via glycolysis."

The squad coined nan word "glycogen-dependent glycolytic plasticity" (GDGP) to picture this phenomenon. They recovered that GDGP is particularly important erstwhile mitochondrial usability is compromised - such arsenic during hypoxia, a information of constricted oxygen supply. Under these conditions, glycogen serves arsenic a low-cost, rapid-access substance source, helping neurons enactment progressive erstwhile different systems mightiness stall. This metabolic adaptability, known arsenic "glycolytic plasticity," helps neurons support their halfway functions nether stress.

"Our activity challenges nan textbook exemplary of really nan encephalon fuels itself. Neurons are much self-sufficient than we thought," Singh said.

Co-author Daniel Colón-Ramos, the Dorys McConnell Duberg Professor of Neuroscience and Cell Biology at YSM, said nan study supports nan conception of glycogen arsenic an "energy capacitor" successful neurons. 

"Just for illustration successful muscles, this reserve tin buffer accelerated shifts successful power demand," Colón-Ramos said. "That elasticity mightiness beryllium important for really nan encephalon maintains usability and responds to stress.This research reshapes our knowing of encephalon power metabolism and opens caller avenues for exploring really to protect and support neuronal usability successful disease."

Other authors, each from Yale, include Sarah Emerson, a postdoctoral interrogator successful neuroscience; Ian J. Gonzalez, a postgraduate student successful compartment biology; Anjali A. Vishwanath and Anastasia Tsives, post-doctoral researchers successful neuroscience; and Richard Goodman, a research intelligence successful neuroscience.