Roundworm study identifies proteins that could mediate neuron-glia communication as brain ages

The human brain is comprised of two main types of cells, known as neurons and glia. The first are responsible for transmitting electrical and chemical signals, while the latter support and protect neurons.

The communication between neurons and glia is central to the development of the brain and the maintenance of its functions. Past findings suggest that this communication takes place via the binding of ligands (i.e., signaling molecules) to specific proteins or receptors on the surface of a cell.

By studying Caenorhabditis elegans (C. elegans), commonly known as roundworms, researchers at Duke University Medical Center have unveiled a new mechanism that could mediate neuron-glia communications during aging.

Their findings, published in Nature Neuroscience, suggest that heat shock proteins (i.e., proteins that play a role in protecting cells from stress) can act as signaling molecules and mediate communications between neurons and glia as worms age.

“The brain is primarily composed of neurons and glial cells,” Jieyu Wu, first author of the paper, told Medical Xpress.

“In some brain regions, more than half of the cells are glial cells. Numerous studies have shown that neuron–glia interactions play a critical role in brain development and function. This raises an important question: how is neuron–glia communication involved in brain aging?”

Studying neuron-glia communication in live organisms has so far proved challenging, in part due to a lack of animal models that are easy to examine in the lab, but that also mirror some of the mechanisms observed in humans.

C. elegans has been found to be a particularly effective model for studying aging processes, thus Wu and his colleagues decided to select it for their experiments.

“After examining the entire nervous system of C. elegans, we identified the amphid sensory organ as a promising model to investigate neuron–glia communication during aging in vivo,” explained Wu.

“We used chemotaxis assays and calcium imaging to evaluate sensory neuron function. To regulate aging in specific neurons, we employed the auxin-inducible system to deplete key regulatory factors in the aging signaling pathway.”

As part of their experiments, Wu and his colleagues captured the proteins present inside glial cells (i.e., the glial cell-specific proteome) under different conditions in live roundworms. In addition, they looked at how this proteome responded to the aging of neurons.

Subsequently, the researchers used molecular biology techniques to alter some of the worms’ DNA/RNA. This allowed them to label specific proteins, ensuring that they would glow under the microscope and to reduce or entirely silence the activity of specific genes.

“Our study represents the first in vivo instance to show that protein transmission from neuron to glia through extracellular vesicles regulates brain aging,” said Wu.

“Additionally, we revealed that heat shock proteins can act as signaling molecules to mediate neuron-glia communication and influence glial function. These findings offer a new model and open new possibilities for the study of neuron-glia communication.”

This study offers new insight into the intricate neural mechanisms that could contribute to a decline or maintenance of brain function during aging.

The findings gathered by Wu and his colleagues could inspire further research aimed at examining the unique contribution of heat shock proteins to neuron-glia communication in more depth.

“One of my future goals is to investigate the functional significance of extracellular vesicles in brain aging,” added Wu. “I am currently seeking an assistant professor position, with the intention of focusing my research on dissecting the biology of extracellular vesicles in the nervous system and elucidating their roles in brain aging.”

© 2025 Science X Network

The human brain is comprised of two main types of cells, known as neurons and glia. The first are responsible for transmitting electrical and chemical signals, while the latter support and protect neurons.

The communication between neurons and glia is central to the development of the brain and the maintenance of its functions. Past findings suggest that this communication takes place via the binding of ligands (i.e., signaling molecules) to specific proteins or receptors on the surface of a cell.

By studying Caenorhabditis elegans (C. elegans), commonly known as roundworms, researchers at Duke University Medical Center have unveiled a new mechanism that could mediate neuron-glia communications during aging.

Their findings, published in Nature Neuroscience, suggest that heat shock proteins (i.e., proteins that play a role in protecting cells from stress) can act as signaling molecules and mediate communications between neurons and glia as worms age.

“The brain is primarily composed of neurons and glial cells,” Jieyu Wu, first author of the paper, told Medical Xpress.

“In some brain regions, more than half of the cells are glial cells. Numerous studies have shown that neuron–glia interactions play a critical role in brain development and function. This raises an important question: how is neuron–glia communication involved in brain aging?”

Studying neuron-glia communication in live organisms has so far proved challenging, in part due to a lack of animal models that are easy to examine in the lab, but that also mirror some of the mechanisms observed in humans.

C. elegans has been found to be a particularly effective model for studying aging processes, thus Wu and his colleagues decided to select it for their experiments.

“After examining the entire nervous system of C. elegans, we identified the amphid sensory organ as a promising model to investigate neuron–glia communication during aging in vivo,” explained Wu.

“We used chemotaxis assays and calcium imaging to evaluate sensory neuron function. To regulate aging in specific neurons, we employed the auxin-inducible system to deplete key regulatory factors in the aging signaling pathway.”

As part of their experiments, Wu and his colleagues captured the proteins present inside glial cells (i.e., the glial cell-specific proteome) under different conditions in live roundworms. In addition, they looked at how this proteome responded to the aging of neurons.

Subsequently, the researchers used molecular biology techniques to alter some of the worms’ DNA/RNA. This allowed them to label specific proteins, ensuring that they would glow under the microscope and to reduce or entirely silence the activity of specific genes.

“Our study represents the first in vivo instance to show that protein transmission from neuron to glia through extracellular vesicles regulates brain aging,” said Wu.

“Additionally, we revealed that heat shock proteins can act as signaling molecules to mediate neuron-glia communication and influence glial function. These findings offer a new model and open new possibilities for the study of neuron-glia communication.”

This study offers new insight into the intricate neural mechanisms that could contribute to a decline or maintenance of brain function during aging.

The findings gathered by Wu and his colleagues could inspire further research aimed at examining the unique contribution of heat shock proteins to neuron-glia communication in more depth.

“One of my future goals is to investigate the functional significance of extracellular vesicles in brain aging,” added Wu. “I am currently seeking an assistant professor position, with the intention of focusing my research on dissecting the biology of extracellular vesicles in the nervous system and elucidating their roles in brain aging.”

© 2025 Science X Network