Neurons store support energy to feed the brain under stress

Summary: New research has discovered that neurons store their own glycogen, acting as “backup batteries” to maintain the functioning of the brain during energy stress. Using advanced worms and biosensors, scientists discovered that neurons can take advantage of glycogen reserves, especially when oxygen or mitochondrial function are limited.

This metabolic flexibility, called “glycogen -dependent glycolytic plasticity”, shows that neurons are more self -sufficient than previously believed. The discovery could inspire new treatments for neurological diseases where energy failure is a key factor.

Key facts:

Neurons store glycogen: unlike long -data beliefs, neurons have their own energy reserves. Stress adaptation: neurons depend on glycogen during low oxygen or mitochondrial dysfunction.

Source: Yale

A new Yale study has revealed that neurons, hungry energy cells that connect and direct activity in the brain, are equipped with “backup batteries” that are activated to keep the brain in operation during periods of metabolic stress.

Writing in minutes of the National Academy of Sciences, researchers describe how neurons store their own glycogen, a form of sugar that helps neurons stay resistant when their main sources of energy hesitate.

The findings illustrate how neurons can adapt their metabolism, researchers say, and can shape new treatments for neurological conditions such as stroke, neurodegeneration and epilepsy, all disorders in which energy failure plays a role.

“Traditionally, it was believed that glial cells served as ‘energy stores’, storing glycogen and supplying neurons with fuel as necessary,” said the co-leader, Milind Singh, a doctoral student in cell biology at the Faculty of Medicine of Yale (YSM).

“But now we know that neurons themselves store glycogen and can decompose it when the pressure is on. It’s like discovering that your car is a hybrid, it not only depends on service stations, but has taken an emergency battery all the time.”

For the study, the research team used a microscopic round worm called Caenorhabditis Elegans (c. Elegans), a type of worm commonly used in research, and a fluorescent biosensor genetically coded genetically called Hylight, which shines in response to changes in glycolysis (process cells use sugar for energy).

With personalized devices, the researchers accurately controlled the level of oxygen that living worms experienced and monitor how neurons responded to real -time energy stress.

There was an advance when the researchers discovered the Pygl-1 enzyme, the version of the human glycogenic phosphorylase enzyme worm that converts glycogen into fuel for neurons.

When researchers eliminated Pygl-1, worm neurons could no longer increase energy during low oxygen stress conditions; When the enzyme was specifically restored in the neurons, that fault was reversed.

“We discover that neurons use two different strategies to adapt to energy stress: one that depends on glycogen and another,” said the co-leader Aaron Wolfe, a postdoctoral neuroscience researcher.

“The glycogen dependent route is particularly critical when mitochondria, one of the main energy producers of the cell, does not work well. In those situations, glycogen serves as a backup system to provide energy through glycolysis.”

The team coined the term “glycolytic glycolytic plasticity” (GDGP) to describe this phenomenon. They discovered that GDGP is especially important when the mitochondrial function is committed, as during hypoxia, a limited supply condition of oxygen.

Under these conditions, glycogen serves as a low -cost fuel source and fast access, which helps neurons stay active when other systems could stop. This metabolic adaptability, known as “glycolytic plasticity”, helps neurons maintain their central functions under stress.

“Our work challenges the textbook model of how the brain is combined. Neurons are more self -sufficient than we thought,” said Singh.

The co-author Daniel Colón-Ramos, a professor of neuroscience and cell biology at Dorys McConnell Dumberg in YSM, said the study supports the notion of glycogen as an “energy condenser” in neurons.

“As in the muscles, this reserve can cushion the rapid changes in energy demand,” said Colón-Ramos.

“That flexibility could be crucial on how the brain maintains the function and responds to stress. This research reforms our understanding of brain energy metabolism and opens new ways to explore how to protect and support neuronal function in the disease.”

Other authors, all from Yale, include Sarah Emerson, a postdoctoral researcher in neuroscience; Ian J. González, postgraduate student in cell biology; Anjali A. Vishwanath and Anastasia Tsives, postdoctoral researchers in neuroscience; and Richard Goodman, a neuroscience research scientist.

On this neuroscience research news

Author: Bess Connolly
Source: Yale
Contact: Bess Connolly – Yale
Image: The image is accredited to Neuroscience News

Original research: open access.
“Glycogen admits glycolytic plasticity in the neurons” of Milind Singh et al. Pnas

Abstract

Glycogen admits glycolytic plasticity in neurons

Glycogen is the largest energy reserve in the brain, but the specific role of glycogen in support for neuronal energy in vivo is not well known.

We established a system in Caenorhabditis Elegans to dynamically investigate glycolytic states in individual cells of living animals by using the light of the glycolytic sensor and determined that neurons can dynamically regulate glycolysis in response to activity or transitory hypoxia.

We perform a RNAI screen and identify that Pygl-1, an orthologist of human glycogen phosphorylase, is required in neurons for glycolytic plasticity.

We determine that neurons use at least two glycolytic plasticity mechanisms: glycogen -dependent glycolytic plasticity (GDGP) and glycolytic glycogen plasticity of glycogen. We discover that GDGP is used in mitochondrial dysfunction conditions, such as transient hypoxia or mutants for mitochondrial function.

We find that the loss of GDGP harms glycolytic plasticity and is associated with defects in the recycling of synaptic vesicles during hypoxia.

Together, our study reveals that, in vivo, neurons can directly use glycogen as a source of fuel to maintain glycolytic plasticity and synaptic function.